FitSugar

Would You Pay For an Allergy-Free Hotel Room?

FitSugar — Tue, 23 Dec 2008 12:00:24 -0800

Since I have allergies, traveling away from my trigger-free home can be frustrating and uncomfortable. Not only do I have to deal with cats on the plane, but new locations mean new plant pollens, dust, and mold. So what's an allergy-suffering girl to do?

Some hotels, including Marriott, are offering allergy-free hotel rooms, using a system called Pure Room. Visitors can opt for specially treated rooms with bedding, carpets, and AC systems free from contaminants. The rooms come with air purifiers to make breathing easier, and the mattresses and pillows are encased in covers to fend off dust mites. Also, the carpets and upholstery are treated with ozone shock treatment to kill mold and bacteria.

Since it's estimated that one third of people who stay in a hotel end up having an allergic reaction, this is a brilliant and much-needed improvement. The Pure Room isn't available at all Marriott Hotels, but you can call ahead to find out. Each room is only about $20 more a night, so tell me, would you pay more for an allergy-free room?

Source

You Asked: Too Many Trips to the Ladies Room?

FitSugar — Tue, 25 Aug 2009 10:00:20 -0700

Dear Fit,
I drink tons of water, and probably go through four 32-ounce Nalgene bottles within the eight hours I am at the office, so I assume that's the reason. I'm wondering if this is bad for me? I go to the "ladies" at least once an hour to pee, and the guys in my office think it's way too often.
- Fearful of Over Watering

Women have smaller bladders than men, so that's why we tend to visit the ladies room more often. Is it possible to have to go too often? To find out keep reading

Bipolar disorder

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17. Risperidone (an atypical antipsychotic) and lithium (a mood stabilizer) are the two drugs currently approved for treating pediatric patients with bipolar disorder.

Drug Warnings

Olanzapine (Zyprexa, Symbex) causes a greater risk for high blood sugar than other atypical antipsychotics, according to updated information added to the drug’s warning label. Olanzapine also causes weight gain and can increase the risk for unhealthy cholesterol levels.
All atypical antipsychotics increase the risk for diabetes. Patients who take these drugs should receive regular screenings for changes in blood sugar levels. Patients should also have their cholesterol levels monitored.

Bipolar Disorder in Children and Adolescents

Diagnoses of bipolar disorder in children have increased 40-fold in the past decade, according to an analysis in the Archives of General Psychiatry. There is debate whether bipolar disorder in children was under-diagnosed in the past or is being over-diagnosed now.
Bipolar symptoms in children differ from those of adults, with some symptoms overlapping with behavioral and conduct disorders. New guidelines from the American Academy of Child and Adolescent Psychiatry (AACP) caution that a diagnosis of bipolar disorder must be carefully made, especially considering the risks associated with drug therapy. The AACP also advises that there are currently no established criteria for diagnosing bipolar disorder in preschoolers.

Bipolar Depression

The antidepressants bupropion (Wellbutin) and paroxetine (Paxil) do not increase the risk for mania, but neither do they help ease depression any more than mood stabilizers, suggests a 2007 study in the New England Journal of Medicine.
Intensive psychotherapy in combination with medication can help improve depression outcomes, indicates a 2007 study in the Archives of General Psychiatry.

Introduction

Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:

Periods of mania with exaggerated euphoria, irritability, or both
Episodes of depression

Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.

Bipolar disorder is classified according to the pattern and severity of the symptoms as bipolar disorder I, bipolar disorder II, or cyclothymic disorder. Patients with one type may develop another. Nevertheless, they are distinct enough to merit separate classifications, and some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.

Bipolar Disorder I. Bipolar disorder I is characterized by at least one manic episode, with or without major depression, that lasts for at least 7 days. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.

Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.

Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by episodes of predominantly depressive symptoms, with occasional episodes of hypomania, which last for at least 4 days. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.

Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.

Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures, while bipolar II patients were "sunnier.")

The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.

Symptoms of the Depression Phase. The symptoms of depression experienced in bipolar disorder are almost identical to those of major depression, the primary form of unipolar depressive disorder. They include:

Sad mood
Fatigue or loss of energy
Sleep problems such as insomnia, excessive sleeping, or shallow sleep with frequent awakenings
Appetite changes
Diminished ability to concentrate or to make decisions
Agitation or markedly sedentary behavior
Feelings of guilt, pessimism, helplessness, or low self-esteem
Loss of interest or pleasure in life
Thoughts of, or attempts at, suicide

Distinguishing Between Unipolar and Bipolar Depression. It is often difficult to differentiate between unipolar and bipolar depression, particularly in patients with bipolar II disorder. They may differ in the following ways:

Bipolar depression typically lasts 2 - 3 months -- not as long as in major depression (although left untreated some bipolar disorder episodes can last 6 - 12 months or longer).
People with unipolar depression can still experience a variety of other moods, but none meet the criteria for a manic state.
Depressive symptoms in those with bipolar disorder tend to vary. For example, some patients experience increased sleep, gain weight, and feel a heaviness and slowness in their bodies. Other patients with bipolar depression experience impaired sleep, but unlike patients with unipolar depression, they do not feel sleepy the next day.
Bipolar depressive episodes tend to develop more gradually than do those caused by major depression.

Symptoms of the Acute Manic Phase. The acute pure manic phase is always characterized by mood elevation, presented in the following ways:

Exaggerated euphoria (a feeling of great happiness or well-being)
Irritability
Both euphoria and irritability

The episode lasts for at least few days but, in some cases, the episode may last weeks or even months and may be severe enough to require hospitalization.

Other symptoms must also be present to make a diagnosis. Some mental health professionals use the mnemonic device DIGFAST to identify them. In general, for a diagnosis of mania, a patient must have experienced either euphoria with three DIGFAST symptoms or irritability with four of these symptoms:

D. Distractibility. This is the most common symptom, and it is usually characterized by the inability to pay attention to any activity for very long.
I. Insomnia in mania typically means having high energy and requiring less sleep. (This differs from insomnia in depression, in which the patient has low energy plus an inability to sleep.)
G. Grandiosity. Patients with this symptom have an inflated sense of themselves, which, in severe cases, can be delusional. Close to 60% of all manic patients experience feelings of being all-powerful. Sometimes they feel that they are godlike or have celebrity status.
F. Flight of ideas. Thoughts literally race.
A. Activity. The patient may show an increase in intensity in goal-directed activities, which are related to social behavior, sexual activity, work or school.
S. Speech. The patient may talk excessively.
T. Thoughtlessness. Excessive involvement in high-risk activities is present (such as unrestrained shopping, promiscuity). Mood disturbance may be severe enough to damage one's job or social functioning or one's relationships with others. Some patients require hospitalization to prevent harm to others or to themselves.

Some patients with bipolar I may experience psychotic symptoms, including thought disorders, hallucinations, and catatonia (a state in which the patient goes into a stupor for long periods, which may give way to short periods of extreme excitement).

Hypomania. With hypomania the symptoms of mania are milder and of shorter duration (but they last at least 4 days). They do not affect social or work life as dramatically.

Mixed Mania State Symptoms. Mixed mania (also called mixed episodes or dysphoric mania) are manic episodes that also have a depressive component. In such a state, mania is present to a significant degree, but depression is present most of the day and nearly every day. Such mixed symptoms occur for at least a week.

Depressive Mixed State Symptoms. Depressive mixed state is characterized by major depression as the primary emotional state with manic features (such as irritability, distractibility, and racing thoughts). Such patients may receive an inaccurate diagnosis of unipolar depression.

Risk Factors

Between 1 - 2 million Americans may suffer from bipolar disorder. Researchers estimate that about 1% of Americans experience bipolar disorder during the course of their lifetime, but some studies indicate that prevalence may be as high as 4%. There is differing opinion on how to diagnose and categorize bipolar symptoms, which affects these estimates. The majority of people with bipolar disorder also have other psychiatric disorders, particularly anxiety and substance abuse.

Bipolar disorder affects both sexes equally, but there is a higher incidence of rapid cycling, mixed states, and cyclothymia in women. Early-onset bipolar disorder tends to occur more frequently in men and it is associated with a more severe condition. Men with bipolar disorder also tend to have higher rates of substance abuse (drugs, alcohol) than women.

Bipolar disorder frequently occurs within families, although genetic factors account for only about 60% of cases. Family members of patients with bipolar disorder also have a higher than average incidence of other psychiatric problems. They include schizophrenia, schizoaffective disorder, anxiety disorders, ADHD, and major depression.

Causes

No single cause may ever be found for bipolar disorder. Instead, a combination of biologic, genetic, and environmental factors appears to trigger and perpetuate the chemical imbalances in the brain that shape this complex disorder. Biologic factors observed or considered in bipolar disorder, as detected by use of imaging scans and other tests, include:

Oversecretion of cortisol, a stress hormone
Excessive influx of calcium into brain cells
Abnormal hyperactivity in parts of the brain associated with emotion and movement coordination
Low activity in parts of the brain associated with concentration, attention, inhibition, and judgment
A superfast "biologic clock"

The so-called biologic clock is a tiny cluster of nerves called the supra chiasmatic nucleus, or SCN. The SCN is located in the center of the brain in the hypothalamus region. It regulates a person's circadian rhythm, the daily cycle of life, which influences sleeping and waking.

The genetics of bipolar disorder are the most intensively studied of all psychiatric diseases. Multiple genes, involving several chromosomes, have been linked to its development. Bipolar disorder also may share these genetic factors with other disorders, including schizophrenia, epilepsy, and panic disorder. It is not clear if some of these disorders are variations of a single disease or separate disorders.

Bipolar Disorder and Schizophrenia. Researchers have been investigating whether common biologic factors are involved with schizophrenia, severe bipolar disorder, and other psychoses. Schizophrenia and bipolar disorder often show up in the same family. Researchers are identifying a number of common genetic and biologic pathways that they both share. Bipolar Disorder and Epilepsy. Neurotransmitters called gamma aminobutyric acid (GABA) and norepinephrine have been implicated in mania:

GABA helps prevent nerve cells from over-firing
Norepinephrine is a hormone that involves stress

Some research has associated similar biologic mechanisms in patients with epilepsy and bipolar disorder. As in epilepsy, the more episodes a bipolar disorder patient experiences early in the course of the disease, the more frequent and severe later episodes will be. Antiseizure drugs, in fact, can play an important role in the treatment of bipolar disorder.

Panic Disorder and Bipolar Disorder. Researchers are also studying the common biologic and genetic factors between panic disorder and bipolar disorder. While specific genes have not yet been identified, some researchers studying these illnesses now believe that they may represent different forms of a shared, complex condition.

Prognosis

Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes. Patients with the disease may experience symptoms in very different ways. A typical bipolar disorder patient averages 8 - 10 manic or depressive episodes over a lifetime. However, some people experience more and some fewer episodes.

Typical Bipolar Cycles. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression are neither regular nor predictable. Many patients experience mixed mania, or a mixed state, in which both mania and depression coexist for at least 7 days.

Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.

Differences Between Children and Adults. Research suggests that symptoms of bipolar disorder in children and adolescents differ from those of adults. While adults with bipolar disorder usually have distinct and persistent periods of mania and depression, children with bipolar disorder fluctuate rapidly in their mood and behavior. Mania in children is characterized by irritability and belligerence whereas adults tend to experience euphoria. Children with bipolar depression are frequently angry and restless, and may have additional mood and behavioral disorders such as anxiety, attention deficit hyperactivity disorder, conduct disorder, and substance abuse problems.

Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.

Bipolar disorder usually first occurs between the ages of 15 - 30 years, with an average age of onset at 25 years. However, bipolar disorder can affect people of all ages, including children. Bipolar disorder that occurs late in life often accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.

Patients with bipolar disorder, especially type II or cyclothymic disorder, have frequent episodes of major depression. Anxiety disorders also commonly coexist in these patients. For example, the occurrence of panic disorder in patients with bipolar disorder is 26 times that of the general population. Patients with bipolar disorder, particularly those with type II, are also subject to phobias. In one study, the presence of anxiety disorders was also associated with longer and more severe bipolar depressive episodes and with a higher risk for suicide.

Symptoms of bipolar disorder in children are often confused with attention-deficit hyperactivity disorder (ADHD). Furthermore, the two conditions can coincide. In one study, 65% of adolescents with bipolar disorder met criteria for ADHD. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some researchers believe that many of these disorders may actually be variations of a single disease.

The risk for suicide is very high in patients who suffer from bipolar disorder and who do not receive medical attention. Between 10 - 15% of patients with bipolar disorder I commit suicide, with the risks being highest during episodes of depression or mixed mania (simultaneous depression and mania). Some studies suggest that the risk for suicide in patients with bipolar disorder II is even higher than it is for those with bipolar disorder I or major depressive disorder. Patients who also suffer from an anxiety disorder are also at greater risk for suicide. (Rapid cycling, although a more severe variation of bipolar disorder, does not appear to increase the suicide risk in patients with bipolar disorder.)

Many pre- and early adolescent children with bipolar disorder are more severely ill than are adults with the disease, and the risk for suicide is high. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.

Studies suggest that patients with bipolar disorder may have varying degrees of problems with short- and long-term memory, speed of information processing, and mental flexibility. Such problems persist even between episodes. They tend to be more severe when a person has more manic episodes. Medications used for bipolar disorder could be responsible for some of these abnormalities, although some evidence suggests that such traits may have a biologic basis. These mental difficulties may make it harder for these patients to comply with medications or to participate in complex psychotherapies.

A small percentage of bipolar disorder patients demonstrate heightened productivity or creativity during manic phases. More often, however, the distorted thinking and impaired judgment that are characteristic of manic episodes can lead to dangerous behavior, including:

Spending money with reckless abandon, causing financial ruin in some cases
Angry, paranoid, and even violent behaviors
Openly promiscuous behavior

Such behaviors are often followed by low self-esteem and guilt, which are experienced during the depressed phases. During all stages of the illness, patients need to be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.

Cigarette smoking is prevalent among patients with bipolar disorder, particularly those who have frequent or severe psychotic symptoms. Some experts speculate that, as in schizophrenia, nicotine use may be a form of self-medication because of its specific effects on the brain.

Up to 60% of patients with bipolar disorder abuse other substances (most commonly alcohol, followed by marijuana or cocaine) at some point in the course of their illness.

The following are risk factors for alcoholism and substance abuse in patients with bipolar disorder:

Having mixed-state episodes rather than ones of pure mania
Being a man with bipolar disorder

Patients do not manifest their negative behaviors (such as spending sprees or even becoming verbally or physically aggressive) in a vacuum. They have a direct effect on others around them. It is very difficult for even the most loving of families or caregivers to be objective and consistently sympathetic with an individual who periodically and unexpectedly creates chaos around them.

Many patients and their families find it difficult to accept that these episodes are part of an illness and not simply extreme, but normal, characteristics. Such denial is often strengthened by patients who are highly articulate and deliberate, and who can intelligently justify their destructive behavior, not only to others, but also to themselves.

Family members may also feel socially alienated by the fact of having a relative with mental illness, and feel forced to conceal this information from acquaintances.

The economic burden of bipolar disorder is significant. It is estimated that the disorder costs the U.S. workplace about $14.1 billion annually in lost productivity, mostly due to poor functioning on the job. According to a 2006 study sponsored by the U.S. National Institute of Mental Health, bipolar disorder accounts for twice as much lost productivity as major depressive disorder (MDD), despite the fact that MDD is more prevalent. Each worker with bipolar disorder loses about 66 workdays a year compared with 27 workdays a year for workers with MDD. Research suggests that bipolar disorder’s depressive episodes impair productivity more than its manic episodes.

People with mental illness have a higher incidence of many medical conditions, including heart disease, asthma and other lung problems, gastrointestinal disorders, skin infections, diabetes, hypertension, migraine headaches, hypothyroidism, and cancer. Patients with bipolar disorder are also less likely to receive medical care than people without mental disorders. Substance abuse, including smoking, alcoholism, and drug abuse, also contributes to many of these problems as well as reduced access to care. Medications used for bipolar disorder can also increase the risk for medical problems.

However, people with bipolar disorder and other mental illness have a higher risk for a number of these conditions independent of these factors.

Diabetes. Diabetes is diagnosed almost three times more often in people with bipolar disorder than it is in the general population. Many patients with bipolar disorder are overweight, with about 25% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.

High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.

Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. Patients with bipolar II suffer from migraine more frequently than patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.

Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.

Diagnosis

Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.

When making a diagnosis of bipolar disorder, it is important that the doctor rule out other conditions that may be causing symptoms of bipolar disorder.

Distinguishing Mania from Normal Euphoria or Joy. A major difficulty with a diagnosis of bipolar disorder is the tendency for a patient to be unable to recognize his or her own condition, particularly when in the manic state. The patient often denies their symptoms, which may be perceived as positive feelings. The doctor should take a careful and complete history of any and all episodes of depression, mania, or both. Hypomania, the less severe variant of mania, may be particularly difficult to distinguish from normal joy or euphoria. It can often be distinguished by the following characteristics:

Hypomania persists for at least 4 days
Patients with hypomania are easily distracted and overly talkative
Patients with hypomania have difficulty functioning

Distinguishing Unipolar from Bipolar Depression. People with bipolar disorder are more likely to seek help because of a depressive episode and may not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.

Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.

A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.

Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.

Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:

The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
A flat emotional expression, with no variability in the voice among people with schizophrenia
People with bipolar disorder are typically very expressive

Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.

Other Causes of Mood Swings. Other conditions that can cause mood swings include:

Thyroid disorders
Adrenal disorders (Addison's disease or Cushing syndrome)
Vitamin B12 deficiency
Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease

Patients should be tested for drugs or alcohol if the doctor suspects that they have been using these substances. Blood tests for thyroid function should also be performed.

Noninvasive imaging tests of the brain using magnetic resonance imaging (MRI) and positron-emission tomographic (PET) scans are being evaluated in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments. However, imaging tests do not currently play a role in diagnosing bipolar disorder.

The number of children diagnosed with bipolar disorder has increased dramatically during the past decade. Psychiatrists debate whether bipolar disorder was formerly under-diagnosed in children or whether it is being over-diagnosed now. Part of the controversy concerns the diagnostic criteria used for children and adolescents. Some bipolar symptoms, such as irritable mania, share characteristics with common childhood anger outbursts or behavioral disorders such as conduct disorder and attention deficit hyperactivity disorder. In addition, many children with bipolar disorder also have behavioral and developmental disorders. These overlapping conditions can complicate diagnosis.

The American Academy of Child and Adolescent Psychiatry (AACP) recommends that doctors use specific screening questions to diagnose bipolar disorder. These questions are designed to evaluate periods of mood changes associated with sleep disorders and restlessness. Doctors should also ask about family histories of mood disorders. The AACP cautions that the validity of diagnosing bipolar disorder in children younger than 6 years old has not been established.

Bipolar disorder is treated with powerful psychiatric drugs that can cause serious side effects. It is very important to make sure that a child’s symptoms are due to bipolar disorder, rather than emotional or behavioral issues, before prescribing these medications.

Treatment

Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:

Treat and reduce the severity of acute episodes of mania or depression when they occur
Reduce the frequency of episodes
Avoid cycling from one phase to another
Help the patient function as best as possible between episodes

The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.

Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this “collaborative care” model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.

The treatments for bipolar disorder, while very effective, pose some specific challenges for the patient:

Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a patient is responding to treatment or naturally emerging from a bipolar phase.
A patient with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
The patient is likely to need more than one medication during the course of the disease. This increases the risk for distressing side effects. Noncompliance is common.
Patients often have more than one medical problem and need different drugs to treat each condition. Such medications may interact with drugs used to treat bipolar disorder or increase side effects. For example, children with bipolar disorder have a higher risk for attention deficit-hyperactivity disorder, which is treated with stimulants that can complicate bipolar treatment.
Family members who have not been educated about the disorder may interfere with the treatment.
Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
Treatments may be costly.

The following are the treatment options for most patients with bipolar disorder, depending on the bipolar disorder phase or episode. Patients should understand that, even with aggressive therapy, either mania or depression recurs in almost three-quarters of patients.

Drugs Used in Bipolar Disorder. Mood stabilizing drugs are the mainstay for patients with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used.

Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many patients with other bipolar subtypes.
Antiseizure Drugs. Valproate (valproic acid) carbamazepine (Tegretol, Carbatrol, Equetro), oxcarbazepine (Trileptal), and lamotrigine (Lamictal) are the most established antiseizure drugs. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify).

Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.

Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.

Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.

Step 1. Determine the Need for Hospitalization and Eliminate Triggers. The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods.

Patients often require hospitalization at the onset of acute mania. The need for hospitalization depends on a number of factors:

Whether the patient is at risk for suicide or for harming others
The availability of social and emotional support at home

Step 2. Control Symptoms of Acute Manic with a Mood Stabilizer. Doctors often try different drugs to control a manic episode. If a current drug does not work well, another type of drug may be added or substituted. It may take several weeks for a mood stabilizer to take effect, and other drugs may be needed.

The following is an example of a stepped approach recommended by some experts:

Initiating a mood-stabilizing drug is the critical first step. Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective in 60 - 80% of all hypomanic and manic episodes. Carbamazepine is usually used in place of valproate to treat patients with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the patient does not respond to a single drug.
If the patient does not respond fully within a week, atypical antipsychotics may be added to one or more mood stabilizers. Atypicals include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), apriprazole (Abilify), and ziprasidone (Geodon). Clozapine (Clozaril), the oldest atypical drug, also works well but it is not generally used because of its potential for severe side effects and the need for weekly monitoring of white blood cell counts.

Step 3. Addition of Other Treatments. Other treatments may be added to speed recovery, treat any psychosis, and achieve remission. They include:

Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol), may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.

Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:

When side effects are intolerable
When the patient does not respond to the maximum dose
When the patient improves and recovery is sustained

In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.

Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.

Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are very difficult and patients who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 - 3 months.

Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.

If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).

Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.

An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the Food and Drug Administration (FDA) approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax was the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.

Other Treatments. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches.

The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling:

Antidepressants, particularly SSRIs, may prompt rapid cycling and should be tapered off.
Lithium or valproate is a first-line treatment for rapid cycling.
Lamotrigine is an alternative treatment for rapid cycling.
Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
Electroconvulsive therapy can be useful in emergency situations.

In addition, other measures should be taken:

Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
Patients should avoid exposure to bright light.
All efforts should be made to help the patient sleep normally.

Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long maintenance therapy. This usually involves mood-stabilizing drugs:

Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also used as a first-line drug for treating depressive episodes.
Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.

The general recommendations for maintenance therapy with lithium are as follows:

The earlier lithium is started in the disease process, the better. Studies suggest that patients on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates due to an increased suicide risk.
Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.

Information on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy.

Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:

In women who discontinue lithium during pregnancy, the chance for recurrence of bipolar disorder is the same as in non-pregnant women, which is over 50%.
Pregnant women with bipolar disorder are at particularly high-risk for recurrence in the period after childbirth. In one study, symptoms recurred in 74% of women after delivery, and another 20% were hospitalized within 90 days after giving birth. The risk for depressive or mixed states is particularly high.

Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:

Lithium can pass through the placenta and affect the fetus. When possible, patients should avoid taking lithium during pregnancy, especially during the first 3 months. Studies report that lithium use during the first trimester may cause heart defects and thyroid problems in the baby. If taken immediately before childbirth, lithium can also cause muscle weakness and drowsiness in newborn infants. Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 - 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
The antiseizure drugs valproate and carbamazepine both greatly increase the risk for physical malformations, developmental delay, and spina bifida in babies. They appear to have minimal effect on breastfeeding, however. Lamotrigine can cause cleft lip and palate birth defects if taken during the first trimester.
Small studies have suggested that the atypical antipsychotic olanzapine does not increase the risk for birth defects. However, it does pose a great risk for excess weight gain that could be unhealthy during pregnancy. Less is known about the effects of other atypical antipsychotics during pregnancy.

Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor.

Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.

Until recently, lithium was the only drug approved for treating bipolar disorder in children (age 12 years and older). In 2007, the FDA approved the atypical antipsychotic risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17.

Lithium is generally used as the first-line treatment, with valproate and risperidone (or other atypical antipsychotics) as alternatives. If treatment with a single drug does not work, a combination of drugs may be used.

Lithium and valproate are the drugs most studied in children and adolescents. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination, weight gain (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate). Side effects of risperidone may include drowsiness, fatigue, increased appetite, nausea, dizziness, dry mouth, tremor, and rash.

Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.

Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. Electroconvulsive therapy (ECT) may benefit adolescents with bipolar I disorder who suffer severe episodes of mania or depression and who have not been helped by medication.

Medications

Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:

Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
It helps to prevent relapses.
It helps psychosocial functioning.
It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
It works well for most patients even if they have discontinued taking it and wish to restart treatment.

Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:

Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.

In addition to drugs, several factors may affect lithium levels:

Seasonal change -- lithium levels may be higher in summer.
Menstrual cycle -- lithium levels may drop during the premenstrual phase.
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.

Lithium Toxicity. Evidence of moderate toxicity include:

Trembling hands
Nausea
Increased urine output
Blurred vision
Some loss of coordination

Severe reactions occurring at higher blood levels, include:

Vomiting
Convulsions
Uncontrolled jerky movements in arms and legs
Stupor
Coma

Very high blood levels of lithium can be fatal. If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:

Patients are given fluids and drugs to increase excretion of lithium salts.
Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:

An unpleasant taste in the mouth
Hair loss
Skin eruptions that can resemble acne and make psoriasis worse
Low thyroid function
An increased risk for diabetes
A blunted sexual drive
Dulled emotions and lack of mental clarity
Memory loss
Lack of motor coordination
Increased sensitivity to light

In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

The risks associated with these drug interactions are very low, but caution is needed.

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.

Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.

Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.

Antiseizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. These drugs may be an alternative for patients (especially substance abusers) who do not tolerate or respond to lithium. They also may be used in combination with lithium, atypical antipsychotics, or other drugs.

Standard Antiseizure Drugs.

Valproate (Depakote), also called valproic acid or divalproex, is now a first option for many bipolar disorder patients. It works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Valproate also helps migraine headaches, a common problem among patients.
Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers.
Carbamazepine (Epitol, Tegretol), a standard alternative antiseizure drug used for mood stabilizing, is usually the second anti-seizure medication of choice. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Another drug, oxcarbazepine (Trileptal), is similar to carbamazepine.
Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.

General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:

Gastrointestinal problems such as nausea, vomiting, and heartburn
Headaches
Visual disturbances
Ringing in the ear
Hair loss
Weight gain (a significant problem with valproate)
Agitation
Odd movements
Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
Birth defects when taken by pregnant women
Cognitive impairment and symptoms of Parkinson's disease

Very serious side effects are possible. Stevens-Johnson syndrome (SJS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. The risk of serious skin reactions is 10 times higher for patients of Asian ancestry than Caucasians. The FDA recommends that people of Asian ancestry get a genetic test before starting carbamazepine to determine if they are at risk for this side effect.

Other serious side effects, also rare, may include liver damage, convulsions, coma, and pancreatitis.

Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon).

Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Paliperidone (Invega), which is chemically related to risperidone, was approved in 2007 for treatment of schizophrenia but has not yet been approved for bipolar disorder.
Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
Clozapine has not been approved for treatment of bipolar disorder, but has shown promise in investigational studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis).

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include:

Nasal congestion or runny nose
Drooling
Dizziness
Headache
Drowsiness -- however, these drugs may also cause restlessness and insomnia.
Constipation
Rapid heart beat
Difficulty urinating
Skin rash
Increased body temperature
Confusion, short-term memory problems, disorientation, and impaired attention
Weight gain -- risk is highest with clozapine and olanzapine, lowest with aripiprazole and ziprasidone

More serious risks include:

Diabetes (See Diabetes Risk and Atypical Antipsychotics)
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
Seizures
Heat stroke
Sudden drop in blood pressure (hypotension)
A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
Extrapyramidal side effects, which are lack of motor coordination and involuntary movements
Cataracts and worsening of any existing glaucoma
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.

Diabetes Risk and Atypical Antipsychotics. In 2003, the FDA requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:

Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They may trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. Another antidepressant, venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.

Side effects of SSRIs include:

Nausea and gastrointestinal problems, which usually wear off over time
Agitation, insomnia, mild tremor, and impulsivity
Dry mouth, which can increase the risk for cavities and mouth sores
Headache
Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Other Treatments

Electroconvulsive therapy (ECT) is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.

Research suggests ECT may be particularly beneficial for:

Patients who need immediate stabilization of their condition and who cannot wait for medications to work
Most patients with mania -- especially elderly patients with severe mania
Patients who suffer suicidal thoughts and guilt during the depressive phase
Pregnant patients
Patients who cannot tolerate drug treatments
Patients with certain types of heart problems
Young patients

In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.

The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:

A muscle relaxant and short-acting anesthetic are given to the patient.
A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
The response to ECT is usually very fast, and the patient often needs less medication afterward.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded.

Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:

Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
Causing various hormonal changes, particularly with thyroid-related hormones.
Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory).

Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.

Transcranial Magnetic Stimulation. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.

Therapy and Lifestyle Changes

Psychotherapy is an important addition to medication. Many approaches are proving to be very useful. Trained mental health professionals can:

Educate patients about bipolar disorder and its treatments
Teach patients to recognize and manage early warning symptoms of imminent manic or depressive episodes
Help them comply with drug regimens
Monitor the patient's on-going status
Intervene early in manic and depressive episodes to reduce the severity of the attack

In addition, psychotherapy can help patients:

Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
Cope with feelings of guilt and remorse that occur after manic episodes
Deal with feelings of imperfection and despair

Therapists trained in cognitive-behavioral therapy (CBT) may be particularly helpful for many patients. CBT is a structured, conscious method that aims to help a patient recognize negative thoughts and behavioral patterns and to change them. CBT is known to be helpful for other mood disorders, including depression and anxiety, and some studies suggest that it benefits bipolar disorder patients as well. For example, in one recent study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.

Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:

Recognize manic episodes before they become full-blown and change behaviors during an episode
Cope with depression by developing behaviors and thoughts that may help offset the negative mood

It is very important that partners, family members, or both be involved in therapy. CBT can help them learn how to accept the condition, the need for medications, and how to protect themselves and the patient financially during manic episodes. In fact, one study indicated that when a spouse of a patient learned ways of coping with the illness, the partner's chances of sticking to a prescribed treatment improved.

Supporting the Patient. Recommendations for supporting the patient include:

Create a treatment contract as a first step. In this contract, the patient and family agree to specific steps for maintaining emotional stability. If such measures fail, all parties agree on further actions to be taken during an acute episode, including requests for hospitalization.
Be supportive. Unlike relatives of patients with alcoholism who may be encouraged to get tough, relatives of patients with bipolar disorder must be strongly supportive because of the high risk for suicide with this disorder. Simply listening attentively and being empathic can help.
Get the patient to comply with treatment, even if it means threatening a hospitalization if the patient fails to comply.
Have ready a hotline number or the telephone number of a psychiatrist authorized to commit the patient. The doctor should be willing to facilitate commitment if a patient becomes violent or the family is on the verge of collapse.
Don't feel guilty and don't make the patient feel guilty. Bipolar disorder results from an imbalance of chemicals in the brain and not from anyone's fault.

Support for the Family. Unfortunately, actions that support a bipolar disorder patient may not be intuitive, and they take their toll. Loved ones must also care for themselves or they may also follow a path to severe depression. They should to boost energy and reduce stress through:

Exercise
Meditation
Relaxation techniques
Holidays away from the patient
Involvement in hobbies
Involvement in support groups, Internet resources with chat rooms, and message boards for bipolar disorder caregivers

Interpersonal problems (such as family disputes) and disruptions in daily routines or social rhythms (such as loss of sleep or changes in meal times) may make people with bipolar disorder more susceptible to new episodes of their illness. A form of psychosocial treatment called interpersonal and social rhythm therapy (IPSRT) focuses on maintaining a regular schedule of daily activities to reduce these potential triggers and improve emotional stability. Patients also learn how to avoid problems with personal relationships. Preliminary evidence suggests that IPSRT combined with drug therapy works better than medication alone. A 2-year study of patients with bipolar 1 disorder indicated that IPSRT may help prevent new manic episodes.

Exercise. Exercise is an important part of treatment, particularly in helping manage weight gain. It also helps increase feelings of well-being.

Sleep Management. Good sleep hygiene is particularly important for patients. One study reported that techniques used to enforce healthy sleep helped reduce mood cycling.

Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. People with bipolar disorder should be sure to maintain a regular healthy diet. They may need to restrict calories if they are on medications that increase weight.

Some research indicates that consumption of omega-3 polyunsaturated fatty acids found in oily fish (such as mackerel, sardines, salmon, and bluefish) may help reduce the symptoms of a variety of mental illnesses, including bipolar disorder. Researchers are investigating the effects of eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) supplements for patients who have not responded to other treatments.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.bpkids.org -- Child & Adolescent Bipolar Foundation
www.dbsalliance.org -- Depression and Bipolar Support Alliance
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

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Review Date:
12/25/2007
Reviewed By:
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Brain tumors - primary

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Radiation Therapy Complications

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

Radiation Therapy for Elderly Patients

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

Temozolomide (Temodar)

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

Investigational Treatments

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

Introduction

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of the meninges.

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

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

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

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

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

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

The brain stem consists of three primary parts:

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

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

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

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

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

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

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

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

Symptoms

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

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

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

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

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

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

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

Memory loss
Impaired concentration
Problems with speech and reasoning
Increased sleep

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

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

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

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

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

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

Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Causes

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

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

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

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

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

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

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

Prognosis

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


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

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

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

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

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

Diagnosis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Common Brain Tumors


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

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


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

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


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

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


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

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



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

Treatment

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

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

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

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

Surgery

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

The standard procedure is called craniotomy.

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

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

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

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

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

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

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

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

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

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

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

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

Radiotherapy

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

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

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

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

Various radiation treatments are now available.

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

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

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

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

Benefits of Stereotaxy. There are numerous benefits for stereotaxy:

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemotherapy

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

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

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

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

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

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

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

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

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

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

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

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

Promising targeted therapies for brain tumors include:

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

Other Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Treatment of Complications

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

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

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

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

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

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

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

Resources

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

References

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

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

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

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

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

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

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

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

A.D.A.M. Copyright

adam.com

Menthol overdose

admin — Thu, 04 Sep 2008 18:59:02 -0700

Overview

Definition
Poisonous Ingredient
Where Found
Symptoms
Home Treatment
Before Calling Emergency
Poison Control, or a local emergency number
What to expect at the emergency room
Expectations (prognosis)

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Menthol is used as a flavoring agent for candy and other products. Menthol poisoning occurs from swallowing pure menthol.

Poisonous Ingredient

Menthol

Where Found

Menthol may be found in:

Candy
Cigarettes
Cold sore medications
Cough drops
Creams and lotions to relieve itching
Gum
Inhalants, lozenges, or ointments to treat nasal congestion
Medications to treat sore mouth, throat, or gums
Mouthwashes
Ointments to treat aches and pains (Ben-Gay, Therapeutic Mineral Ice)
Peppermint oil

Note: This list may not include all uses of menthol.

Symptoms

Bladder and kidneys
- Blood in the urine
- No urine output
Lungs
- Rapid breathing
- Shallow breathing
Gastrointestinal
Heart and blood
- Rapid heartbeat
Nervous system
- Convulsions
- Dizziness
- Unconsciousness

Home Treatment

Seek immediate medical help. If the menthol is in ointment/cream form, wipe away any that remains on the skin's surface. Call Poison Control for further guidance.

Before Calling Emergency

Determine the following information:

The patient's age, weight, and condition
The name of the product (ingredients and strengths, if known)
Time it was swallowed
Amount swallowed

Poison Control, or a local emergency number

The National Poison Control Center (1-800-222-1222) can be called from anywhere in the United States. This national hotline number will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the U.S. use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Take the container with you to the hospital, if possible.

See: Poison control center - emergency number

What to expect at the emergency room

The health care provider will measure and monitor your vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated as appropriate. You may receive:

Activated charcoal
A tube through the mouth into the stomach to wash out the stomach (gastric lavage)
Endoscopy -- camera down the throat to see burns in the esophagus and the stomach
Fluids
Medicines to treat an allergic reaction (diphenhydramine, epinephrine, or prednisone)
Washing of the skin (irrigation), perhaps every few hours for several days

Expectations (prognosis)

How well you do depends on the amount of poison swallowed and how quickly medical treatment is received. The faster you get medical help, the better the chance for recovery.

Swallowing such poisons can have severe effects on many parts of the body.

However, pure menthol is not readily available. The menthol found in many over-the-counter products is usually watered down and mixed with other ingredients. Therefore, how well a patient does also depends on the other ingredients in the product.

Review Date: 2/27/2008

Reviewed By: Stephen C. Acosta, MD, Department of Emergency Medicine, Portland VA Medical Center, Portland, OR. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Source Doc: 1_002673

Carpal tunnel syndrome

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Prognosis
Prevention
Diagnosis
Treatment
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Overview

Several medical conditions can increase the risk for, or even cause, carpal tunnel syndrome (CTS). Diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy are the main conditions associated with CTS. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Most workers who use their hands and wrists repetitively are at risk for CTS. This is especially true if they work in cold temperatures and have medical conditions that make them susceptible to CTS.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role in CTS.

Treatment News:

Several physical therapy techniques have been shown to improve hand strength and function in patients with mild-to-moderate CTS.
Short periods of traction have also been successful in producing long-term relief in patients who have failed other conventional treatments.
Injections of botulinum toxin (Botox) show promise in treating carpal tunnel syndrome.

Risk Factors:

A Swedish study of neurological diseases found CTS to be the second most commonly occurring nerve, nerve root, and nerve plexus disorder among siblings hospitalized with the same condition. Although the study could not distinguish between genetic and environmental causes, clusters of CTS in families may suggest an inherited predisposition.

Introduction

Carpal tunnel syndrome (CTS) is a disorder marked by weakness and pain in the hand and wrist. CTS occurs in the nerves of the hands -- not the muscles, as some people believe. The symptoms of CTS can be incapacitating.

To understand how carpal tunnel syndrome arises, it is important to know the parts of the hand and wrist that are involved.

The Carpal Tunnel. The carpal tunnel is a passageway that forms beneath the strong, broad transverse ligament. This ligament is a bridge that extends across the lower palm and connects the bones of the wrist (carpals), which form an arch below the tunnel.

The Median Nerve and Flexor Tendons. The median nerve and nine flexor tendons pass under the ligament bridge and through the carpal tunnel (similar to a river). They extend from the forearm and up into the hand:

The flexor tendons are fibrous cords that connect to muscles of the fingers (two to each finger) and one to the thumb. They allow flexing of the fingers and clenching of the fist.
The median nerve plays two important roles. It supplies sensation to the thumb, index, middle, and ring fingers, and to the flexor tendons. It provides function for the muscles at the base of the thumb (the thenar muscle).

The median nerve travels through a compartment in the wrist called the carpal tunnel. The ligaments that transverse the nerve are not very flexible. Any swelling within the wrist compartment can put excessive pressure on structures such as the blood vessels and the median nerve. Excessive pressure can constrict blood flow and cause nerve damage. The symptoms from the compression cause pain, loss of sensation, and decreased function in the hand.

It is not completely known how the process leading to carpal tunnel syndrome actually evolves, and how nerve conduction (the passing of the nerve signal) through the wrist becomes changed. In general, carpal tunnel syndrome develops when the tissues around the median nerve swell and press on the nerve. Early in the disorder, the process is reversible. Over time, however, the insulation on the nerves may wear away, and permanent nerve damage may develop.

The following events have been observed in the hands of people with carpal tunnel syndrome:

The protective lining of tendons (called the tenosynovium) swells within the carpal tunnel. Some research suggests that this swelling is caused by build-up of fluid (called synovial fluid) under the lining. Synovial fluid lubricates and protects the tendons.
The transverse ligament, the band of fibrous tissue that forms the roof over the median nerve, becomes thicker and broader.
The swollen tendons and thickened ligament compress the median nerve fibers, just as stepping on a hose slows the flow of water through it. The effect is to reduce blood flow and oxygen supply to the nerve, slowing the transmission of nerve signals through the carpal tunnel. Some cases of carpal tunnel syndrome may be due to enlargement of the median nerve rather than compression by surrounding tissues.

The result is pain, numbness, and tingling in the wrist, hand, and fingers. Only the little finger is unaffected by the median nerve.

Click the icon to see a depiction of carpal tunnel syndrome.

Symptoms

Symptoms of carpal tunnel syndrome usually progress gradually over weeks and months and sometimes years. Anyone with recurrent or persistent pain, numbness and tingling, or weakness of the hand should consult a doctor for a diagnosis. Symptoms often develop as follows:

Initial symptoms include pain in the wrist and hand. Symptoms commonly occur in both hands. (Even when only one hand is painful, the other hand often shows signs of nerve conduction abnormalities on testing.)
Early on, the patient also usually reports numbness, tingling, burning, or some combination on the palm side of the index, middle, and ring fingers. (Typically the fifth finger has no symptoms.) Such sensations may radiate to the forearm or shoulder.
Over time, the hand may become numb, and patients may lose the ability to feel heat and cold. Patients may experience a sense of weakness and a tendency to drop things.
Patients may feel that their hands are swollen even though there is no visible swelling. This symptom may actually prove to be an important indicator of greater severity.

Symptoms may occur not only when the hand is being used but also at night when the patient is at rest. Even in cases where work is suspected as the cause, symptoms typically first occur outside of work. In fact, the disorder may be distinguished from similar conditions by pain occurring at night after going to bed.

Causes

Biologic Causes. Carpal tunnel syndrome (CTS) is considered an inflammatory disorder caused by repetitive stress, physical injury, or medical conditions. It is often very difficult, however, to determine the precise cause of carpal tunnel syndrome. No tests are available to identify a specific cause. Except in patients with certain underlying diseases, the biologic mechanisms leading to carpal tunnel syndrome are unknown. Although an overactive immune response that causes inflammation and damage in the joints or muscles is responsible for a number of arthritic conditions, similar problems are not likely to play an important role in CTS. More likely, reduced blood flow and lack of oxygen are important in the process leading to progressive swelling and scarring.

Working Conditions versus Medical Problems. Although some studies suggest that more than half of CTS cases are associated with workplace factors, there is no strong evidence of a cause and effect relationship. In fact, most studies now strongly suggest that carpal tunnel syndrome is primarily associated with medical or physical conditions such as diabetes, osteoarthritis, hypothyroidism, and rheumatoid arthritis. CTS also tends to occur in people with certain genetic or environmental risk factors such as obesity, smoking, alcohol abuse, or significant mental stress. Of all nerve, nerve root, and nerve plexus disorders, CTS has one of the highest familial risks, implying some type of genetic origin. When such susceptible people are subjected to repetitive hand or wrist work, the risk for CTS can become significant. CTS, then, is very likely to be due to convergences of factors that lead to nerve damage in the hand.

Worker's Compensation and CTS. The issues surrounding workers' compensation are particularly troubling in determining accurately whether labor conditions cause carpal tunnel pain. CTS is a major contributor to workers' compensation cases.

High Force and Vibration. Even though medical and physical conditions may be the initial culprits leading to CTS, certain working conditions are especially related to nerve damage -- if not to pure cases of CTS. Work that involves high force or vibration is particularly hazardous, as is repetitive hand and wrist work in cold temperatures.

In addition to CTS, other disorders of hand and wrist result from these work-related movements. They include the following:

Hand-arm vibration syndrome -- tingling and numbing that persist even after the vibration stops
Cumulative trauma (repetitive stress) disorder
Overuse syndromes
Chronic upper limb pain syndrome

All of these problems are generally associated with repetitive and forceful use of the hands, resulting in damaged muscles and bones of the upper arms.

Psychosocial Factors in the Workplace. Studies indicate that psychosocial factors in the workplace, such as intense deadlines, a poor social work environment, and low levels of job satisfaction, are major contributors to carpal tunnel pain. Such psychosocial conditions are more likely to be important factors in contributing to CTS in office workers, although they also complicate the condition in workers whose work is primarily physical.

A number of medical conditions increase the risk for or even cause CTS. The main conditions associated with CTS are diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Diabetes. CTS is a very common feature of diabetic neuropathy, one of the major complications of diabetes. Neuropathy is decreased or distorted nerve function; it particularly affects sensation. Symptoms include numbness, tingling, weakness, and burning sensations, usually starting in the fingers and toes and moving up to the arms and legs. About 6% of patients with CTS have diabetes. A 2005 study reported that an estimated 85% of patients with type 1 diabetes develop CTS. Development of CTS was related to the patient's age and the length of time they had diabetes. The development of diabetes-related complications, such as kidney disease, is not related to the development of CTS in people with diabetes.

Autoimmune Diseases. In autoimmune diseases, the body's immune system abnormally attacks its own tissue, causing widespread inflammation, which, in many cases, affects the carpal tunnel of the hand. Such autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, and hypothyroidism. Some experts believe that CTS may actually be one of the first symptoms in a number of these diseases. Studies also suggest that CTS patients with these disorders are more likely to have severe CTS that requires surgery.

Diseases that Affect Muscle and Bones. Arthritis, gout, and other medical conditions that damage the muscles, joints, or bones in the hand may cause changes that lead to CTS. In fact, in one 2000 study, susceptibility to muscle and bone diseases was the major risk factor for CTS in British women. Osteoporosis (loss of bone density), although not a direct cause of CTS, increases the risk for wrist fractures that can lead to CTS.

Injuries and Previous Surgeries. Injuries, fractures, and operations that affect the forearm, wrist, or hand may lead to CTS, sometimes many years after the event.

Structural Abnormalities. Inborn abnormalities in the bones of the hand, wrist, or forearm may contribute to CTS.

Chronic Kidney Insufficiency. People who undergo hemodialysis for chronic kidney damage often experience a build-up in the hand of a certain type of protein called beta 2-microglobulin. This build-up can result in CTS. The longer the person has been receiving hemodialysis, the greater the risk of CTS. Certain drugs and procedures (particularly one procedure called hemodiafiltration) are being investigated as having the potential to reduce microglobulin build-up. It is hoped such new methods will delay the need for carpal tunnel surgery in patients undergoing long-term hemodialysis.

Other Diseases. A number of other medical conditions may cause or increase susceptibility to CTS:

Down syndrome
Amyloidosis (a progressive disorder of the connective tissues)
Acromegaly (a disease that leads to abnormally large hands and feet due to excessive growth hormone)
Tumor on the median nerve (removal of the tumor often resolves the CTS in such cases)

Medications. According to case reports, a number of medications may increase the risk for temporary CTS. They include certain medications that affect the immune system (such as interleukin-2), and anticlotting drugs (such as warfarin). There has been conflicting evidence as to whether corticosteroids and hormone replacement therapy may increase risk. More research is warranted before a causal association can be established.

Bone dislocations and fractures can narrow the carpal tunnel, thereby exerting pressure on the median nerve.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role on CTS. Greater body mass appears to reduce nerve flow speed into the hand. Obesity is also related to poor physical fitness, which may also increase risk. A 2005 analysis indicated that weight is strongly linked to the onset of CTS in patients under the age of 63 years, but may be a less important factor as they get older.

Hormonal fluctuations in women play a role in CTS. Such fluctuations may cause fluid retention and other changes in the body that cause swelling. Fluid retention is one reason that CTS may develop during pregnancy.

CTS is strongly associated with a family history of the disorder. Many of these cases can be attributed to physical characteristics or medical conditions associated with CTS, which also run in families. However, in one study, 17% of family clusters of CTS were not associated with any such medical conditions, suggesting the genetic factors may be important in some people. Carpal tunnel syndrome that develops in young people is most likely to have a genetic component.

A 2000 study suggested that some patients with CTS may have a genetic defect that produces higher levels of a certain collagen subtype. Collagen is the protein used to build all connective tissue, muscle, bones, and ligament. The collagen found in CTS patients tends to produce stiffness.

Other genetic factors that may contribute to this disorder include abnormalities in certain genes that regulate myelin, a fatty substance that serves as insulation for nerve fibers.

Risk Factors

Evidence suggests that about 3% of women and 2% of men will be diagnosed with carpal tunnel syndrome during their lifetimes, with peak prevalence in women older than 55. Still, determining how many people actually have CTS is very difficult. Many people report CTS symptoms and have normal test results. Other people have no symptoms and abnormal results. Furthermore, some evidence suggests that, after an apparent a decline in cases, the prevalence of CTS is rising.

A large 2005 study of more than 1,000 patients found that the severity of CTS was mild in 42% of patients, moderate in 18%, and severe in 40%. Patients were an average of about 48 years old. More than five times as many women then men participated in the study.

Older people are at higher risk than younger adults. It is very rare in children.

Many studies indicate that women have a significantly higher risk for carpal tunnel syndrome than men do. According to the National Institutes of Health, women are three times more likely than men to experience carpal tunnel syndrome. The explanation for this greater risk is unknown but may be related to the smaller size of women's carpal tunnel.

Hormonal changes appear to play a major role in CTS.

A 2005 study reported that 17% of pregnant women had CTS. Nearly one-quarter of those had it in both wrists. Early studies have presented conflicting reports regarding when CTS is most likely to occur during pregnancy. One found that most cases occurred in the third trimester, and weight gain increased the risk. Another concluded that CTS developed at any point during the pregnancy. New-onset CTS during pregnancy that is severe and persistent enough to require treatment is uncommon. Most cases go away on their own after delivery. However, in one study, 11% of women reported CTS six months after delivery, and 4.3% of them still had the condition a year afterward.

Breastfeeding has also been linked to flare-ups of inflammatory disorders such as CTS. Breastfeeding temporarily lowers the level of natural steroid hormones.

CTS has also been shown to increase during:

The postpartum period
Menopause

Other conditions that are more specific to women than men may increase their risk for carpal tunnel syndrome:

The hand-intensive nature of housework and typing may contribute to a higher incidence of CTS in women.
Women are also at a much higher risk for autoimmune disorders than men are; such disorders are significantly linked to CTS.

People with close relatives who have carpal tunnel syndrome have a higher risk of developing CTS themselves. This risk may be due to family histories of medical conditions associated with CTS, obesity, or genetic factors.

A number of illnesses, skeletal abnormalities, and injuries can predispose individuals to carpal tunnel syndrome, including autoimmune diseases and arthritic conditions.

At high risk are those whose occupations combine force and repetition of the same motion in the fingers and hand for long periods.

Virtually all workers who use their hands and wrists repetitively are at risk for CTS, particularly if they work in cold temperatures and have factors or medical conditions that make them susceptible.

Computer Users and Typists. Repetitive typing and key entry is highly associated with missing work due to CTS. The risk for CTS in this group, however, is still much lower than with occupations involving heavy labor. Although more than 10% of the computer users complain of CTS symptoms, the evidence implicating computer use as a major cause of CTS is weak. One small 2001 study reported that nerve conduction tests on frequent computer users showed the same rate of CTS (3.5%) as in the general population.

A 2003 study found an association between mouse-use (not keyboard use) and CTS. Typing speed may affect risk in some cases, however. For example, the fingers of typists whose speed is 60 words per minute exert up to 25 tons of pressure each day. In one study, typists with CTS struck the keys with greater force than those without the disorder. A large Danish study showed no increased risk of CTS among people who use computers at work. Another study of workers who used computers heavily (up to 7 hours per day) found no increased risk of CTS among them.

Other Very High-Risk Workers. Workers in the meat and fish packing industries and those who assemble airplanes have the highest risk for CTS, according to one study. Meat packers complained of pain and loss of hand function as long ago as the 1860s. Even today, the incidence of carpal tunnel syndrome in the meat, poultry, and fish packing industries may be as high as 15%. A 2005 study of automobile assembly workers found that the estimated annual rate of CTS ranged from 1 - 10%.

Musicians. Musicians are at very high risk for CTS and other problems related to the muscles and nerves in the hands, upper trunk, and neck. In one study, 20% reported CTS or other nerve disorders in the hands and wrists.

Highest to Lowest Numbers of CTS Events by Job. The following is a list of occupations published by the Bureau of Labor Statistics in 2002 rating workers with highest to lowest total numbers of CTS-related events:

Assemblers
Cashiers
Secretaries
General office clerks
Laborers, non-construction
Bookkeepers, accounting, and auditing clerks
Welders and cutters
Data-entry employees
Textile sewing machine operators
Order clerks
Supervisors and proprietors, sales occupations
Machine operators (unspecified)
Truck drivers
Insurance adjusters, examiners, and investigators
Electrical and electronic equipment assemblers
Packaging and filling machine operators
Janitors and cleaners
Bank tellers
Production inspectors, checkers, and examiners

SOURCES: Bureau of Labor Statistics, U.S. Department of Labor, April 2002

At Home and At Play. People who intensively cook, knit, sew, do needlepoint, play computer games, do carpentry, or extensively use power tools are at increased risk for CTS. Long-distance cycling may make symptoms of carpal tunnel syndrome worse.

Square Wrists. Some (but not all) studies have reported a higher risk for CTS in people with square wrists (the thickness and width are about the same) than in those with the more common rectangular wrists.

Palm Shape. In one study, patients with palms that were both shorter and wider than average, and who also had shorter third fingers, were more likely to have CTS than those without these hand characteristics.

Poor Upper Back Strength. Some researchers claim that poor upper back strength makes people more susceptible to poor posture and injuries in the upper extremities, including carpal tunnel syndrome.

Cigarette smoking slows down blood flow, so that smokers have worse symptoms and slower recovery than nonsmokers do. Increased alcohol intake has been associated with CTS in people with other risk factors.

Poor nutrition, previous injuries, and stress can increase one's risk for carpal tunnel syndrome. In addition, high levels of so-called “bad” cholesterol (low-density lipoprotein, or LDL) have also been linked to an increased risk of CTS.

Prognosis

Carpal tunnel syndrome can range from a minor inconvenience to a disabling condition, depending on its cause and persistence and the individual characteristics of the patient. Many cases of CTS are mild, and when symptoms are of short duration, they often resolve (disappear) on their own. Once a woman with pregnancy-associated CTS gives birth, for instance, the swelling in her wrists and other symptoms almost always subside. Proper treatment of other medical conditions that cause CTS can often help reduce wrist swelling.

In severe untreated cases, however, the thenar muscles at the base of the thumb may whither, and loss of sensation may be permanent. CTS can become so crippling that people can no longer do their jobs or even perform simple tasks at home.

Carpal tunnel syndrome exacts a psychological toll. Anyone who cannot use his or her hands is likely to be depressed and suffer from low self-esteem. People may suffer from daily pain. In severe cases, they may be unable to perform ordinary tasks, such as driving a car or carrying groceries. And equally or even more distressing, they may have to give up enjoyable sports and hobbies.

According to a 2005 report from the Bureau of Labor Statistics, among the major disabling diseases and illnesses, carpal tunnel syndrome was associated with the longest average time away from work (28 days).

Employees with CTS who try to work through the disorder often put more stress on the wrists to compensate for the weakness and pain. The end result is to make the condition worse and impair work performance.

Eventually, the worker with CTS may be forced to give up his or her livelihood. In one study, nearly half of all patients with CTS changed jobs within 30 months of an initial diagnosis. And because of the controversy surrounding the issue of carpal tunnel syndrome and workers compensation, it is not always certain that the worker will receive compensation payments.

Prevention

Because multiple factors may cause carpal tunnel syndrome, there is no single mode of prevention. Treating any underlying medical condition is certainly important. Simple common sense may help minimize some risk factors predisposing a person to work-related CTS or other cumulative trauma disorders. A patient can learn how to adjust the work area, handle tools, or perform tasks in ways that put less stress on the hands and wrists. Proper posture and exercise programs to strengthen the fingers, hands, wrists, forearms, shoulders, and neck may help prevent CTS.

Many companies are now taking action to help prevent repetitive stress injuries. In a major survey, 84% reported that they were modifying equipment, tasks, and processes. Nearly 85% were analyzing their workstations and jobs, and 79% were buying new equipment. It should be stressed, however, that there has been no evidence that any of these methods can provide complete protection against CTS. The optimal corporate approach, if possible, is to reallocate workers suffering from repetitive stress injuries to other jobs.

Altering the way a person performs repetitive activities may help prevent inflammation in the hand and wrist from progressing into carpal tunnel syndrome. For example, replacing old tools with ergonomically designed new ones can be very helpful.

Rest Periods and Avoiding Repetition. Anyone who does repetitive tasks should begin with a short warm-up period, take frequent breaks, and avoid overexertion of the hand and finger muscles whenever possible. Employers should be urged to vary tasks and work content.

A 2001 study conducted by the National Institute for Occupational Safety and Health reported that even taking multiple "microbreaks" (about 3 minutes each) reduces strain and discomfort without decreasing productivity. Such breaks may include the following:

Shaking or stretching the limbs
Leaning back in the chair
Squeezing the shoulder blades together.
Taking deep breaths

Good Posture. Good posture is extremely important in preventing carpal tunnel syndrome, particularly for typists and computer users.

The worker should sit with the spine against the back of the chair with the shoulders relaxed.
The elbows should rest along the sides of the body, with wrists straight.
The feet should be firmly on the floor or on a footrest.
Typing materials should be at eye level so that the neck does not bend over the work.
Keeping the neck flexible and head upright maintains circulation and nerve function to the arms and hands. One method for finding the correct head position is the "pigeon" movement. Keeping the chin level, glide the head slowly and gently forward and backward in small movements, avoiding neck discomfort.

Good Office Furniture. Poorly designed office furniture is a major contributor to bad posture. Chairs should be adjustable for height, with a supportive backrest. Custom-designed chairs, made for people who do not fit in standard chairs, can be expensive. However, the costs are often offset by the savings in medical expenses that follow injuries related to bad posture.

Voice Recognition Software. For CTS patients who must use a computer frequently, a variety of voice recognition software packages (ViaVoice, Voice Xpress, Dragon NaturallySpeaking, IListen) are now available, enabling virtually hands-free computer use.

Keyboard and Mouse Tips. Anyone using a keyboard and mouse has some options that may help protect the hands.

The tension of the keys should be adjusted so they can be depressed without excessive force.
The hands and wrists should remain in a relaxed position to avoid excessive force on the keyboard.
A 2003 study suggested that mouse-use poses a higher risk than keyboard use. Replacing the mouse with a trackball device and the standard keyboard with a jointed-type keyboard are helpful substitutions.
Wrist rests, which fit under most keyboards, can help keep the wrists and fingers in a comfortable position.
Some people recommend keeping the computer mouse as close to the keyboard and the user's body as possible, to reduce shoulder muscle movement.
The mouse should be held lightly, with the wrist and forearm relaxed. New mouse supports (ErgoCat) are also available that relieve stress on the hand and support the wrist.
Some people cut their mouse pads in half to reduce movement.

Innovative keyboard designs may reduce hand stress:

Alternative geometry keyboards (Microsoft Natural Keyboard, Apple Adjustable Keyboard) allow the user to adjust and modify hand positions as well as adjust key tension. Most have a split or "slanted" keyboard that places the wrists at an angle. Studies suggest they are useful in promoting a neutral position for the wrist.
The continuous passive motion (CPM) keyboard lifts and declines gently and automatically every three minutes to break tension on the hands and wrist. A report of a clerical worker with CTS who used this device found an overall improvement of 10 words per minute in the typing tests, a decrease in disability score and symptom severity, and an improvement in function.
A keyless keyboard (orbiTouch) is an innovative device that uses two domes. The typist covers the domes with his or her hands and slides them into different positions that represent letters.

The force placed on the fingers, hands, and wrists by a repetitive task is an important contributor to CTS. To alleviate the effect of force on the wrist, tools and tasks should be designed so that the wrist position is the same as it would be if the arms dangled in a relaxed manner at the sides.

No task should require the wrist to deviate from side to side or to remain flexed or highly extended for long periods.
The handles of hand tools such as screwdrivers, scrapers, paint brushes, and buffers should be designed so that the force of the worker's grip is distributed across the muscle between the base of the thumb and the little finger, not just in the center of the palm.
People who need to hold any tools (including pencils and steering wheels) for long periods of time should grip them as loosely as possible.
In order to apply force appropriately, the ability to feel an object is extremely important. Tools with textured handles are helpful.
If possible, people should avoid working at low temperatures, which reduces sensation in hands and fingers.
Power tools and machines should be designed to minimize vibrations.
Wearing thick gloves, when possible, may lessen the shock transmitted to the hands and wrists. One 2001 study found, however, that wearing gel-padded gloves clearly increased comfort but did not actually protect against compression-induced CTS.

Hand and wrist exercises may help reduce the risk of developing carpal tunnel syndrome. Isometric and stretching exercises can strengthen the muscles in the wrists and hands, as well as the neck and shoulders, improving blood flow to these areas. Performing the simple exercises described below for 4 to 5 minutes every hour may be helpful.

Wrists

Exercise 1.

Make a loose right fist, palm up, and use the left hand to press gently down against the clenched hand.
Resist the force with the closed right hand for 5 seconds. Be sure to keep the wrist straight.
Turn the right fist palm down, and press the knuckles against the left open palm for 5 seconds.
Finally, turn the right palm so the thumb-side of the fist is up, and press down again for 5 seconds.
Repeat with the left hand.

Exercise 2.

Hold one hand straight up shoulder-high with fingers together and palm facing outward. (The position looks like a shoulder-high salute.)
With the other hand, bend the hand being exercised backward with the fingers still held together and hold for 5 seconds.
Spread the fingers and thumb open while the hand is still bent back and hold for 5 seconds.
Repeat five times for each hand.

Exercise 3. (Wrist Circle)

Hold the second and third fingers up, and close the others.
Draw five clockwise circles in the air with the two finger tips.
Draw five more counterclockwise circles.
Repeat with the other hand.

Fingers and Hand

Exercise 1.

Clench the fingers of one hand into a fist tightly.
Release, fanning out the fingers.
Do this five times. Repeat with the other hand.

Exercise 2.

To exercise the thumb, bend it against the palm beneath the little finger, and hold for 5 seconds.
Spread the fingers apart, palm up, and hold for 5 seconds.
Repeat five to 10 times with each hand.

Exercise 3.

Gently pull the thumb out and back and hold for 5 seconds.
Repeat five to 10 times with each hand.

Forearms (stretching these muscles will reduce tension in the wrist)

Place the hands together in front of the chest, fingers pointed upward in a prayer-like position.
Keeping the palms flat together, raise the elbows to stretch the forearm muscles.
Stretch for 10 seconds.
Gently shake the hands limp for a few seconds to loosen them.
Repeat frequently when the hands or arms tire from activity.

Neck and Shoulders

Exercise 1.

Sit upright and place the right hand on top of the left shoulder.
Hold that shoulder down, and slowly tip the head down toward the right.
Keep the face pointed forward, or even turned slightly toward the right.
Hold this stretch gently for 5 seconds.
Repeat on the other side.

Exercise 2.

Stand in a relaxed position with the arms at the side.
Shrug the shoulders up, then squeeze the shoulders back, then stretch the shoulders down, and then press them forward.
The entire exercise should take about 7 seconds.

Diagnosis

Carpal tunnel syndrome (CTS) is most accurately diagnosed using the patients' descriptions of symptoms, and electrodiagnostic tests that measure nerve conduction through the hand. If electrodiagnostic testing is not available, then symptom descriptions and a series of physical tests are useful.

Diagnosing CTS, however, is not straightforward. Only a small fraction of patients exhibit all three factors necessary for a clear diagnosis:

Classic CTS symptoms
Specific physical findings
Abnormal electrodiagnostic test results

Many people have abnormal electrodiagnostic test results without classic symptoms or any symptoms at all. Furthermore, about 15% of the population has symptoms consistent with CTS, but most do not show test results indicating the disorder. In fact, in a 2001 study, some patients who had symptoms, but whose nerve and physical tests were normal, still experienced relief after CTS surgery.

Many cases of CTS are a combination of a medical problem exacerbated by repetitive stress factors at work. The patient should give the doctor a detailed history and description of any complaints, in any part of the body. The patient should report in detail any daily activities that require repetitive hand or wrist actions, abnormal postures, or other regular situations that could affect the nerves in the neck, shoulders, and hands. The patient should report whether the symptoms are more likely to appear at night, or after particular tasks.

Questionnaires. The use of specific questionnaires that score results are quite accurate in assessing the severity of the condition.

Hand Diagram. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate where their symptoms are, including pain, numbness, or tingling, by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

One of the most important first steps in diagnosing CTS is to rule out any underlying medical disorders that may be contributing to the condition. Experts emphasize the need to fully examine patients presenting with symptoms of CTS. Relying only on CTS symptoms, and personal or work histories may result in the failure to detect (and thus properly treat) underlying medical conditions that could be serious. If the doctor suspects that an underlying medical condition may be exacerbating the symptoms, laboratory tests will be performed. The doctor may take an x-ray, for example, to check for arthritis or fractured bones.

Raynaud's Phenomenon. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate the location of their symptoms -- including pain, numbness, or tingling -- by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

Arthritic Conditions. Arthritic conditions, including rheumatoid arthritis, gout, and osteoarthritis, can all cause pain in the hands and fingers that may mimic carpal tunnel disease. The treatment for these conditions, however, is different.

Muscle and Nerve Diseases. Any disease or abnormality that affects the muscles and nerves, including those in the spine, may produce symptoms in the hand that mimic carpal tunnel syndrome.

About 25% of patients with suspected work-related cumulative trauma or repetitive stress disorders have evidence of other conditions that resemble, but are not, carpal tunnel syndrome. A definitive diagnosis is often difficult. Most require treatments similar to those used for CTS: rest, immobilization, steroid injections, and even surgery if conservative management is unsuccessful.


Location	Description
The Median Nerve in Other Locations	Repetitive work can cause pressure on the median nerve in locations other than the wrist and can also affect other nerves in the arm and hand. The branch of the median nerve that runs through the palm of the hand can be damaged directly by repeated pounding or by the use of certain tools requiring a strong grip using the palm, such as needle-nosed pliers. The median nerve can also be pinched in the forearm.
Guyon's Canal Syndrome (Commonly called ulnar tunnel syndrome)	The ulnar nerve can, like the median nerve, can be trapped as a result of repetitive stress. When this nerve is trapped, the condition is sometimes referred to as ulnar tunnel syndrome. It is more correctly known as Guyon's canal syndrome, however, since this is the name of the passage through which the ulnar nerve passes. General symptoms are similar to carpal tunnel syndrome, but patients experience loss of sensation in the ring and little finger and in the outer half of the palm. It can be a separate problem, although it commonly occurs with CTS. In such cases, release surgery for CTS usually also relieves the ulnar nerve entrapment. The ulnar nerve can also be affected at the elbow.
De Quervain's Tenosynovitis	Tenosynovitis is swelling of the slippery covering of the tendons that move the thumb. When it causes pain on the side of the wrist and forearm right below the base of the thumb, it is known as De Quervain's tenosynovitis. (Finklestein's Test may help identify this. Make a fist that encloses the thumb, and bend the wrist sideways and down away from the thumb. If it causes pain, it is likely to be De Quervain's tenosynovitis.) It may be treated with splints or corticosteroid injections. In severe cases release surgery is effective.
Digital Flexor Tenosynovitis (Trigger or Snapping Finger)	Digital flexor tenosynovitis, commonly called trigger or snapping finger, is brought on when a tendon thickens, leaving the finger or thumb in a bent position. This disorder usually occurs when the tendons thicken and form a knot and may arise in those with hypothyroidism, diabetes, gout, rheumatoid arthritis, or connective tissue disorders. It can cause pain and a clicking sound when the trigger finger or thumb is bent and straightened. It can be effectively treated with corticosteroid injections.
Thoracic Outlet Syndrome	Thoracic outlet syndrome is caused by compression of nerves and blood vessels running down the neck into the arm. It can produce symptoms very similar to CTS. Other symptoms may include Raynaud's phenomenon (changes in sensation and temperature in the hand). The compression occurs at the first rib in the front of the shoulder. This may happen after an accident or simply from chronic slouching posture. A doctor may be able to diagnose the condition by detecting diminished blood flow in the arm as the patient raises the affected hand and turns his or her head toward the opposite side. Although the condition is uncommon, a correct diagnosis is important to differentiate it from CTS, since treatments differ. Surgery may be required to relieve pressure on the nerves and blood vessels.

The following findings are helpful in identifying carpal tunnel syndrome:

Less sensitivity to pain where the median nerve runs through to the fingers
Thumb weakness
Inability to tell the difference between one and two sharp points on the fingertips (this is a late sign of carpal tunnel)

Flick Signal. One important and simple test of carpal tunnel is the "flick" signal:

The patient is asked, "What do you do when your symptoms are worse?"
If the patient responds with a motion that resembles shaking a thermometer, then the doctor can strongly suspect carpal tunnel.

Testing for Thumb Weakness. Two questions are useful in determining thumb weakness:

Can the thumb rise up from the plane of the palm?
Can the thumb stretch so that its pad rests on the pad of the little finger pad?

Provocation Tests. Certain tests are conducted to produce symptoms:

Phalen's Test. In Phalen's test, the patient rests the elbows on a table and lets the wrists dangle with fingers pointing down and the backs of the hands pressed together. If symptoms develop within a minute, CTS is indicated. (If the test lasts for more than a minute even patients without CTS may develop symptoms.) This test may be particularly important in determining the severity of CTS and assessing the results of treatment.
Tinel's Sign. In the Tinel's sign test, the doctor taps over the median nerve to produce a tingling or mild shock-sensation.
Pressure Provocation Test. The doctor presses over carpal tunnel for 30 seconds to produce tingling or shock in the median nerve.
Tourniquet Test. This test employs an inflatable cuff that applies pressure over the median nerve to produce tingling or small shocks.
Hand Elevation Test. The patient raises their hand overhead for 2 minutes to produce symptoms of CTS. The test was recently proven to be accurate and may provide useful information when combined with the Tinel's and Phalen's tests.

Electrodiagnostic tests analyze the electric waves of nerves and muscles. These tests can help detect median nerve compression in the carpal tunnel.

Electrodiagnostic tests are the best methods for confirming a diagnosis of CTS at this time. Doctors who perform these tests should be certified by the American Board of Electrodiagnostic Medicine, which uses rigorous standards in qualifying doctors. Specific electrodiagnostic tests, called nerve conduction studies and electromyography, are the most common ones performed:

Nerve Conduction Studies. To perform nerve conduction studies, surface electrodes are first fastened to the hand and wrist. Small electric shocks are then applied to the nerves in the fingers, wrist, and forearm to measure how fast a signal travels through the nerves that control movement and sensation. In suspected cases of CTS, nerve conduction tests can identify over 85% of true carpal tunnel syndrome cases and eliminate 95% of those that are not true CTS. They are less accurate in identifying mild CTS, however. Patients should be sure their practitioners perform tests that compare a number of internal responses -- not just routine testing that records only the responses of muscles located in the palm at the base of the thumb), and those on the second or third fingers.

Nerve conduction tests can also detect causes of symptoms that mimic CTS but should be attributed to other problems, such as pinched nerves in the neck or elbow or thoracic outlet syndrome.

Electromyography. To perform electromyography, a fine, sterile, wire electrode is inserted briefly into a muscle, and the electrical activity is displayed on a viewing screen. Electromyography can be quite painful and is less accurate than nerve conduction. Some experts question, in fact, whether it adds any valuable diagnostic information. They suggest it be limited to unusual cases or when other tests indicate that the condition is aggressive and may increase the risk for rapid, significant injury.
Portable electrodiagnostic testing. Portable electronic devices (such as NC-Stat, Neurosentinel, and the Nervepace digital electroneurometer) are being evaluated for measuring nerve conductivity. They are relatively quick and easy to use on a large scale in an industrial facility. However, the Advancing Association of Neuromuscular and Electrodiagnostic Medicine maintains that these devices are experimental and are not effective substitutes for standard electrodiagnostic studies.

Limitations. Electrodiagnostic studies are not well standardized, and certain conditions can skew the results of either test:

Obesity can slow the speed of electrical conduction.
Anxiety can slow the speed of electrical conduction.
Women and the elderly normally have slower conduction times than younger adult men.
Temperature also affects nerve conduction speed. When undergoing testing, doctors should strictly control room temperature to lessen its impact.

Ruling out other causes is extremely important in order to avoid unnecessary surgery for CTS. Modifications and improvements of these tests are continually being made.

Note: People with abnormal results who have no CTS symptoms are at no higher risk for CTS than those with normal results and no symptoms.

A diagnosis of carpal tunnel syndrome may follow testing the affected hand for numbness, tingling, weakness or pain in specific areas. Muscle and nerve conduction tests may also help affirm or rule out carpal tunnel syndrome.

Ultrasound. Ultrasound imaging, a relatively inexpensive technique that uses sound waves, is showing promise. Studies indicate that it can identify up to 85% of CTS cases, and some suggest it is as effective as electrodiagnostic tests. It may be effective for ruling out other causes of hand pain, such as tendon injuries, tenosynovitis (swelling of the tendon lining), cysts, and blood clots in the median artery (a rare complication that can cause the sudden onset of CTS symptoms). However, results are mixed on its accuracy. Newer color Doppler ultrasound and other technological advances are improving the results achieved with this technique. A 2005 study comparing high-resolution ultrasonography with electromyography found that ultrasonography may be helpful for estimating the symptom severity and problems with nerve conduction.

MRI. Magnetic resonance imaging (MRI), an advanced imaging technique, is being adapted to distinguish weak nerve signals from surrounding tissue, so that eventually it may be able to precisely diagnose CTS. However, studies in 2002 note that it requires special expertise, has limited diagnostic accuracy, and is still too expensive at present for routine use. MRI is accurate in diagnosing carpal tunnel syndrome about 80% of the time, compared to about 85% using electrodiagnostic tests, which remains the preferred method of diagnosis. MRI may be most effective for detecting any internal injuries, tumors, arthritis, or joint damage that might be causing the problem. It may also be valuable in selecting surgical candidates when electrodiagnostic tests produce unusual results or indicate more severe disease than expected. Additionally, an MRI may be useful for evaluating patients if surgery fails to bring relief.

Treatment

It is critical to begin treating early phases of carpal tunnel syndrome before the damage progresses. A conservative approach to CTS, which may include corticosteroid injections and splinting, is the first step in treating this disorder.

Nevertheless, relapse is common, and studies suggest that surgery is a better option for severe CTS. In one study, 89% of patients who had conservative treatments suffered a recurrence of symptoms within a year. Conservative treatments work best in men under 40. They do not work as well in young women. The conservative approach is also most successful in patients with mild carpal tunnel syndrome. Even among these patients, however, one study found that 60% of patients can expect a relapse. Some researchers are reporting better results when specific exercises for carpal tunnel syndrome are added to the program of treatments.

Limiting Movement. If possible, the patient should avoid activities at work or home that may aggravate the syndrome. The affected hand and wrist should be rested for 2 to 6 weeks. This allows the swollen, inflamed tissues to shrink and relieves pressure on the median nerve. If the injury is work related, the worker should ask to see if other jobs are available that will not involve the same actions. Few studies have been conducted on ergonomically designed furniture or equipment, or on frequent rest breaks. However, it is reasonable to ask for these if other work is not available.

Conservative Treatment Approach. In a major analysis, the following conservative approaches were shown to provide symptom relief:

Wrist splints
Corticosteroids (steroids). Injected or short-term oral corticosteroids may be tried if other methods fail.
Yoga. In one study, 8 weeks of regular yoga practice reduced pain significantly more than splinting.
Manual therapy, a type of physical therapy

A major analysis of other conservative approaches found that patients had no significant relief from nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include common pain relievers such as aspirin and ibuprofen (Advil). The same report also found no benefits from diuretics, magnet therapy, laser acupuncture, vitamin B6, exercise, or chiropractic care. Other approaches being investigated include omega-3 fatty acid supplements and cognitive-behavioral therapy.

Underlying Conditions. It is important to treat any underlying medical condition that might be causing carpal tunnel syndrome. For example, reducing inflammation in rheumatoid arthritis or other forms of inflammatory disorders that directly cause CTS is very helpful.

Hypothyroidism and diabetes are diseases that are associated with an increased risk of CTS. The treatments for such diseases may offer some relief for CTS symptoms. For example, insulin helps nerves heal. A study of patients with CTS and type 2 diabetes found that patients who had an initial steroid injection followed by 7 weekly insulin injections had significantly less pain than those who received sham therapy (placebo). More research is needed on the effects of insulin injections in patients with CTS.

Wrist splints are used to keep the wrist from bending. They are not as beneficial as surgery for patients with moderate to severe CTS, but they appear to be helpful in specific patients. In one study, the best success rates were in patients with mild to moderate nighttime symptoms of less than a year's duration. In selected patients, up to 80% reported fewer symptoms, usually within days of wearing the splint.

Although typically the splint is worn at night or during sports, one 2000 study reported that wearing it full time is most beneficial. (In the study, few patients actually complied with the regimen and wore them full time, but any regular use appeared to improve nerve function and symptoms.) The splint is used for several weeks or months, depending on the severity of the problem, and may be combined with hand and finger exercises. A 2005 study reported that a 6-week course of at-night splinting reduced symptom severity in people with CTS and that the benefits were still evident after 1 year.

Corticosteroid Injections. Corticosteroids (also called steroids) reduce inflammation. If restriction of activities and the use of painkillers are unsuccessful, the doctor may inject a corticosteroid into the carpal tunnel. Some experts recommend them for patients with CTS whose symptoms are intermittent, and there is no evidence of a permanent injury. In CTS, steroid injections (such as cortisone or prednisolone) shrink the swollen tissues and relieve pressure on the nerve. Evidence strongly suggests that they offer relief in more than 75% of CTS patients. It should be noted that the pain may increase for a day or two after the injection, and skin color may change.

A study comparing the benefits of two steroid injections (8 weeks apart) to a single injection in the treatment of CTS found the patients did not significantly benefit from the second shot. One injection is therefore enough to achieve the maximum benefit of this treatment.

Unfortunately, in most cases, steroid injections provide only temporary relief, although studies comparing steroid injection to surgery have produced conflicting results. In a major analysis, after 1 month, injections were no more effective than placebo (sham) injections.

However, a recent analysis compared the effects of local steroid injection versus surgery in patients with new CTS of at least 3 months' duration. Over the short term, local steroid injection was better than surgery for relieving symptoms of CTS. And after 1 year, local steroid injection was as effective as surgery. Another study compared steroid injection with open-release surgery and found that the surgery resulted in better outcomes, but not improved grip strength, in patients with CTS over a 20-week period.

Most doctors limit steroid injections to about three per year, since they can cause complications, such as rupture of tendons, nerve irritation, or more widespread side effects such as hypertension or elevated blood sugar levels.

Low-Dose Oral Corticosteroids. Oral corticosteroids are medicines taken by mouth. Short-term (1 to 2 weeks), low-dose use of corticosteroids may provide long-term relief. People with diabetes should not take oral corticosteroids.

Yoga. Some evidence suggests that yoga practice may be specifically very helpful for carpal tunnel, since yoga postures are designed to stretch, strengthen, and balance upper body joints. In one study, people who practiced yoga for 8 weeks experienced significantly reduced symptoms compared to wrist splints or no treatment at all. Two other small studies also reported improvement in pain relief. Positive effects may take a few weeks of regular practice of at least two sessions a week.

General Exercise Program. Some experts have reported that people who are physically fit, including athletes, joggers, and swimmers, have a lower risk for cumulative trauma disorders. Although there is no evidence that exercise can directly improve CTS, a regular exercise regimen using a combination of aerobic and resistance training techniques strengthens the muscles in the shoulders, arms, and back, helps reduce weight, and improves overall health and well-being. In one 2001 study, CTS patients experienced symptom relief and signs of improved nerve conduction after 10 months of participation in an aerobic exercise program (such improvements appeared to be due to both weight loss and higher oxygen levels in the blood). One study found that most people with CTS felt improvement after two months of physical therapy that included exercises to improve balance and posture. People with any chronic medical condition or with risk factors for heart disease should check with their doctors about an appropriate exercise regimen.

If symptoms subside, the patient may proceed with a supervised program of joint mobilization and hand and wrist strengthening and stretching, usually offered by physical or occupational therapists. Hand and wrist exercises may be most beneficial for patients with mild to moderate disease who are also treated with splints and other conservative measures. Graston Instrument-Assisted Soft-Tissue Mobilization (GISTM) and Soft-Tissue Moblization (STM) techniques have been shown to improve nerve conduction, wrist strength, and wrist motion.

Ultrasound employs high-frequency sound waves directed toward the inflamed area. The sound waves are converted into heat in the deep tissues of the hand, which opens the blood vessels and allows oxygen to be delivered to the injured tissue. A major analysis suggested this approach may be effective when used for seven weeks or more.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and ibuprofen (Advil), are the most common pain relievers used for CTS. They block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. Unfortunately, as with most other medications used for carpal tunnel syndrome, there are few well-conducted studies to determine their role in CTS. To date, there is no evidence that they offer any significant relief, and regular use can have serious side effects.

NSAIDs Used. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve joint pain and inflammation. There are dozens of NSAIDs. The following are the most common:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), and ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil), and indomethacin (Indocin).

Regular use of even over-the-counter NSAIDs may be hazardous for anyone. Long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. NSAIDS have been associated with the following side effects:

Ulcers and gastrointestinal bleeding are the major danger with long-term use of NSAIDs.
Increased blood pressure -- most NSAIDs appear to pose this risk, with higher risks observed with piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin). Sulindac has the smallest effect; aspirin has no risk. People with hypertension, severe vascular disease, kidney, or liver problems, and those taking diuretics, must be closely monitored if they need to take NSAIDs.
Delay in emptying of the stomach -- this could interfere with the actions of other drugs. The elderly are at special risk.
Kidney abnormalities -- these have been reported in people taking NSAIDs, which resolve when the drugs are withdrawn. Report any sudden weight gain or swelling to a doctor. Anyone with kidney disease should avoid these drugs.

Other side effects include:

Dizziness
Tinnitus (ringing in the ear)
Headache
Skin rash
Depression
Confusion or bizarre sensation (in some higher-potency NSAIDs, notably indomethacin)
Possible higher risk for miscarriage (particularly if the NSAID is taken for more than a week or around the time of conception)
There is a slight risk for liver abnormalities.

COX-2 Inhibitors (Coxibs). COX-2 inhibitors block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of heart attacks and stroke have prompted the FDA to re-evaluate the risks and benefits of the COX-2s. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. At the time of this update, Celecoxib (Celebrex) was still available, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Ice and Warmth. Ice may provide benefit for acute pain. Some patients have reported that alternating warm and cold soaks have been beneficial. (If hot applications relieve pain, most likely the problem is not caused by CTS but by another condition producing similar symptoms.)

Anesthetic Injections. In some cases, injections of an anesthetic (such as lidocaine) may be helpful. A recent small study compared a painkilling lidocaine patch with a combination lidocaine-steroid injection. The study found the daily use of a 5% lidocaine patch reduced pain as well as the injections. More patients in the patch group reported satisfaction with their treatment. The lidocaine patch is less painful than injections because it is worn on the skin and doesn't require a shot. Doctors noted improvements in 88% of the patients in the patch group, compared with 74% of the patients in the injections group.

Pheresis. The word "pheresis" means to carry. In the case of carpal tunnel, pheresis is a technique being investigated to deliver (to carry) a corticosteroid cream deep within the wrist. One such technique called iontophoresis uses an electrical current, and another called phonophoresis uses ultrasound. One study recently found steroid injections to be superior to iontophoresis and phonophoresis in the treatment of CTS.

Diuretics. Diuretics such as trichlormethiazide reduce fluid in the body. They are sometimes used to treat CTS. However, studies have not reported any significant benefits with these agents.

Low-Level Laser Therapy. Some investigators are working with low-level laser therapy (LLLT), which generates extremely pure light in a single wavelength. The procedure is painless, but studies are mixed on whether it is any more effective than sham treatment. One major analysis reported that laser therapy was more effective over time than steroid injections (although it does not appear to provide much immediate relief.) A 2004 study comparing LLLT with a sham (inactive) therapy reported no significant differences in outcomes between the two groups.

Muscle Stimulation. Two investigative procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and then relax until the process is completed. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including carpal tunnel syndrome.

Traction. Small studies of a hand traction device showed improvement in some patients. The device, called C-TRAC, significantly improved pain, tingling, and numbness in patients who had failed a minimum of 4 months of therapy with conservative treatments such as NSAIDs, night hand splinting, acupuncture, and hand therapy. Patients used the C-TRAC device for 5 minutes three times daily for four weeks, then as needed to maintain long-term improvement.

Many alternative therapies are offered to sufferers of carpal tunnel syndrome and other repetitive stress disorders. Few, however, have any proven benefit. People should carefully educate themselves about how alternative therapies may interact with other medications or impact other medical conditions, and should check with their doctor before trying any of them.

Vitamin B6. Vitamin B6 (pyridoxine) is often used for carpal tunnel syndrome. Studies have not supported its benefits, however, either in oral or cream form. It should also be noted that excessively high doses of vitamin B6 can be toxic and cause nerve damage.

Acupuncture. Acupuncture may be beneficial. New techniques employing painless laser acupuncture may prove to be particularly effective. The National Institutes of Health issued a Consensus Statement on Acupuncture in 1997, which declared this ancient form of treatment useful as a supplement to standard treatment or even as part of a comprehensive management program for CTS.

Chiropractic Therapies. Chiropractic techniques have been useful for some people whose condition is produced by pinched nerves. In one small study, the technique was as effective as medications or wrist splints for relief of pain, though further research is needed.

Magnets. Magnets are a popular but unproven therapy for pain relief. One small study of patients who wore magnets attached to their wrists showed no benefits over those who wore a nonmagnetic placebo (sham) device, although both groups did experience pain relief, perhaps due to a placebo response.

Botulinum toxin type A. Intracarpal injections of botulinum toxin type A (Botox) have been reported to relieve carpal tunnel syndrome in more than half of the small number of patients tested. The product has been safely used to relieve headaches, myofacial pain, and other neuropathic pains.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Several herbal and homeopathic remedies are sold for pain relief. A small 2002 British study suggested that preparations containing arnica, a popular remedy for swelling and bruising, may ease discomfort following surgery for carpal tunnel, but a 2003 study reported no advantages compared to placebo (an inactive substance).

Research indicates that anxiety, depression, and even pain related to CTS can be relieved to some extent with cognitive behavioral therapy. The focus of this therapeutic approach is to change negative thinking about one's ability to manage pain. Cognitive behavioral therapy is particularly helpful in defining and setting limits. It may be expensive and not covered by insurance, although the therapy is usually of short duration, typically six to 20 one-hour sessions, plus homework, which usually includes attempting a task that the patient has avoided because of negative thinking. Even if people cannot afford this type of therapy, support groups for carpal tunnel syndrome and other sufferers of repetitive stress injuries can be very helpful for exchanging information, specific advice, and solace. Stress management techniques can also be useful in dealing with the psychological and emotional issues accompanying these injuries.

Surgery

Every year more than 200,000 people in the US undergo surgeries for carpal tunnel syndrome. Surgery for CTS is among the most common hand surgeries. In various trials, 70 - 90% of patients who underwent surgery were free of nighttime pain afterward.

Although evidence strongly suggests that surgery is more effective than conservative approaches (at least in patients with moderate to severe CTS), the decision about whether to have surgery to correct CTS, and when to have it, is a troubling one for patients. Electrodiagnostic and other tests used to confirm the presence of CTS are not very useful in determining the best candidates for surgery. For example, results suggesting severe CTS may not relate at all to surgical success or the lack of it.

In general, patients with the following characteristics are less likely to respond to conservative treatment and, therefore, might benefit from surgery:

Older than 50 years of age
Symptoms lasting 10 months or longer
Continual numbness
Muscles in the base of the palm have begun to shrink
Symptoms occur within 30 seconds during a Phalen's test

According to a 2002 study, if none of these factors are present, conservative therapies (splinting and anti-inflammatory agents) are effective in two thirds of patients. However, the conservative approach was ineffective in 60% of patients if only one of these factors were present, in 83% with only two of them, and in virtually all patients who had three or more.

Surgery does not cure all patients, and because it permanently cuts the carpal ligament, some wrist strength is often lost. A number of experts believe that release surgery is performed too often. They recommend aggressive conservative treatment (such as splints, anti-inflammatory agents, and physical therapy) before choosing the more invasive option (surgery). Nevertheless, other experts argue that CTS is often progressive and will worsen over time without surgery. Furthermore, evidence now shows that surgery is better than splints and conservative measures for the relief of pain. Factors that may increase the chances for successful surgery:

Having surgery performed within 3 years of the diagnosis of the disorder
Being in good general health
Having very slow nerve conduction results, but also having some muscle strength before surgery
Symptoms are worse at night than during the day

Factors that may reduce the chances for success:

Being elderly may affect the chances of successful surgery. However, a study found that the majority of patients over age 65 who had surgery were either completely or very satisfied.
Having very severe symptoms before surgery may reduce the chance for successful surgery.
Performing heavy manual labor, particularly working with vibrating tools, may lead to a less successful surgery. Medical evidence has found that only slightly more than half the people who used vibrating hand-held tools were symptom-free 3 years after a CTS operation.
Having very poor nerve conduction results before surgery may reduce the chance for successful surgery. However, some patients with severe symptoms who have normal neurological and physical test results, could still experience significant relief from CTS surgeries.
Patients who are on hemodialysis have good initial success, but approximately half deteriorate in about a year and a half.
Alcohol abuse can negatively affect the results of CTS surgery.
Poor mental health can lead to less successful surgery.
Patients with diabetes and high blood pressure may be more likely to require a second operation.

Factors that make no difference in results:

Patients whose CTS is due to nerve damage from medical conditions, such as diabetes, rheumatoid arthritis, or hypothyroidism. Such patients appear to have the same outcome as those without such conditions, and such disorders should not preclude them from surgery.

Open Release Surgery. Traditionally, surgery for CTS entails an open surgical procedure performed in an outpatient facility. In this procedure, the carpal ligament is cut free (released) from the median nerve. The pressure on the median nerve is therefore relieved. The surgery is straightforward.

In treating carpal tunnel syndrome, surgery may be required to release the compressed median nerve. The open release procedure involves simply cutting the transverse carpal ligament.

The Mini-Open Approach. In recent years, more surgeons have adopted a "mini" open -- also called short-incision -- procedure. This surgery requires only a one-inch incision, but it still allows a direct view of the area (unlike endoscopy, which is viewed on a monitor). The mini-open approach may allow for quicker recovery while avoiding some of the complications of endoscopy, although few studies have investigated its benefits and risks. In a 2005 report, the mini-open approach was directly compared with open release surgery. The recovery time in patients receiving the mini-open approach was shorter than with the open approach, and results were about the same 30 months after the surgery.

Endoscopy. Endoscopy for carpal tunnel syndrome is a less invasive procedure than standard open release.

A surgeon makes one or two 1/2-inch incisions in the wrist and palm, and inserts one or two endoscopes (pencil-thin tubes).
The surgeon then inserts a tiny camera and a knife through the lighted tubes.
While observing the underside of the carpal ligament on a screen, the surgeon cuts the ligament to free the compressed median nerve.

Patients report less pain than those who had the open release procedure, and return to normal activities in about half the time. Nevertheless, at this time the best evidence available does not show any significant long-term advantages of endoscopy over open release in terms of muscle or grip strength or dexterity. The endoscopic approach may even carry a slightly higher risk of pain afterward. This may be due to a more limited view of the hand with endoscopy. (In the open release procedure, the surgeon has a full view of the structures in the hand.) One report indicated a nearly 3-fold increased risk of reversible nerve injury with endoscopic carpal tunnel release, compared with open carpal tunnel release. On the other hand, a recently published review of 486 patients, who had a total of 753 endoscopic release procedures, showed an extremely low number of complications following the procedure. This study calls into the question the widely held belief that endoscopy carries a higher risk of complications. The study also noted that 90% of the patients returned to their original line of work.

Timing for Recovery. Patients should expect the following course:

For some patients, release surgery relieves CTS symptoms of numbness and tingling immediately.

People who have the operation on both hands are completely incapacitated for about two weeks and must have someone to help them at home.
Returning to strenuous work right after surgery may cause the symptoms to return. Patients generally stay out of work for at least a month and often much longer, depending upon the type of surgery and severity of the condition. Recovery time appears to be faster with endoscopy than with open release.
Immediately after surgery patients usually experience a decline in grip strength and dexterity. Studies have reported a wide range of recovery in this area. In one study, grip and pinch strengths reached better levels than before surgery within 6 weeks. In another study, however, grip strength and dexterity did not return to before-surgery levels until 25 weeks after open surgery. The scar may remain tender for up to a year.
Peak improvement (the best level of improvement a patient can reach) may take a long time; in one study, it took an average of almost 10 months.

Physical Therapy. Physical therapy is very important to help rebuild wrist strength. While physical therapy does not reduce the recurrence (return) of symptoms or improve the long-term benefits of surgery, it does accelerate recovery after surgery. Hand exercises can help restore circulation, muscle strength, and joint flexibility in the hand and wrist. Wearing a splint to immobilize the wrist after surgery has no benefits.

Treatment failure and complication rates of CTS surgery vary.

Complications after surgery may include the following:

Nerve damage with tingling and numbness (usually temporary)
Infection
Scarring
Pain
Stiffness. Loss of some wrist strength is a complication that affects between 10% and a third of patients. Endoscopy may have better results than open release. Some patients who have jobs requiring significant strength of the hand and wrist may not be able to perform them after surgery. Such workers may also have problems in other parts of the upper body, including elbows and shoulders. These problems do not go away with surgery and can persist. Studies indicate that between 10 - 15% of patients change jobs after a CTS operation.

If pain and symptoms return, the release procedure may be repeated.

Reasons for procedure failure include:

Incomplete release of the ligament
Extensive scarring
Recurrence of the disorder due to underlying medical conditions

Patients who had open release surgery appear more likely to require repeat operations compared with those who have had endoscopic surgery.

Neurolysis. In severe cases or when scarring is extensive after surgery, surgeons may choose to sever the nerves that are responsible for the pain, using a procedure called external or internal neurolysis. The procedure may extend recovery time substantially, and the need for repeat surgeries may be higher in those who undergo the procedure. One report indicated that neurolysis should be considered if there has not been any recovery within 3 months after surgery, after which improvement is unlikely. It is unclear if this approach offers any benefits over conservative measures to free the nerve from surrounding scar tissue.

Implants. In another procedure for recurrent carpal tunnel syndrome, doctors may take muscle flaps or even fatty tissue from other parts of the body and implant them at the site of the nerve injury. Such flaps enhance the development of new blood vessels, provide padding, and possibly serve as a bed for nerve regrowth. These implants may be used with or without cutting the nerve. Another procedure called vein wrapping uses grafts taken from veins to help protect the scarred nerves.

Resources

www.aanem.org -- Advancing Association of Neuromuscular and Electrodiagnostic Medicine
www.apta.org -- American Physical Therapy Association
www.aoec.org -- The Association of Occupational and Environmental Clinics
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.assh.org -- American Society for Surgery of the Hand
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- Association for the Study of Pain
www.aan.com -- American Academy of Neurology
www.nih.gov/niams -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nlm.nih.gov/medlineplus/carpaltunnelsyndrome.html -- Information on CTS
www.cdc.gov/niosh/homepage.html -- National Institute for Occupational Safety and Health
www.workerscompensationinsurance.com -- Resources for injured workers
www.keybowl.com -- orbiTouch keyboard
www.ergodevices.com -- Hand and wrist support keyboard

References

Tsai CP, Liu CY, Lin KP, Wang KC. Efficacy of botulinum toxin type a in the relief of carpal tunnel syndrome: A preliminary experience. Clin Drug Investig.2006;26:511-515.

Burke J, Buchberger DJ, Carey-Loughmani MT, et al. A pilot study comparing two manual therapy interventions for carpal tunnel syndrome. J Manipulative Physiol Ther.2007;30:50-61.

Hemminki K, Li X, Sundquist K. Familial risks for nerve, nerve root and plexus disorders in siblings based on hospitalizations in Sweden. J Epidemiol Community Health. 2007;61:80-84.

Porrata H, Porrata A, Sosner J. New carpal ligament traction device for the treatment of carpal tunnel syndrome unreposnive to conservative therapy. J Hand Ther. 2007;20:20-28.

Review Date:
3/14/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Kidney stones

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Diagnosis
Treatment
Medications
Other Treatments
Complications
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research:

Patients who have the most common type of gastric bypass surgery, the Roux-en-Y, are at increased risk for kidney stones, beginning 6 months after surgery, according to a study published in 2006.

Causes of Kidney Stones:

Calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of this imbalance is unknown.
Having acidic urine or too much uric acid in the body leads to the formation of uric acid stones.
Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes.
Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Treatments:

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 - 3 days.
Certain medications can prevent recurrence of stones in people who are at high risk.
Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. The shock waves are delivered from outside the body.
Surgery may be necessary if the stone or stones are too big to pass, and cannot be broken down through ESWL.
A change of diet and increased drinking of fluids, especially water, will help prevent a recurrence.

Introduction

Kidney stones are hard, solid rocks that form in the urinary tract. In many cases, the stones are very small and can pass out of the body without any problems. However, if a stone (even a small one) blocks the flow of urine, excruciating pain may result, and prompt medical treatment may be needed.

The process of urination begins in the kidneys. The kidneys filter out fluids and waste from the body, producing urine. The two kidneys are located deep behind the abdominal organs, below the ribs and toward the middle of the back.

Each kidney contains over a million nephrons. These are the tiny filtration units of the kidney.
Each nephron is composed of a tiny group of blood vessels (a glomerulus) enclosed in a funnel-like structure called Bowman's capsule.
Each glomerulus filters waste products, water, and salts out of the liquid part of the blood (plasma) that has entered the kidney.
About 1% of the plasma is converted into urine. The rest returns into the blood to prevent dehydration. Urine is primarily made of acids, urea, and creatinine (nitrogen compounds).
Urine passes from Bowman's capsule into tiny tubules, which lead to large collecting tubes in the center of the kidney. As the urine passes through this network, it becomes more concentrated.
Urine then flows from the kidney through thin tubes called ureters into the bladder.
The bladder's stretchy walls expand to store the incoming urine until it leaves the body through a tube called the urethra.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Click the icon to see an image of the urinary tract.

Occasionally, various salts build up on the inside surfaces of the kidney and form crystals. Eventually these crystals become large enough to form stones in the kidney, a condition called nephrolithiasis. Kidney stones (renal calculi) may also form in the ureter or the bladder. Combinations of minerals and other chemicals, some derived from a person's diet, make up the salts in these stones.

Click the icon to see an image of the kidney stones.

Calcium Stones. About 70 - 90% of all kidney stones are made of calcium, usually combined with oxalate, or oxalic acid. A number of common vegetables, fruits, and grains contain oxalate.

About 6% of calcium stones are made of calcium phosphate (called brushite).

Uric Acid Stones. Uric acid is responsible for close to 10% of kidney stones. It is the breakdown product of purines, nitrogen compounds found in our bodies and in certain foods. The breakdown of purines to uric acid occurs in the liver, and from there uric acid enters the bloodstream, most of it passing into the kidneys. From the kidneys, uric acid leaves the body in the urine. Often, uric acid stones occur with calcium stones.

Struvite Stones. Struvite stones are made of magnesium ammonium phosphate. They are almost always associated with certain urinary tract infections. Worldwide, they make up to 30% of all kidney stones. In the United States, however, less than 15% of all stones are struvite. Most struvite stones occur in women. The rate of these stones may be declining in America, perhaps because of better control of urinary tract infections.

Cystine Stones. A build-up of the amino acid cystine, a building block of protein, causes 1% of kidney stones in adults and up to 8% of stones in children. The tendency to form these stones is inherited. Cystine stones are marked by rapid growth and recurrence, which, if not treated promptly, can eventually lead to kidney failure.

Xanthine Stones. Other kidney stones are composed of xanthine, a nitrogen compound. These stones are extremely uncommon and usually occur as a result of a rare genetic disorder.

Click the icon to see an animation about kidney stones.

Causes

The key process in the development of kidney stones is supersaturation.

The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

Magnesium
Citrate
Pyrophosphate
Enzymes

These substances:

Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
Prevent crystal formation
Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

Uric acid and cystine stones mainly form in acidic urine.
Calcium phosphate and struvite stones increase in alkaline urine.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known, and the condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones:

Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
Renal calcium leak: In this condition, the filtering processes in the kidney fail, causing an increase of calcium in the urine.
Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

Severe vitamin B6 deficiencies (usually due to genetic disorders)
Deficiencies in Oxalobacter formigene, an intestinal bacteria that breaks down oxalate
Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes a buildup of oxalate
Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

A study published in 2006 found that patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, were at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. The study found that patients who underwent the procedure developed hyperoxaluria, and the condition was common 12 months after surgery. The authors also noted an increased number of kidney stone incidents in this patient group.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
Immobilization: Lack of movement can lead to kidney stones.
Renal tubular acidosis: This disorder causes acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream but also reduces protective citrate levels.

Hyperuricosuria is a condition of high levels of uric acid in urine. It occurs in between 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine (hypocitraturia) is a significant risk factor for calcium stones. In addition, hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

Renal tubular acidosis
Potassium or magnesium deficiency
Urinary tract infection
Kidney failure
Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Human body tissues, certain foods, and certain alcoholic drinks contain substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal.

The following conditions are usually seen in patients with uric acid stones:

Too much acid in the urine for a long period (the most important cause of uric acid stones)
Lower than normal amounts of urine produced.
Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
Diabetes: New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings were published in the May 2006 Journal of the American Society of Nephrology.
Insulin resistance: People with insulin resistance are at an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
Genetic factors: Genetic factors can increase a person's risk for uric acid stones.
Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

Certain medications (chemotherapy drugs, diuretics, and salicylates)
Binge drinking
Not eating for long periods of time (fasting)
Lead poisoning
Blood cancers (leukemia, multiple myeloma, and lymphomas)
Some rare types of anemia (low levels of red blood cells in the blood)
Chronic diarrhea

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.

Risk Factors

Kidney stones are one of the most common disorders of the urinary tract. They are an ancient health problem. Evidence of kidney stones has been found in an Egyptian mummy estimated to be more than 7,000 years old.

An estimated 1.3 million Americans seek medical help for kidney stones each year. At this time, studies suggest kidney stones affect over 5% of Americans and that the rate has increased since the 1970s, perhaps because of increases in animal and dietary protein intake.

Men. The risk of kidney stones increases in a man's 40s and continues to rise until age 70. Caucasian men are at higher risk than other groups.

Women. The risk of kidney stones peaks in a woman's 50s. In younger women, stones are more likely to develop during the late stages of pregnancy. Pregnant women tend to have a higher calcium intake, but their kidneys do no handle the calcium as well as they did prior to pregnancy. Kidney stones are still a rare occurrence during pregnancy, however, affecting only 1 in 1,500 pregnancies.

Risk Factors in Children. Stones in the urinary tract in children are usually due to genetic factors. Most of the time, the cause is too much calcium in the urine (hypercalciuria). Deformities in the urinary tract pose a significant risk for kidney stones in children. Children with low birth weight who need to be fed intravenously are also at risk for stones.

Obesity and weight gain are both associated with an increased risk of kidney stones.

Men who weigh more than 220 lbs are 44% more likely to develop kidney stones than men who weigh less than 150 lbs.
Women who are obese are 90% more likely to develop kidney stones than women with a lower body mass index (BMI).

Higher BMIs and larger waist circumferences are both risk factors for kidney stones. Researchers think that there may be a link between fat tissue, insulin resistance, and urine composition. People with larger body sizes may excrete more calcium and uric acid, which increase the risk of kidney stone formation.

A family history of kidney stones increases one's risk for the condition. Researchers are looking into markers or other factors that might predict kidney stones in relatives, although none has yet been clearly identified. One report found that among the siblings of patients with calcium stones, sisters with higher urinary calcium levels and more acidic urine were more likely to develop stones. Brothers with high urinary calcium, low urinary potassium, and older age were more likely to have the problem. A family history of gout may also make a person vulnerable to stones.

According to a 2003 study of American ethnic groups, Caucasians have the highest incidence of kidney stones (5.9%) followed by Mexican Americans (2.6%). African-Americans have the lowest risk (1.7%).

Dietary factors, minerals in local water, or both may contribute to geographic differences that have been observed in the occurrence of kidney stones. Studies have reported the highest occurrence of kidney stones in the southern region of the United States and the lowest in the west. One study suggested that the higher risk may be due to a higher rate of high blood pressure in the southern states and certain dietary habits, particularly lower intake of magnesium and low use of calcium supplements.

Specific Foods. In general, certain foods increase the risk for stones only in people who have genetic or medical vulnerability. People whose diets are high in animal protein and low in fiber and fluids may be at higher risk for stones. A number of foods contain oxalic acid, but there is no proof that such foods make any major contribution to calcium oxalate stones in people without other risk factors. However, several studies have shown that increasing dietary calcium and restricting salt, animal protein, and foods rich in oxalate can help prevent calcium oxalate stones from returning.

Stress. One study reported that people who had a major, stressful life experience were more likely to develop stones than those who had not. Some experts speculate that this increased risk may be due to a hormone called vasopressin, which is released in response to stress. Vasopressin also increases the concentration of urine.

Sleep Position. Sleeping in the same position consistently may influence risk. A 2001 study reported that in people who had a history of kidney stones, recurrences tended to occur on the same side that people slept on. An earlier study suggested that people who had kidney stones were more apt to sleep on their stomachs. Movement during sleep did not appear to affect the risk.

Being Bedridden. Any medical or physical condition that keeps a person in bed or immobile increases blood levels of calcium from bone breakdown, thereby posing a risk for stone formation.

Gout. Patients with gout are at a high risk of uric acid stones. These patients have very acidic urine, and a 2002 study suggested that the two disorders may have a common source.

High Blood Pressure. Persons with high blood pressure are up to three times more likely to develop kidney stones. It is not entirely clear whether having high blood pressure increases the risk for a stone, whether stones lead to high blood pressure, or if there is an action linking both.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis cause problems in absorption of substances in the intestines. These problems significantly increase the risk for kidney stones, particularly in men.

Urinary Tract Infections (UTIs): Urinary tract infections are almost always the cause of struvite stones.

Hyperparathyroidism: The parathyroid glands regulate calcium levels in the body through the parathyroid hormone. In hyperparathyroidism, one or more of these glands makes too much parathyroid hormone. Some people with hyperparathyroidism develop kidney stones. Surgery to remove the hyperactive parathyroid gland in such patients reduces the risk for stone formation, but the risk still remains high for some time after surgery.

Other Medical Conditions. Kidney disease, chronic diarrhea, certain cancers (such as leukemia and lymphoma), and sarcoidosis put people at higher risk for stones.

AIDS medications. Over 10% of persons with AIDS who take the medicine indinavir develop stones. The risk is even higher in patients with AIDS who also have hepatitis B, hepatitis C, or hemophilia, as well as those who are very thin or who take the antibiotic combination TMP-SMX. In one study of persons with AIDS who took a combination of indinavir, zidovudine, and lamivudine, 36% developed kidney stones.

Other Drugs. Kidney stones are a rare side effect of thyroid hormones and loop diuretics (drugs that increase urination). In fact, diuretics are also used to prevent calcium stones. Certain cancer chemotherapies can also cause kidney stones. Long-term use of medications, such as antacids, which change the acidic content of urine, may increase the risk for kidney stones.

Symptoms

In many cases, kidney stones do not produce symptoms. However, if a stone becomes stuck in the ureter (the thin tube between the bladder and the kidney), symptoms can be very severe. Often, they vary depending on the stone's location and its progress.

Kidney stone attacks tend to be most common late at night or in the early morning, possibly because of minimal urine output or constriction of the ureters during the early morning hours. Kidney stone attacks are least common during the late afternoon

Pain usually begins abruptly on one side and then usually continues as intense, constant pain. (In some cases it persists for a few minutes, disappears, and then returns after about 10 minutes.)
The patient cannot become comfortable and usually stands, sits, paces, or reclines in a vain search for a position that will bring relief.
If the stone is in the kidney or upper urinary tract, the pain usually starts in one flank area (to the side of the back near the waist). It typically moves to the groin as the stone passes down.
If the stone is too large to pass easily, the pain follows the muscle contractions in the wall of the ureter as they try to squeeze the stone along into the bladder.
Nausea and vomiting may occur.
Blood in the urine may be present.
As the stone passes down the ureter closer to the bladder, a person may feel the need to urinate more often or a burning sensation during urination.
If fever and chills accompany any of these symptoms, an infection may be present.

The size of the stone does not necessarily predict the severity of the pain; a very tiny crystal with sharp edges can cause intense pain while a larger round stone may not be as distressing. Struvite stones can often occur without symptoms.

Diagnosis

The doctor will perform a physical exam. This includes pressing against abdominal areas for tender locations that might indicate the presence of the stone.

The patient's age is a significant factor. Kidney stones that occur in children and young patients are more apt to result from inherited problems that cause cystine, xanthine, or, in some cases, calcium oxalate stones. In adult patients, calcium stones are most common.

A medical history may help predict which crystal has formed the stone. The doctor will need to know the following:

Any previous kidney stone attacks
Histories of cancer, sarcoidosis, or small bowel disease
Any medications being taken, including non-prescription substances, particularly high doses of vitamins D or C and calcium-containing antacids

Many conditions can cause symptoms similar to kidney stones. Usually the diagnosis is easily made because of the specific nature of the symptoms, but it is not always clear. Urinary tract infections can cause similar, but usually less intense, pain. In fact, infection may be present with a kidney stone. Other causes of pain that may mimic kidney stones include:

Gallstones
Diverticulitis (infection or irritation of abnormal pockets in the intestines)
Intestinal blockage
Blood clots
Irritable bowel syndrome
Appendicitis
Stomach ulcers
Hiatal hernia (when the upper part of the stomach bulges into the chest, through an opening in the diaphragm)
Pancreatitis (inflammation of the pancreas)
Hepatitis
Pelvic inflammatory disease
Inflammatory bowel disease (Crohn's and colitis)
Heart attack

Various imaging techniques are helpful in determining the presence of kidney stones. The best approach uses spiral (or helical) computed tomography scans. If it is not available, the patient will need ultrasound or standard x-rays. If no stones show up, but the patient has severe pain that suggests the presence of kidney stones, the next step is an intravenous pyelogram.

X-Rays. A standard x-ray of the kidneys, ureters, and bladder may be a good first step for identifying many stones, since many are visible on x-rays. Calcium stones can be identified on x-rays by their white color. Cystine crystals can also show up on x-rays.

Spiral (or Helical) Computed Tomography. A type of computed tomography (CT) scan, called a spiral or helical CT scan, is currently the best method for diagnosing stones in either the kidneys or the ureters. This test is fast, does not require instruments or foreign chemicals to enter the body, and provides detailed accurate images of even very small stones. If stones are not present, a spiral CT scan can often identify other causes of pain in the kidney area. It is better than x-rays, ultrasound, and intravenous pyelogram -- the previous standard test for detecting kidney stones. Experts hope spiral CT will eventually be able to identify the chemicals present in a stone.

Ultrasound. Ultrasound can detect clear uric acid stones and obstruction in the urinary tract. It is not useful for finding very small stones, but some research indicates that it may be a useful first diagnostic step in the emergency room to help predict the likelihood of a stone, including suspected stones in children.

Intravenous Pyelogram. With intravenous pyelogram (IVP), the doctor injects a special dye into the patient. A technician will then take x-rays as the dye enters the kidneys and travels down the urinary tract. IVP is invasive but, until recently, was the most cost-effective method for detecting stones. Where it is available, spiral CT is now preferred, since it gives a faster diagnosis, is more accurate, is safer, and is similar in cost.

In any case, IVP should not be used on patients with kidney failure. There is also a risk for an allergic reaction to standard dyes, although newer less allergenic ones are becoming available.

In the procedure intravenous pyelogram (IVP), the patient is injected with dye. X-rays are taken as the dye travels through the urinary tract. This procedure is done to confirm the presence of kidney stones, although some stones may be too small to see.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) techniques are showing promise for diagnosing urinary tract obstruction but do not yet accurately reveal small stones, or ones that do not cause a blockage. Because no radiation is involved with MRI, however, it may prove to be a good option for pregnant women.

Urine samples are required to evaluate features of the urine, including its acidity and the presence of:

Red or white blood cells
Infection
Crystals
High or low levels of chemicals that inhibit or promote stone formation

Clean-Catch Urine Sample for Culturing. After determining that a kidney stone is present, the health care provider usually gives the patient a collection kit, including filters, to try to catch the stone or gravel as it passes out. The urine may also be tested (cultured) for the presence of infection-causing organisms. A clean-catch urine sample is almost always required for culturing. To provide a clean catch, do the following:

First, wash your hands thoroughly, then wash the penis or vulva and surrounding area four times with downward strokes, using a new soapy sponge each time.
Begin urinating into the toilet and stop after a few drops.
Position the container to catch the middle portion of the urine stream. Ideally, this urine will contain only the bacteria and other evidence of the stone.
Urinate the remainder into the toilet.
Tighten the cap on the container securely, being careful not to touch the inside of the rim.

Click the icon to see an image of a calcium urine test.

Twenty-Four Hour Urine Collection. A 24-hour urine collection may be needed to measure urine volume and levels of acidity, calcium, sodium, uric acid, oxalate, citrate, and creatinine.

You should not change any of your usual eating or drinking patterns when performing this test.
Discard the first urination on the day of the test.
Afterward all urine passed over the next 24 hours is collected, including the first urination on the morning of day two.
A second 24-hour urine collection may be needed to determine if treatment is working or if the first analysis was not conclusive and the doctor suspects a less common stone, such as a cystine or xanthine stone.

Click the icon to see an image of a uric acid urine test.

Urine tests that are used to determine the specific chemical and biological factors causing the stone should be performed about 6 weeks after the attack, since the attack itself may change the levels of such substances, including calcium, phosphate, and citrate. It should be noted that calcium levels in the urine may be abnormal even in many people without stones. In addition, high urinary concentrations of calcium may pose a greater or lesser risk depending on age. (In one 2001 study, middle-aged adults with high urinary calcium concentrations had a much greater risk than older adults with high levels.)

The kidney stones obtained from the urine sample are examined under a microscope. The crystal formations are often specific enough so that the doctor is able to identify the substance causing the stone.

Calcium oxalate crystals are eight-sided, while calcium phosphate crystals tend to have irregular shapes.
Uric acid stones are sometimes described as pear-shaped or diamond-shaped.
Some struvite stones have very specific shapes commonly described as "coffin lids." Struvite crystals may also occur in a formation known as a staghorn, which can be large and damaging to the kidney.

Testing whether urine is acidic or alkaline helps to identify the specific type of stone. The levels of acidity or alkalinity in any solution, including urine, are indicated by the pH scale:

A pH value of 7.0 is neutral.
A solution with a low pH (below 7.0) is acidic. (A low pH favors uric acid and cystine stones.)
A solution with a high pH is alkaline. (A high pH favors calcium phosphate and struvite stones.)

A dipstick test for blood in the urine (called hematuria) is typically performed when patients appear in the emergency room with flank pain (the primary symptom of kidney stones). About a third of kidney stone patients, however, do not show blood in the urine, so other tests may be needed.

Blood Tests for Stone Factors. Blood and urine tests help determine what substances form the crystals. This allows the doctor to determine the appropriate treatment and preventive measures.

Blood tests may help determine blood levels of urea nitrogen, creatinine, calcium, phosphate, and uric acid for patients with known or suspected calcium oxalate stones. Doctors will usually schedule these tests about 6 weeks after the attack, in order to measure these substances when the stone has been passed, and the patient has been stabilized. This is particularly true in patients with recurrent stones.

Parathyroid Tests. Tests to detect parathyroid hormone levels are given if the doctor suspects hyperparathyroidism, based on other signs and symptoms.

Tests for Infection. A test result that shows a high white blood cell count might indicate infection. Such results, however, could be misleading, since the number of white blood cells could also increase in response to the extreme physical stress of a kidney stone attack.

Tests for Metabolic Problems. About half of children with stones have an identifiable metabolic disorder, which increases their risk of stone recurrence five-fold. Experts argue whether tests for metabolic disorders are routinely needed once the stone composition has been determined. Studies suggest the following:

People with recurrent calcium stones have a wide range of irregular blood or urine test results, indicating a variety of possible metabolic disorders. For example, calcium stones in middle-aged women may be due to parathyroid abnormalities.
Calcium phosphate stones most likely result from renal tubular acidosis.
People with non-calcium stones generally have identifiable metabolic disorders.
Determining the stone composition may be sufficient for treatment, and may help avoid unnecessary metabolic tests.

Treatment

When tests show there is a kidney stone, the next step is to determine treatment. The patient should be admitted to the emergency room if they have severe vomiting, fever, or symptoms of infection.

Strong opioid painkillers, such as meperidine (Demerol), are often required for a severe kidney stone attack. However, doctors will usually not give such drugs until they confirm the presence of a kidney stone on an x-ray. In some cases, powerful nonsteroidal anti-inflammatory drugs (NSAIDs) may work just as well as opioids, and they have fewer side effects. However, they do take longer to work.

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 to 3 days. In some cases, a stone may take weeks to months to pass, although pain usually goes away before that.

The patient should drink plenty of water (two to three quarts a day) to help move the stone along, and take painkillers as needed. The doctor usually provides a collection kit with a filter and asks the patient to save any passed stones for testing.

If the stone has not passed in 2 - 3 days, the patient will need additional treatments. In some severe cases, hospitalization may be necessary.

Specific procedures vary depending on the size of the stone or complexity of the situation. Noninvasive procedures are proving to be very beneficial in eliminating stones, and have largely replaced invasive surgeries.

For small stones that are lodged in the lower part of the ureter, ureteroscopy or shock wave lithotripsy are the procedures of choice.
For larger stones, ureteroscopy, percutaneous nephrolithotomy, and shock wave lithotripsy are all potentially useful. The choice of any of these procedures depends on a number of factors, including location of the stone and the presence of any problems that caused the stone in the first place.
In some complicated cases, standard open surgical procedures (called nephrolithotomy) may be required.

See "Other Treatments" section for more information on kidney stone surgery.


Stone Type	Diet and Lifestyle	Medications	Procedures
Calcium Oxalate	Plenty of fluids. (Choose water, lemon juice. Avoid grapefruit, apple, and cranberry juice.) Limit the amount of protein and salt in the diet. Increase fiber. Limit the amount of fats in the diet, particularly in people who have short bowel syndrome. Balance normal calcium intake with potassium- and phosphate-rich foods. Limit the amount of calcium in the diet (only in people who have genetic abnormalities that cause high intestinal absorption of calcium). Limit the amount of foods high in oxalates (only in patients with rare intestinal conditions that cause hyperoxaluria).	Diuretics ("water pills"), Citrate salts, phosphates, cholestyramine.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Uric Acid	Plenty of fluids. (Choose water, blackcurrant juice. Avoid cranberry juice.) Increase calcium intake (be sure well-balanced with potassium and phosphates). Reduce protein and other foods with high-purine content.	Potassium citrate, sodium bicarbonate, allopurinol.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Struvite stones	Plenty of fluids (water, cranberry juice). Reduce proteins.	Antibiotics to eliminate any infection. Acetohydroxamic acid (AHA) may be helpful in combination with antibiotics. In some cases, organic acids given through urinary tract.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.
Cystine stones	Very high fluid intake (four quarts a day). Limit the amount of protein in the diet.	Alkalizing agents (such as bicarbonate). Sometimes d-penicillamine, tiopronine, or captopril useful for lowering cystine levels.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.

Medications

Diuretics. Diuretics are medicines commonly used to treat high blood pressure and other disorders. They remove fluid and sodium from the body. Low doses of a class of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. Thiazides include:

Hydrochlorothiazide (Esidrix, HydroDiuril)
Chlorothiazide (Diuril)
Trichlormethiazide (Metahydrin, Naqua)
Chlorthalidone (Hygroton)

However, thiazides also cause potassium loss, which reduces citrate levels and can increase the risk for stones. Patients taking thiazide pills should also take potassium citrate, to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide does not work.

Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:

Potassium magnesium citrate is available over the counter. It is proving to be very beneficial in preventing kidney stones. In one study, potassium magnesium citrate reduced the risk for kidney stone recurrence by 85%.
Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) is given as the only treatment to people with normal urine calcium levels. Between 70 - 75% of patients with recurrent stones have ongoing remission (no stone recurrence) with potassium citrate treatment. However, some people cannot tolerate potassium citrate because of side effects (stomach problems).
Magnesium citrate (Citroma, Citro-Nesia) may help people who develop calcium stones from impaired intestinal absorption due to short bowel disease.

None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain this mineral or prevent its loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid citrate supplements, or discuss using non-tablet forms with their doctor.

Phosphates. Phosphates help reduce the breakdown of bone that releases calcium into the bloodstream. They are also involved in the kidney's reabsorption of calcium from the urine.

Phosphate compounds:

Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the doctor. Diarrhea is a possible side effect.
Cellulose phosphate (Calcibind) is recommended only for severe hypercalciuria that is associated with recurrent calcium stones and is caused by excessive absorption of calcium from the intestines. However, this drug may increase oxalate levels and decrease magnesium levels, which can lead to different stones. Taking magnesium supplements and reducing dietary oxalates, calcium, and ascorbic acid may help offset these risks. Cellulose phosphate may also cause bloating.

Avoid acidic forms of phosphate, since they increase the risks for both hypocitraturia and hypercalciuria.

Cholestyramine (Questran, Questran Light) is a drug used to reduce cholesterol levels. However, it also binds with oxalate in the intestine, so it is also used to reduce high oxalate levels in urine (hyperoxaluria). The drug usually comes in a powder that is dissolved in liquid.

Bloating and constipation are common side effects of this drug. Cholestyramine also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, take other drugs 1 hour before, or 4 - 6 hours after, taking cholestyramine.

Long-term use of cholestyramine may cause deficiencies of vitamins A, D, E, and K. Vitamin supplements may be necessary.

Sodium Bicarbonate. Patients whose persistently acidic urine causes uric acid stones may take sodium bicarbonate to reduce urine acidity. Patients taking sodium bicarbonate must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become too alkaline. This increases the risk for calcium phosphate stones. Patients who need to reduce the amount of sodium they take in (as a result of other medical conditions) should not use sodium bicarbonate.

Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.

Allopurinol. Allopurinol (Lupurin, Zyloprim) is very effective in reducing high levels of uric acid, and may be helpful for patients with uric acid stones. Allopurinol will not prevent calcium stones from forming. There is also a slight risk for the formation of xanthine stones with this drug. Side effects include diarrhea, headache, and fever. More severe complications include blood disorders that may produce fatigue, bleeding, or bruising. The drug may also increase the risk for cataracts.

About 2% of patients experience an allergic reaction to allopurinol that causes a rash. In rare cases, the rash can become severe and widespread enough to be life threatening. Allergic individuals who have experienced only a mild rash to sodium bicarbonate may be able to build up their tolerance for allopurinol by undergoing a desensitization process. In this process, patients start with small doses of allopurinol and gradually increase them, if no reaction develops.

Allopurinol reduces uric acid levels rapidly, so it may trigger an attack of gout in vulnerable people. To prevent this problem, patients taking allopurinol should also take a nonsteroidal anti-inflammatory drug (NSAID) for 2 or 3 months. Aspirin should not be taken, since it increases uric acid levels. Patients should discuss the appropriate NSAID choice with their doctor.

Before patients can receive any medical treatment for struvite stones, they must have surgery to completely remove the stones.

Antibiotics for Eliminating Infection. Persons with struvite stones receive ongoing treatment with antibiotics to keep the urine free of the bacteria that cause urinary tract infections. Careful follow-up and urine testing is extremely important. A high-pH urine indicates low acidity and an increased risk of infection.

Acetohydroxamic Acid (AHA). Acetohydroxamic acid (AHA or Lithostat) is beneficial when used with long-term antibiotics. AHA blocks enzymes that bacteria release, and has been effective in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron levels in the body, so anemia is a common problem. Patients may need to take iron supplements. Other side effects include nausea, vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs.

Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by specific struvite-causing organisms.

Patients taking this medicine should avoid alcohol. Pregnant women should not take acetohydroxamic acid.

Organic Acids. Medical treatments to dissolve stones may be useful in patients who do not respond to other medications, or in combination with surgeries. Acidic urine dissolves struvite stones, so the doctor may wash the urinary tract with a solution of organic acids (such as Renacidin). Candidates for such washes must have sterile urine (no bacteria or other organisms in the urine) and healthy kidney function. In surgical patients, the wash is performed 4 or 5 days after the operation. The wash starts with saline (salt solution) for 1 - 2 days and, if there are no problems, the organic acid solution follows for another 1 or 2 days, until all stones dissolve. Regular urine tests are necessary to ensure that the bacteria do not return.

Aluminum Hydroxide Gel. An aluminum hydroxide anti-acid gel may reduce phosphate levels that are important in struvite stone formation, but it has a long-term risk of causing aluminum toxicity. Long-term reduction of phosphorus can also increase the risk for calcium oxalate stones. Experts recommend limiting phosphorus through a low-protein diet, rather than through the use of this gel.

The first-line treatment for cystine stones is increasing the alkalization of urine so the stones can dissolve. If alkalization fails, drug treatments may include d-penicillamine, alpha-mercaptopropionylglycine (tiopronine), or captopril. These medications lower cystine concentration.

Patients with cystine stones must drink plenty of fluids, much more than patients with other stones. The patients should drink at least four quarts of water over a 24-hour period.

Other Treatments

Surgery is usually needed if the stone is too large to pass on its own, if there are signs that the stone is growing, or if the stone is blocking the urine flow and causing a urinary tract infection or kidney damage.

Until recently, the procedure to remove a stone was a very painful, major surgery, requiring 4-6 weeks of recovery. Today, treatments for stones are much less invasive. Major surgery is performed in less than 2% of patients.

Stone removal procedures:

Extracorporeal shock wave lithotripsy (ESWL) is used for small stones (less than one centimeter, or slightly less than half an inch) that occur in the upper part of the ureter and do not pass on their own. One study indicated lithotripsy might even be safe and effective for patients whose stones are associated with malformed kidneys, although such patients are at higher risk for stone recurrence and should be carefully monitored.
Percutaneous nephrolithotomy (PNL). PNL can be used for very large stones in the upper urinary tract, when ESWL fails, for kidney transplant patients, or when the kidneys or surrounding areas are malformed. PNL is the preferred procedure for drug-resistant cystine stones, which are usually also resistant to shock wave therapy.
Ureteroscopy. For stones in the lower tract, ureteroscopy is generally the best procedure, although lithotripsy is also usually feasible and patients ordinarily prefer it.
Standard open surgery (nephrolithotomy) may be required if any of these procedures fail or are not appropriate, or in special cases, such as when the patient is very obese.

Most procedures are more effective for calcium and uric acid stones and less effective for struvite and cystine stones, although new techniques may be improving their effects on all stones.

Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. ("Extracorporeal" means "outside the body," and "lithotripsy" means stone-breaking.) ESWL is not used for cystine stones. The procedure generally does not work for stones larger than three centimeters in diameter (which is slightly over an inch). There are several variations of ESWL. The following is a typical procedure:

Most ESWL procedures use some anesthesia, although they are often done on an outpatient basis.
The patient is positioned in a water bath. (In some procedures the patient lies on a soft cushion.)
The procedure uses ultrasound to generate shock waves that travel through the skin and body tissues until they hit the dense stones. (The doctor pinpoints the stone during treatment by using x-rays or ultrasound.)
The shock waves crush the stones into tiny sand-like pieces that usually pass easily through the urinary tract.
The shattered stone fragments may cause discomfort as they pass through the urinary tract. In such cases, the doctor may insert a small tube called a stent through the bladder into the ureter to help the fragments pass. This practice, however, has not proved to speed up passage of the stones in most cases and is not used routinely.

Extracorporeal shock wave lithotripsy (ESWL) is a procedure used to shatter simple stones in the kidney or upper urinary tract. Ultrasonic waves are passed through the body until they strike the dense stones. Pulses of sonic waves pulverize the stones, which are then more easily passed through the ureter and out of the body in the urine.

Success rates of ESWL range from 50 - 90%, depending on the location of the stone and the surgeon's technique and level of experience. Recovery time is short, and most people can resume normal activities in a few days.

Complications. Complications may include the following:

The most common complication is blood in the urine, which lasts for a few days after treatment. To reduce the chances of bleeding, doctors usually tell patients to avoid taking aspirin and other NSAIDs, which can promote bleeding, for 7 - 10 days before the treatment.
Bruising and minor discomfort due to the shock waves are common in the back or abdomen.
Sometimes the stone does not completely break up with one treatment, and additional treatments may be required. Inability to pass stone fragments may also be a particular problem in patients who have cysts or other kidney problems.
Higher risk for diabetes later. A 2006 study published in the journal Urology found that 17% of patients who received shock-wave lithotripsy developed diabetes later in life. The diabetes risk was related to the number and intensity of shocks.
Higher risk for hypertension (high blood pressure). The same study that linked ESWL to diabetes also showed that people who received shock-wave lithotripsy treatment were 47% more likely to develop high blood pressure than those who had their stones treated without surgery.

ESWL appears to be safe for children, although a 2001 study reported temporary damage in the kidney tubules after treatment. It is unclear if this complication has any long-term consequences. Experts recommend using the least amount of shocks and impact possible in young people. If more than one treatment is needed, there should be a waiting period of at least 15 days between treatments.

Percutaneous nephrolithotomy may be used when ESWL is not available or effective (such as if the stone is very large, in an inaccessible location, or is a cystine stone). It is also preferred over ESWL for stones that have remained in the ureter for more than 4 weeks.

It is more effective than ESWL for patients with severe obesity, and appears to be safe for the very elderly and the very young. Success rates are nearly 98% for kidney stones and 88% for ureteral stones. They may vary by the technique used and the specific patients. For example, success rates are slightly lower in children, although the procedure can be done safely in young patients. Long-term effects are unknown.

A typical procedure is as follows:

The surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney.
The surgeon then inserts an instrument called a nephroscope through the tunnel.
The stone is located and removed. If it is large, it is destroyed using ultrasound, lasers, or other devices. The surgeon then removes the fragments. An advantage of percutaneous nephrolithotomy over ESWL is that the surgeon is able to remove the stone fragments directly, instead of relying on their natural passage from the kidney.
Generally, patients stay in the hospital for 5 or 6 days and may need a small device called a nephrostomy tube left in the kidney during the healing process.

Devices Used to Destroy Stones. For large stones, some type of energy-delivering device may be needed to break the stone into small pieces. They are referred to as intracorporeal lithotripsy devices (meaning stone breakers within the body). The device may be one of the following:

Ultrasound is currently the preferred method. It results in a stone-free rate of 94%. A rigid nephroscope delivers the ultrasound waves.
Pneumatic (compressed air) lithotripsy uses a probe that comes in direct contract with a stone. Compressed air causes a piston to collide rapidly with the probe, and the result is a "jackhammer" action against the stone, causing the stone to break up. This method, however, can send stone fragments into other parts of the urinary tract.
A more recent device uses a combination pneumatic probe and ultrasound, with stone-free rates of 80 - 89%. It may prove to be superior to ultrasound alone and be effective against stones of all types.
The holmium laser literally melts the stones and destroys up to 100% of stones of any composition. It uses a flexible nephroscope and has an excellent safety record. It should be used sparingly, however, with particular caution against large uric acid stones until more is understood about its effect. Another device, the erbium: YAG laser, although showing promise in lithotripsy, is not currently practical.

Complications. Complication rates are about 3%. Major complications occur in about 1% of cases. These complications may include scarring of the tissue, but studies indicate that it does not impair kidney function, even if the patient requires repeat surgery. There is also a risk for blood loss during and after the procedure, which, in some cases, can be significant.

Because the procedure requires large volumes of fluid, fluid overload is a potential problem, particularly in children or patients with heart disease.

In some cases, infection may result. Other complications may include a collapsed lung and injuries to areas outside the kidney (but within the operative area), such as the abdomen or chest.

Ureteroscopy may be used for stones in the middle and lower ureter. With the arrival of smaller instruments, this procedure can be done successfully in children as well. The procedure involves the following:

The patient receives a general anesthetic, though no incision is required for the procedure.
The surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter.
The surgeon locates the stone or stones.
The surgeon can remove smaller stones by grasping them with small forceps. A laser or pneumatic device breaks up large stones.
The surgeon may decide to leave a small tube, or stent, in the ureter for a few days after treatment, to help the lining of the ureter heal.

Complication rates range from 10 - 20%, with major problems occurring in up to 6% of patients. In some cases, large stones are not broken up into small enough pieces. This can result in blockage of the urinary tract and possible kidney damage.

Imaging tests, such as ultrasound or spiral CT, are useful within 3 months to check for residual stones, and a second procedure may be required. The risk of complications is highest when the procedure is performed by less experienced surgeons, or if stones are found in the kidney. The risk for perforation of the ureter increases the longer the procedure takes.

Open surgery involves incisions through the patient's flank and into the kidney. The surgeon will cool the kidneys using ice. X-rays during the procedure help locate the stone. At the beginning of the surgery, the surgeon will isolate the arteries supplying the kidneys, ensuring they are not harmed during the surgery. The surgeon will then locate and remove the stone. The surgeon will also correct any blockage in the affected area. The surgery, called nephrolithotomy, is very invasive and is restricted to the following:

Patients with very large or complex stones that cannot be removed using less invasive measures
Very obese patients

Some centers report success with extracorporeal shock wave lithotripsy, however, in patients who would normally be nephrolithotomy candidates. Therefore, even these patients should discuss other options with their surgeon.

The procedure is not appropriate for patients with:

Bleeding or clotting disorders
Untreated widespread infection
Severe and chronic kidney insufficiency (unless removing the stone will improve kidney function)

Complications

Between 70 - 90% of crystals remain tiny enough so that they can travel through the urinary tract and leave the body in the urine without being noticed. When they do cause symptoms, however, kidney stones have been described as one of the most painful disorders to afflict humans. The pain they cause is sometimes called renal colic. ("Renal" means "kidney.")

Obstruction and Infection. Although kidney stones often lead to obstruction (blockage) of the urinary tract, the blockage is usually temporary and causes no lasting damage. In some cases, however, particularly if the obstruction progresses with no symptoms, infection may occur, which can be serious and need immediate attention.

Kidney Failure. It is very rare for kidney stones to cause kidney failure, although some people have risk factors that make them more vulnerable to this serious complication. Risk factors include the following:

Very frequent recurrences (such as in people with cystine stones or other inherited forms of kidney stone disorders)
Accompanying episodes of urinary tract infections with obstruction, a particular risk with struvite stones
A history of multiple urologic procedures for kidney stones
Greater size of the kidney stone gravel

Without preventive treatment, calcium stones recur in 10% of patients within a year of the first attack, and in half of patients within 5 - 7 years. Individual risk for recurrence, however, varies depending on the stone and the underlying condition. For example, a 15-year-old with inherited cystine stones has a very high risk for recurrence, while a middle-aged man with a first calcium oxalate stone has a good chance of never passing another.

Prevention

All individuals who have experienced kidney stones should take some specific preventive measures to prevent recurrence. The following are some general observations:

The most important dietary recommendations for reducing the risk for calcium stones are increasing fluid intake, restricting sodium, and reducing protein intake.
A lower risk for calcium stones is also associated with higher potassium intake.
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. (Increasing calcium alone may pose a modest risk for stones.)
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine, which promote stone formation.

Because different kidney stone types may require specific dietary changes, patients should work with their doctors to develop an individualized plan. It is important to note that nutritional considerations are very important in preventing recurrence, and patients should be vigilant in complying with the proper diet.

Good voiding habits, particularly frequent urination, are important. Therefore, of all the preventive recommendations, drinking enough fluids is the most important guideline for people with any type of kidney stones.

In general, patients with calcium or uric acid stones should drink at least 10 full glasses of fluid each day (at least half should be water). This includes one with each meal and drinking fluids at night, even if it means getting up from sleep. Fluid intake should produce at least two and a half quarts of urine each day.
To prevent cystine stones, patients should drink even more water -- over a gallon, or 16 8-ounce cups, every day. Patients should drink this amount at regular intervals throughout the night and day.

In all cases, patients need more fluid after exertion and during times of stress. If they drink enough, the urine should be pale and almost watery, not dark and yellow.

Water. Although water is best, it may vary depending on its source. Variations in water itself may have different impacts. One study reported that drinking hard tap water increased urinary calcium concentration by 50% compared to soft bottled water. On the other hand, mineral water containing both calcium and magnesium may reduce several risk factors for both calcium and uric acid stone formation.

Juices and Specific Effects. Other beverages have various positive or negative effects, depending on the type of stone:

Lemon Juice: Drinking one-half cup of pure lemon juice (enough to make eight glasses of lemonade) every day raises citrate levels in the urine, which might protect against calcium stones. (While orange juice also increases citrate levels, it does not lower calcium and it raises oxalate levels. Therefore, it is not recommended.)
Cranberry and Apple Juice: Apple and cranberry juice contain oxalates, and both have been associated with a higher risk for calcium oxalate stones. Cranberry juice has properties that may increase the risk for both calcium oxalate and uric acid stones. On the other hand, cranberry juice helps prevent urinary tract infections and so may be helpful for reducing the risk for struvite and brushite stones. (These stones are far less common, however.)
Black Currant Juice: In one study, black currant juice reduced urine acidity and was associated with protection against uric acid stones.
Grapefruit Juice: A number of studies have found a risk for stones from drinking grapefruit juice. In one study, just one 8-ounce cup of grapefruit juice per day increased the risk for forming stones by 44%.

Other Beverages and Their Effects on Stone Formation.

Soft Drinks. Patients with stones should avoid cola drinks, since they can severely reduce citrate levels in the urine. Many soft drinks contain phosphoric acid, which increases the risk for stones. Some research shows that drinking one quart (less than three 12-ounce cans) of soda per week may increase a person's risk of developing stones by 15%.
Alcohol. Wine may be protective against kidney stones. A study conducted in Finland, suggests that the risk of developing stones also decreases with beer consumption. However, it is important to remember that beer is high in oxalates. Beer and other alcoholic beverages also contain purines, which may increase the specific risk for the less common uric acid stones in susceptible people. Binge drinking, in any case, increases uric acid and the risk for stones.
Coffee and Tea. Some research reported a lower risk for stones in people who drink tea and both regular and decaffeinated coffee.

A long-term 2002 study followed men with calcium oxalate stones and high levels of urinary calcium. The study found that a low-sodium, low-protein diet, containing normal levels of calcium, dramatically reduced the recurrence of stones compared to a diet that was simply low in calcium.

Salt Restriction. Because salt intake increases the amount of calcium in urine, patients with calcium stones should limit their sodium intake. Sodium may also increase levels of urate, the crystalline substance that can trigger formation of recurrent calcium oxalate stones. Although the relative contribution of limiting sodium intake has not been confirmed, some researchers believe that restricting sodium along with increasing fluid intake is the most important dietary measure for preventing stones.

Protein Restriction. Protein increases uric acid, calcium, and oxalate levels in the urine, and reduces citrate levels. Diets high in protein, particularly meat protein, have been consistently connected with kidney stones. (Meat protein has a higher sulfur content and produces more acid than vegetable protein.) A 2002 study of those following a high-protein, low-carbohydrate diet (such as the Atkins diet, for example), found dramatically increased levels of urinary uric acid and calcium after just several weeks. These effects put patients at higher risk for not just kidney stones, but possibly osteoporosis as well. According to Swiss studies, about a third of people at risk for calcium stones may have a sensitivity to meat proteins that causes mild hyperoxaluria.

Whether restricting meat protein alone has any protective value without restricting sodium as well is unknown. Most studies to date have found no difference in stone development between people with low and normal meat protein diets over four years. A 2000 study reported that only dramatic reductions in meat protein had any preventive effect against stone recurrence.

Although the precise role of dietary protein in kidney stones needs further clarification, it is reasonable for everyone to consume meat protein in moderation. People with struvite stones, who need to reduce phosphates in their diets, should also cut down on proteins.

Calcium from Foods. Dietary calcium recommendations for kidney stone prevention need to be determined on an individual basis. A doctor will suggest calcium guidelines based on a patient's age, gender, body size, and type of stone. Most studies indicate that dietary calcium (found in milk, yogurt, and cheese) protects against many types of calcium oxalate stones. Large studies of both men and women found that those with the highest intake of calcium from foods had a much lower risk for stones than those who had little calcium in their diets. A diet containing a normal amount of calcium, but reduced amounts of animal protein and salt, may protect against stones better than a low-calcium regimen. However, calcium metabolism changes as people age. Some studies suggest that a high calcium intake protects against kidney stones in men younger than age 60, but not in older men.

Dietary calcium may actually bind the oxalate in foods, preventing it from being absorbed into the blood and excreted into the urine. In a normal healthy diet, dairy products supply almost 80% of the daily calcium requirement. For people who have calcium stones associated with resorption (the breakdown of bone that releases calcium into the bloodstream), limiting calcium intake could cause further bone loss.

Calcium Supplements. Evidence on calcium supplements is mixed, although in general many studies suggest that they reduce oxalate levels and so help prevent calcium oxalate stones. One study suggested that taking 500 mg of calcium supplements a day regularly may "reprogram" the intestines to absorb less calcium and may therefore be protective. Experts generally agree that calcium supplementation within dosage recommendations (about 1,200 mg per day) remains safe. In one study, however, women who took calcium supplements had a 20% higher risk for stones. Research indicates that dosages of calcium above 2,000 mg per day are clearly associated with the formation of stones. Some experts speculate that this higher risk may occur because supplements are often taken in the morning, either without food or with breakfast, which is typically low in oxalates. Taking supplements with later meals may not produce the same risk.

Calcium Restriction in Certain Cases. Some patients, such as those whose stones are caused by genetic defects in which the intestine absorbs too much calcium, may need to limit calcium intake. More studies are needed to define this group precisely.

Fiber may be beneficial for people with kidney stones. In addition, some fiber-rich foods may contain compounds that help protect against kidney stones. A wide variety of high-fiber plant foods contain a compound called phytate (also called inositol hexaphosphate, InsP6, or IP6), which appears to help prevent crystallization of calcium salts, both oxalate and phosphate. Phytate is found in legumes and wheat and rice bran. (Soybeans are also rich in phytate but they are also very high in oxalates, so the overall effects of soy on kidney stones are not clear.)

A high intake of purines can increase the amount of uric acid in the urine. Those at risk for uric acid stones should reduce their intake of foods and beverages that contain purines. These include beer and other alcoholic beverages, anchovies, sardines, yeast, organ meats (such as liver and kidneys), legumes (including dried beans, peas, and soybeans), mushrooms, spinach, asparagus, cauliflower, and poultry.

Most people with calcium oxalate stones should not avoid oxalate-rich foods unless the doctor specifically recommends a restrictive diet. Oxalate binds with calcium in the intestine, which may actually reduce calcium absorption. Some studies, in fact, indicate that eating foods containing oxalates and calcium together may reduce the risk of stones. Most of the foods that contain oxalates are very important for good health. Limiting oxalates may be particularly harmful in people with bowel disorders marked by malabsorption.

Foods high in oxalic acid include beets, soy, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard.
Foods containing moderate amounts of oxalates include beans (green and wax), blackberries, blueberries, carrots, celery, coffee (roasted), concord grapes, currants, dandelion greens, endive, gooseberries, lemon peel, okra, green onions, oranges, green peppers, black raspberries, strawberries, and sweet potatoes.

Certain fats may play a beneficial or harmful role in specific cases of kidney stones.

Restricted Fats in Patients with Stones Associated with Bowel Disease. Patients who have stones associated with short-bowel syndrome should eat foods with lower amounts of fats and oxalates. If patients with short-bowel syndrome eat too much fat, calcium may bind to unabsorbed fat instead of to oxalates. This increased oxalate levels, resulting in increased risk of stone formation.

Fish Oil. Omega-3 fatty acids, found in oily fish like mackerel, salmon, and albacore tuna, have many health benefits, but the most current evidence suggests they do not help prevent kidney stones. A 2005 study of over 200,000 adults found that increased omega-3 fatty acid intake did not reduce kidney stone risk.

Vitamin B6. Vitamin B6, or pyridoxine, is used to treat people with primary hyperoxaluria, a severe inherited disorder. Patients should not try to treat themselves with vitamin B6. Very high doses (500 to 2,000 mg daily over long periods) can cause nerve damage, with loss of balance and numbness in the feet and hands. Food sources of vitamin B6 include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.

Vitamin C. Ascorbic acid (vitamin C) may change in the body to tiny crystals, called oxalates. These crystals do not dissolve. People with hyperoxaluria (too much oxalate in the urine) should avoid vitamin C supplements. Even for men with normal oxalate levels, higher consumption of vitamin C (more than 1,000 mg a day) may increase kidney stone risk.

Magnesium and potassium may help reduce the risk for kidney stones in men.

Because of an association between stress and kidney stones, relaxation and stress management techniques may also be beneficial.

Dietary Considerations. People with kidney stones appear to be more sensitive to certain foods than people who do not form kidney stones. Therefore, vulnerable people should make specific changes in their diet. They should work with their doctors to develop a dietary plan that fits their individual situation. Drinking plenty of fluids is important for preventing recurrence of any kidney stone.

Indications for Drug Treatments. If dietary treatments fail, drug therapy may be helpful. A number of drugs are available to prevent recurrences of calcium oxalate and other stones. Medications that inhibit the formation of stones include allopurinol, thiazide, potassium citrate, and potassium-magnesium citrate. In addition, drug treatments can sometimes also help prevent other complications related to stones, such as osteoporosis.

Correcting Underlying Conditions Known to Cause Kidney Stones. It is also important to treat and correct, if possible, any underlying disorder that may be causing stones to form. Such disorders include distal renal tubular acidosis, hyperthyroidism, sarcoidosis, and certain cancers. To prevent calcium stones that form in hyperparathyroid patients, a surgeon may remove the affected parathyroid gland (located in the neck). In most cases, only one of the glands is enlarged. Removing it ends the patient's problem with kidney stones.

Resources

www.kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Information Clearinghouse
www.urologyhealth.org -- American Urological Association
www.kidney.org -- National Kidney Foundation
www.ohf.org -- Oxalosis and Hyperoxaluria Foundation

References

Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric Acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422-8. Epub 2006 Apr 5.

Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(:885-891.

Finkielstein VA. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10); 1407-1409.

Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol. 2006;175(5):1742-7.

Sinha MK, Collazo-Clavell ML, Rule A, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney International. 2007;72:100-107.

Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005;15(2):119-126.

Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232.

Taylor EN, Stampfer MJ, Curhan GC. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005;45(2):267-274.

Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462.

Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005 Sep;68(3):1230-5.

Wasserstein AG. Nephrolithiasis. American Journal of Kidney Diseases. 45(2);2005:422-28.

Review Date:
7/24/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Allopurinol (Injection)

admin — Thu, 04 Sep 2008 19:57:33 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
How to Store and Dispose of This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Allopurinol (al-oh-PURE-i-nole)

Treats elevations of uric acid in blood and urine.

Brand Name(s)

Aloprim

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not use this medicine if you have ever had an allergic reaction to allopurinol.

How to Use This Medicine

Injectable

Your doctor will prescribe your exact dose and tell you how often it will be given.
Drink 10 to 12 full glasses of liquids each day unless directed differently by your doctor.
Your medicine will be given directly into a vein, usually in your arm or chest. This is called intravenous (in-tra-VEN-us), or IV.
A nurse or other caregiver trained to give IV medicines will give your treatment.

If a dose is missed:

If you miss a dose, call your doctor, home health caregiver, or clinic where you get treatments for instructions.

How to Store and Dispose of This Medicine

If your have your treatments at a clinic, the staff at the clinic will keep your medicine there.
If you have your treatments at home, you should be given a special container for the used needles, medicine bottles, and tubes. Put it where children or pets cannot reach it.
If you have your treatments at home, you may need to store your medicine. You should store the unopened bottles at room temperature, away from heat, moisture, and direct light. Store mixed or prepared medicine at room temperature, away from heat, moisture, and direct light.
Keep all medicine out of the reach of children.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

Make sure your doctor knows if you are using blood thinners (such as Coumadin®), diuretics (such as hydrochlorothiazide), ampicillin, amoxicillin, cyclosporine, azathioprine (Imuran®), or mercaptopurine (Purinethol®).
Avoid taking large doses of vitamin C while you are using this medicine.

Warnings While Using This Medicine

Check with your doctor before using this medicine if you have diabetes, high blood pressure, heart failure, seizures, kidney disease, liver disease, or other medical problems.
If you are pregnant or breastfeeding, talk with your doctor before using this medicine.
This medicine may make you drowsy. Be careful when driving a car or using machinery.
Stop using allopurinol and call your doctor right away if you notice a skin rash, pain when you use the bathroom (urinate), blood in your urine, irritation of your eyes, or swelling of your lips or mouth.
Your doctor may want to test your blood while you are using this medicine. Be sure to keep all appointments.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Burning or peeling of skin
Joint pain or muscle aches
Skin rash, redness, itching or hives
Trouble breathing
Unexplained chills, fever, or sore throat
Yellow skin or eyes

If you notice these less serious side effects, talk with your doctor:

Drowsiness
Headache
Loss of appetite or weight loss
Nausea, vomiting, or diarrhea

Review Date: 8/4/2008

A.D.A.M. Copyright

adam.com

Source Doc: 45_0945

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

adam.com

Urinary tract infection

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Urinary Tract Infections (UTIs) in the United States

According to Urologic Diseases in America, a report published in 2007 by the U.S. National Institutes of Health:

UTIs are the most expensive of all urologic diseases, accounting for about $3.5 billion a year in medical costs, including $96.4 million in prescriptions.
Over 60% of women will experience a UTI at least once in their lifetime. At least a third of women experience a UTI by the time they are 24 years old.
Only 20% of UTIs occur in men. However, men are far more likely than women to be hospitalized for an infection.
Childhood risk for UTIs is 2% for boys and 8% for girls. Vesicouretereal reflux, a condition in which urine backs up into the kidneys, affects about 10% of all children.

Circumcision Prevents UTIs

Baby boys who are uncircumcised are 10 - 12 times more likely than circumcised boys to develop UTIs during their first year of life, indicates the Urologic Diseases in America report.

High Doses of Zinc Increase UTI Risk

People who take very high daily doses of zinc supplements may face an increased risk for UTIs and other urologic problems, suggests a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc.
In general, the upper limit for zinc supplements should not exceed 40 mg/day. Eight mg/day for women and 11 mg/day for men are the recommended average doses. However, very high doses of zinc are sometimes prescribed for certain medical conditions, such as age-related macular degeneration.

Introduction

A urinary tract infection (UTI) is a condition where one or more structures in the urinary tract become infected after bacteria overcome its strong natural defenses. In spite of these defenses, UTIs are the most common of all infections and can occur at any time in the life of an individual. Almost 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder (known as the ascending route). Much less often, bacteria spread to the kidney from the bloodstream.

The male and female urinary tracts are relatively the same except for the length of the urethra.

Different classifications have been devised to help doctors choose treatments and determine the causes of UTIs.

Primary or Recurrent UTIs. UTIs are classified as primary or recurrent, depending on whether they are the first infection or whether they are repeat events.

Community- or Hospital-Acquired. UTIs are also sometimes grouped according to where they are acquired:

Community-Acquired Infections. Most UTIs are thought to develop in the community at large. It is unclear how primary community-acquired infections occur or how they are spread. Although most cases have been thought to arise sporadically, a rare outbreak in 1996 - 2000 caused by drug-resistant bacteria suggests epidemic spread of community-acquired infections could be more common than previously thought and may be spread via contaminated food. Most community-acquired infections are not serious and probably develop when the intestines become colonized with bacteria that are also predisposed to infecting the urinary tract.
Hospital-Acquired Infections. UTIs are also commonly acquired in the hospital, often due to contaminated urinary catheters. Hospital-acquired infections (known as nosocomial infections) tend to be more serious because the bacteria that cause them are often resistant to drug treatment and patients are often in poor general health.

Uncomplicated and Complicated. UTIs are also sometimes further defined as either being uncomplicated or complicated depending on the factors that trigger the infections.

Uncomplicated infections are only associated with bacterial infection, most often Escherichia coli (E. coli). They affect women much more often than men.
Complicated infections, which occur nearly as often in men as women, are also caused by bacteria but they occur as a result of some anatomical or structural abnormality. Often they are associated with catheter use in the hospital setting, bladder and kidney dysfunction, or kidney transplant (especially in the first three months after transplant). Recurrences occur in up to 50 - 60% of patients with complicated UTI if the underlying structural or anatomical abnormalities are not corrected.

Classifications Based on Symptoms and Levels of Infection. UTIs can also occur without symptoms and with symptoms but very low bacterial levels.

When bacteria are present and there are no symptoms it is called asymptomatic UTI or also bacteriuria.
Some patients can also have symptoms of infection with very low bacterial counts. In such cases, the condition is called acute urethral syndrome.

Cystitis. Cystitis is the most common urinary tract infection and is sometimes referred to as acute uncomplicated UTI. It occurs in the lower urinary tract (the bladder and urethra) and nearly always in women. In most cases, the infection is brief and acute and only the surface of the bladder is infected. Deeper layers of the bladder may be harmed if the infection becomes persistent, or chronic, or if the urinary tract is structurally abnormal.

Pyelonephritis (Kidney Infection). When infection spreads to the upper tract (the ureters and kidneys) it is called pyelonephritis, or more commonly, kidney infection. As many as half of all women with cystitis may have infections of the upper urinary tract at the same time as cystitis.

Click the icon to see an image of the kidney.

Urethritis. When infection is limited only to the urethra, the infection is known as urethritis. This is a common sexually transmitted disease in men.

Complicated UTIs may develop because of any one of a number of physical problems and affect any gender and age group. The common feature in most complicated UTIs is the inability of the urinary tract to clear out bacteria because of a physical condition that causes obstruction to the flow of urine or problems that hinder treatment success.

Most women who have had an uncomplicated UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one. Between 3 - 5% of women have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode.

Recurrence is often categorized as either reinfection or relapse:

Reinfection. About 80% of recurring UTIs are reinfections. A reinfection occurs several weeks after antibiotic treatment has cleared up the initial episode and can be caused by the same bacterial strain that caused the original episode or a different one. The infecting organism is usually introduced through the rectal region from fecal matter and moves up through the urinary tract.
Relapse. Relapse is the less common form of recurrent urinary tract infection. It is diagnosed when a UTI recurs within 2 weeks of treatment of the first episode and is due to treatment failure. Relapse usually occurs in kidney infection (pyelonephritis) or is associated with obstructions such as kidney stones, structural abnormalities or, in men, chronic prostatitis.

When a person has no symptoms of infection but significant numbers of bacteria have colonized the urinary tract, the condition is called asymptomatic UTI (also called asymptomatic bacteriuria). (In general, there must be at least 100,000 bacteria per milliliter of urine.) The condition is harmless in most people and rarely persists, although it does increase the risk for developing symptomatic UTIs.

Screening for asymptomatic bacteriuria is not necessary during most routine medical examinations, with the following exceptions:

Pregnant women. Pregnant women with asymptomatic bacteriuria have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore, they need screening and treatment for this condition.
People undergoing urologic surgery (such as prostate surgery in men). The presence of an infection during surgery can lead to serious consequences.

Some groups recommend screening women with diabetes for asymptomatic bacteriuria. However, a 2003 study suggested that treating women who test positive for this condition does not reduce their risk of complications from UTIs. Asymptomatic bacteriuria may be an indicator for serious health problems in the elderly, but screening for the condition is not warranted in this group.

Some people have symptoms of cystitis but have a bacterial count lower than that ordinarily found in UTI. Such patients are sometimes diagnosed with acute urethral syndrome. This condition is usually caused by E. coli or other bacteria that cause cystitis, but in lower numbers, or by a sexually transmitted disease such as Chlamydia or gonorrhea.

Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. The average age of patients with IC is 40 years, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. These women often complain of experiencing pain during sex. Pelvic pain, depression, and stress may intensify symptoms. Women with IC also frequently suffer from other conditions, including allergies, urinary incontinence, sinusitis, and irritable bowel syndrome (IBS). Some doctors think that IC may be related to autoimmune diseases such as fibromyalgia and lupus.

IC is difficult to diagnose and treat. Pentosan (Elmiron) is the most frequent drug treatment, but doctors prescribe other medications as well (see Medications section). Some evidence suggests that diet can worsen IC symptoms. For instance, patients should avoid coffee (both caffeinated and decaf), alcohol, cola, vinegar, citrus fruits, tomatoes, chili, strawberries, pineapple, onions, pizza, chocolate, and apples, according to research presented at the 2006 American Urological Association scientific meeting.

The Urinary System. The urinary system helps maintain proper water and salt balance throughout the body and also expels urine from the body. It is made up of the following organs and structures:

The two kidneys, located on each side below the ribs and toward the middle-back, play the major role in this process. They filter waste products, water, and salts from the blood to form urine.
Urine passes from each kidney to the bladder through thin tubes called ureters.
Ureters empty into the bladder, which rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine, which is then eliminated from the body via another tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)

Defense Systems Against Bacteria. Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria:

Urine itself functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.)
The ureters are structurally designed to prevent urine from backing up into the kidney.
The prostate gland in men secretes infection-fighting substances.
The immune system in both sexes continuously fights bacteria and other harmful micro-invaders. In addition, immune system defenses and antibacterial substances in the mucous lining of the bladder eliminate many organisms.
In normal fertile women, the vagina is colonized by lactobacilli, beneficial microorganisms that maintain a highly acidic environment (low pH). Acid is hostile to other bacteria. Lactobacilli also produce hydrogen peroxide, which helps eliminate bacteria and reduces the ability of E. coli to adhere to vaginal cells. (E. coli is the major bacterial culprit in urinary tract infections.)
Some interesting research suggests that when bacteria infect the bladder, the cells that line the bladder literally sacrifice themselves and self-destruct (a process called apoptosis). In so doing, they fall away from the lining, carrying the bacteria with them. This eliminates about 90% of the E. coli.
Some researchers have identified a possible natural antibiotic called human beta-defensin-1 (HBD-1), which fights E. coli within the female urinary and reproductive tracts.

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

Causes

The bacterial strains that cause UTIs include:

Escherichia (E.) coli is responsible for 75 - 90% of uncomplicated cystitis cases in younger women and in more than half the cases in older women (over age 50). In most cases of UTI, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage, where it invades and colonizes the urinary tract. Some bacteria may be able to invade into deeper tissue in the bladder, where they survive to reinfect the patient after resolution of the previous infection.
Staphylococcus saprophyticus accounts for 5 - 15% of UTIs, mostly in younger women. Infections caused by this bacterium tend to have a seasonal variation, with a higher incidence in the summer and fall than in the winter and spring.
Klebsiella, Enterococci bacteria, and Proteus mirabilis account for most of remaining bacterial organisms that cause UTIs. They are generally found in UTIs in older women.
Rare bacterial causes of UTIs include ureaplasma urealyticum and Mycoplasma hominis, which are generally harmless organisms.

The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence, however, the E. coli strains in pyelonephritis are more virulent (able to spread and cause illness).
Complicated UTIs that are related to physical or structural conditions are apt to be caused by a wider range of organism. E. coli is still the most common organism, but others have also been detected, including Klebsiella, P. mirabilis, and Citrobacter.
Fungal organisms, particularly Candida species. (Candida albicans, for example, causes the so-called "yeast infections" that also occur in the mouth, digestive tract, and vagina.)
Other bacteria associated with complicated or severe infection include Pseudomonas aeruginosa, Enterobacter, and Serratia species, gram-positive organisms (including Enterococcus species), and S. saprophyticus.

Recurring infections are often caused by different bacteria than those that caused a previous or first infection.

Even if the reinfecting bacterium is still E. coli, it may be a variant of the original infecting E. coli strain. Such strains produce substances, such as one called P fimbriae, which tend to make the bacteria more infectious. Uncommon causes of reinfection include Ureaplasma and Mycoplasma hominis, which are sometimes associated with acute urethral syndrome.

The bacteria that cause most UTIs are very common. Nearly everyone harbors them. It is not clear how they proliferate and break down the natural defenses of the body. Among the possible ways this occurs are:

Changes in the Acid-Alkaline Balance of the Urinary Tract. Changes in the amount or type of acid within the genital and urinary tracts are major contributors to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the urinary tract. Reductions in their number (which, for example, occurs with estrogen loss after menopause), increases pH and therefore the risk of infection.

Biofilm. One theory, called the biofilm mode of growth, suggests that sometimes bacteria form capsules that adhere to the urinary tract, protecting them from many of the body's normal defenses.

Symptoms

Symptoms of lower urinary tract infections usually begin suddenly and may include one or more of the following signs:

The urge to urinate frequently, which may recur immediately after the bladder is emptied.
A painful burning sensation. (If this is the only symptom, then the infection is most likely urethritis.)
Discomfort or pressure in the lower abdomen. The abdomen can feel bloated.
Cramping in the pelvic area or back.
The urine often has a strong smell, looks cloudy, or contains blood. This is a sign of pyuria, or a high white blood cell count in the urine, and is a very reliable indicator of urinary tract infections.
Occasionally, fever develops.

Symptoms of kidney infections tend to affect the whole body and be more severe than those of cystitis. They may include:

Symptoms of lower UTIs that persist longer than a week. (Sometimes lower UTI symptoms may be the only signs of kidney infection. People at highest risk for such "silent" upper urinary tract infections include patients with diabetes, impaired immune systems, or a history of relapsing or recurring UTIs.)
An increased need to urinate at night.
Chills and persistent fever (typically lasting more than 2 days).
Pain in the flank (pain that runs along the back at about waist level).
Vomiting and nausea.

UTIs in infants and preschool children tend to be more serious than those that occur in young women, in part because they are more likely to occur in the kidneys and upper urinary tract. (Older children are more likely to have lower urinary tract infections and standard symptoms.) Infants and young children should always be checked for UTIs if the following symptoms are present:

A persistent high fever of otherwise unknown cause, particularly if it is accompanied by signs of feeding problems and debility, such as listlessness and fatigue. (Studies have reported that up to 5% of infants and toddlers who are brought to the emergency room with fevers have UTIs. Scarring is a risk so very young children with UTIs need to be screened.)
Painful, frequent, and foul smelling urine. (Parents are generally unable to identify a UTI just by the smell of their child's urine. Medical tests are needed.)
Cloudy urine. (If the urine is clear, the child most likely has some other ailment, although it is not absolute proof that the child is UTI-free.)
Abdominal and low back pain may be present.
Vomiting and abdominal pain (usually in infants).
Jaundice (yellowing of the skin and the whites of the eyes) in infants, particularly if it develops after 8 days of age.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing the skin and whites of the eyes to have a yellowish appearance. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older patients with UTIs. In one study, only 20% of these patients had new urinary complaints, and many have no symptoms at all.

Symptoms of UTIs that may occur in seniors but not in younger adults may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. Concomitant illness may further confuse the picture and make diagnosis difficult.

Risk Factors

After the flu and common cold, urinary tract infections (UTIs) are the most common medical complaint among women in their reproductive years. Women are 30 times more likely to have UTIs than men. At least a third of American women are diagnosed with a UTI by the time they are 24 years old. Every year, 11% of American women have at least one such infection, and up to 60% of all women will develop a UTI at some time in their lives. A third of these women will have a recurrence within a year. Furthermore, each year about 250,000 women develop kidney infections (pyelonephritis) and 100,000 are hospitalized for treatment.

According to a 2007 report from the U.S. National Institutes of Health, urinary tract infections in both women and men are the most expensive of all urologic problems. Nationally, UTIs account for about $3.5 billion a year in medical costs.

Structure of the Female Urinary Tract. In general, the higher risk in women is mostly due to the shortness of the female urethra, which is 1.5 inches compared to 8 inches in men. Bacteria from fecal matter can be easily transferred to the vagina or the urethra.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Sexual Behavior. Frequent or recent sexual activity is the most important risk factor for urinary tract infection in young women. Nearly 80% of all urinary tract infections occur within 24 hours of intercourse. (Sexual activity is less associated with cystitis in women after menopause.)

UTIs are very rare in celibate women. It is important to stress, however, that UTIs are NOT sexually transmitted infections, although these infections ( Chlamydia trachomatis, gonorrhea, or herpes simplex virus) may increase the risk for UTIs.

In general, however, it is the physical act of intercourse itself that produces conditions that increase susceptibility to the UTI bacteria, with some factors increasing the risk:

Women having sex for the first time or who have intense and frequent sex after a period of abstinence are at risk for a condition called "honeymoon cystitis."
A sudden increase in the frequency of sexual intercourse poses a significant risk for UTI, particularly if a diaphragm is used.
Sexual position (such as the woman on top) can contribute to the risk.

Click the icon to see an image of a diaphragm.

Contraceptives may also contribute to risk in a number of ways:

The spring-rim of the diaphragm may bruise the area near the bladder neck, making it susceptible to bacteria.
Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections. (Using a sterile water-based lubricant, such as KY jelly, may help reduce this risk. Petroleum-based lubricants should be avoided because they weaken latex condoms.)
Some women experience UTI as an allergic reaction to latex in condoms or to oral contraceptives.
Use of spermicide, such as nonoxynol-9, doubles or triples a women's risk for UTI, regardless of whether it is used with a condom or diaphragm. Spermicides also pose a risk for sexually transmitted infections, and experts warn against their use.

Pregnancy. Although pregnancy does not increase the rates of asymptomatic bacteriuria, it does increase the risk that it will progress to a full-blown infection. About 2 - 11% of pregnant women have asymptomatic bacteriuria and, of those, 13 - 27% will develop a kidney infection late in their term. (However in early pregnancy, frequent urination -- a common symptom of UTI -- is most likely due to pressure on the bladder.)

Although all pregnant women should be tested for UTIs, women at highest risk have the following conditions or situations:

Diabetes
Sickle cell trait
Low-income
Have had many children
History of childhood UTIs
Have undergone a cesarean section with catheterization of the bladder
Have received epidural anesthesia

Women who have had a UTI before or during pregnancy also have a higher risk of developing recurrent urinary tract infections after delivery. About 25 - 33% of women who experience bacteriuria during pregnancy will have another urinary tract infection, sometimes as many as 10 - 14 years later.

Menopause. The risk for UTIs, both symptomatic and asymptomatic, is highest in women after menopause. Studies indicate that between 20 - 25% of women over 65 years old have UTIs, and 10 - 15% have asymptomatic bacteriuria (compared to 2 - 5% of young women). Sexual activity plays a lesser role in UTIs in older women than in younger women. In general, biologic changes due to menopause put older women at particular risk for primary and recurring UTIs:

With estrogen loss, the walls of the urinary tract thin, weakening the mucous membrane and reducing its ability to resist bacteria. The bladder may lose elasticity and fail to empty completely.
Estrogen loss has also been associated with reduction in certain immune factors in the vagina that help block E. coli from adhering to vaginal cells.
Levels of lactobacilli (protective bacteria) decline after menopause, perhaps also due to drops in estrogen.

Some women carry the blood group P1, which, as they get older, is associated with high levels of specific cells in the vagina and urethra that bind to a specific strain of E. coli that is resistant to normal infection-fighting mechanisms.

Other Risk Factors in Women. Women who have skin allergies to ingredients in soaps, vaginal creams, bubble baths, or other chemicals that are used in the genital area are at high risk for UTIs. In such cases, the allergies may cause small injuries that can introduce bacteria.

Most women who have had one UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one.

Between 3 - 5% of women, however, have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode. The major groups of women who are at highest risk for recurrent infections are young highly sexually active women and postmenopausal women. It might be argued that nearly all women who have a urinary tract infection are at risk for another, particularly if they are not treated for the first one.

Lifestyle Factors Increasing the Risk for Recurrence. Why urinary tract infections become chronic and recurring in many women is not entirely clear, but researchers are identifying certain lifestyle factors that may increase the risk in specific women:

Engaging in sexual intercourse more than four times a month.
Recent changes in sexual partners.
Having a mother with a history of UTIs.
Having a first UTI before age 15.
Use of spermicides.
Smoking and taking tub baths may also increase the risk for recurrent urinary tract infections, but they are less significant than other risk factors.

Biologic and Physical Factors. Some women may also have certain biologic or anatomical factors that increase the risk for recurring UTIs:

Having a shorter than average distance between the urethra and the anus.
Certain women may carry a compound called sialosyl galactosyl globoside (SGG) on the surface of kidney cells, which is a highly powerful receptor for E. coli bacteria.
Certain women have a genetic susceptibility to becoming infected in the vaginal area with greater numbers of disease-causing organisms that adhere to the lining.
Certain women may be deficient in human beta-defensin-1 (HBD-1), believed to be a naturally occurring antibiotic.

Risk Factors for Recurrence in the Aging Woman. In addition to menopause, other very strong risk factors for recurrences in older women include urinary incontinence and previous operations on the genital or urinary tracts. Additional risk factors for UTIs in older women include diabetes, vaginal itching or dryness, having had children, and poor overall health.

Each year, about 3% of American children develop urinary tract infections. During the first few months of life, UTIs are more common in boys than in girls. Boys who are uncircumcised are about 10 - 12 times more likely than circumcised boys to develop UTIs by the time they are 1 year old. After the age of 2 years, UTIs are far more common in girls. Throughout childhood, the risk of UTIs is about 2% for boys and 8% for girls. As with adults, Escherichia coli (E. coli) is the most common cause of UTIs in children.

Vesicoureteral Reflux (VUR). Vesicoureteral reflux (VUR) affects about 10% of all children. It is the source of urinary tract infections in 30 - 50% of childhood cases. This is a structural defect of the valve-like mechanism between the ureter and bladder that allows urine to flow backward, carrying infection from the bladder up into the kidneys. VUR also puts children at risk for recurrence. Such recurrences nearly always occur within the first 6 months after the first UTI.

Click the icon to see an image of vesicoureteral reflux.

Men become more susceptible to UTIs after 50 years of age, when they begin to develop prostate problems. Benign prostatic hyperplasia (BPH), enlargement of the prostate gland, can produce obstruction in the urinary tract and increase the risk for infection. In men, recurrent urinary tract infections are also associated with prostatitis, an infection of the prostate gland that is caused by E. coli. Although only about 20% of UTIs occur in men, these infections can cause more serious problems than they do in women. Men with UTIs are far more likely to be hospitalized than women. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Hospitalizations and Catheters. About 40% of all infections that develop in hospitalized patients are in the urinary tract. The organisms that cause infections in hospitals (called nosocomial infections) are usually different from those that commonly cause UTIs. They are also more likely to be resistant to standard antibiotics. Hospitalized patients at highest risk for such infections are those with in-dwelling urinary catheters, patients undergoing urinary procedures, long-stay elderly men, and patients with severe medical conditions.

About 80% of UTIs in the hospital are due to catheters. Nearly all patients who need urinary catheters develop high levels of bacteria in their urine, and the longer the catheter is in place, the higher the risk for infection. Catheterized patients who develop diarrhea are nine times more likely to develop UTIs than are patients without diarrhea. In most cases of catheter-induced UTIs, the infection produces no symptoms. Because of the risk for wider infection, however, anyone requiring a catheter should be screened for infection. Catheters should be used only when necessary and should be removed as soon as possible.

Nursing Homes. All older adults who are immobilized, catheterized, or dehydrated are at increased risk for UTIs. Nursing home residents, particularly those who are incontinent and demented, are at very high risk. Up to 40% of elderly patients who live in nursing homes will contract a urinary tract infection.

Some people have structural abnormalities of the urinary tract that cause urine to stagnate or flow backward into the upper urinary tract. Such conditions include:

A prolapsed bladder (cystocele) can result in incomplete urination so that urine collects, creating a breeding ground for bacteria.
Tiny pockets called diverticula sometimes develop inside the urethral wall and can collect urine and debris, further increasing the risk for infection.

Click the icon to see an image of a cystocele.

Antibiotics often eliminate lactobacilli, the protective bacteria, along with harmful bacteria. This causes an overgrowth of E. coli in the vagina. In one study, the risk for UTI increased during the 15 - 28 days that women were taking antibiotics. In fact, some research suggests that taking antibiotics for a urinary tract infection increases the risk for a subsequent infection.

Diabetes. Diabetes puts women at significantly higher risk for asymptomatic bacteriuria. The longer a woman has diabetes, the higher the risk. (Control of blood sugar has no effect on this condition.) The risk for UTI complications is also higher in people with diabetes. In fact, certain UTI-related abscesses are reported only in patients with diabetes. These patients are also at higher risk for fungal-related UTIs.

Kidney Problems. Nearly any kidney disorder increases the risk for complicated UTIs.

AIDS and Immunosuppressed Patients. Any infection is dangerous in people whose immune systems are damaged, and UTIs are no exception, particularly pyelonephritis.

Sickle-Cell Anemia. Patients with sickle-cell anemia are particularly susceptible to kidney damage from their disease, and UTIs put them at even greater risk.

Kidney Stones. In some cases, kidney stones can cause urinary tract obstruction that leads to infection, particularly pyelonephritis. Symptoms of severe urinary tract infection in people with a history of kidney stones may indicate obstruction, which is a serious condition.

Click the icon to see an image of kidney stones.

Zinc. High doses of zinc supplements may increase the risk for urinary tract infections and other urologic problems, according to a 2007 study. Researchers found that hospitalizations for urinary complications were far more common among patients who took high doses of zinc than those who did not take this mineral supplement. Patients in the study took 80 mg of zinc daily. In general, the recommended daily amount for zinc is 8 mg/day for women and 11 mg/day for men. Higher doses of zinc are sometimes prescribed for people with certain medical conditions, such as age-related macular degeneration (an eye disease). However, no one should take more than 40 mg/day of zinc without talking to a doctor.

Complications

Urinary discomfort and emotional distress are the primary concerns in most women with recurrent UTIs. One study reported significant impairment of a woman's quality of life during symptom periods, which affected social function, vitality, and emotional well-being.

Nearly all urinary tract infections are mild, treatable, and have no long-term consequences. Serious physical complications can occur in some cases, however, most often in hospitalized patients.

Obstruction and Widespread Infection. Very severe upper urinary tract infections may cause obstruction that results in widespread and even life-threatening infection. Patients who develop UTIs in the hospital are at higher risk for such infections than those outside the hospital. In one particularly dangerous form of kidney infection that obstructs the ureter, mortality rates exceed 40%. This specific condition should be suspected in people with diabetes who have severe UTIs.

Kidney Damage. In high-risk adults, recurrent UTIs may cause scarring in the kidneys, which over time can lead to hypertension and eventual kidney failure. People with UTIs who develop serious kidney disease from UTIs are likely to have other predisposing diseases or structural abnormalities. (Recurrent urinary tract infections, even in the kidney, almost never lead to progressive kidney damage in otherwise healthy women.)

Urge Incontinence. Recurrent UTIs may increase the risk for urge incontinence after menopause. (People with urge incontinence experience leakage and the need to urinate frequently.) [See In-Depth Report #50: Urinary incontinence.]

Kidney Stones. Kidney stones can be caused by urinary tract infections (as well as increase the risk for UTIs in the first place). Those known as struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of ammonia, which composes the crystals forming struvite stones. The stone-promoting bacterium is usually Proteus, but others include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci.

Urinary tract infections during pregnancy pose particular risks for both mother and child:

If asymptomatic bacteriuria is not detected and treated promptly in pregnant women, as many as 25% develop kidney infection (pyelonephritis), which in turn increases the risk for premature birth, infant mortality, and later chronic kidney disease.
Even if kidney infection does not develop, untreated UTIs occurring in the first and third trimester of pregnancy slightly increase the risk for mental retardation and developmental delay in the infant.
Certain strains of E. coli can increase the risk for complications during pregnancy, including miscarriage or premature delivery, even if pyelonephritis does not develop.
Infants of women who harbor Ureaplasma urealyticum also have an increased risk for respiratory infections.

Urinary tract infections are a major cause of hospitalization in children. Untreated, they can be very serious, particularly in children under 4 years old. Fortunately, with prompt treatment, childhood cases of upper urinary tract infections rarely cause any serious consequences.

Spread of Infection. Widespread infection is a major complication of a primary infection. Although laboratory tests in some infants with UTI may suggest the presence of meningitis (inflammation of the spinal column), in most of these UTI cases the outcome is good with treatment, and there appear to be no neurological symptoms afterward.

Kidney Scarring. Kidney scarring is the major concern in children who develop serious or recurrent UTIs. Scarring in young growing kidneys is much more serious than in the mature kidney. Over the years, it increases the risk for hypertension and kidney failure. In one study, evidence of scarring developed in 6% of children who had been hospitalized for a urinary tract infection. Children most at risk for this complication include:

Children with vesicoureteral reflux (VUR). (Carefully managed vesicoureteral reflux without scarring is not associated with serious complications.)
Abnormally structured urinary tracts
Recurrent kidney infections
A delay in treating an acute UTI

One encouraging study followed children with evidence of kidney scarring for 16 - 26 years. On average, their total kidney function was well preserved, although the scarred kidney had signs of lower function and patients with scarring in both kidneys were at higher risk for future problems. Earlier studies have shown poorer results, which suggests that outcomes are now improving with early detection and better follow-up.

Women with diabetes have more frequent and more severe UTIs than women without the disease. They also are more frequently hospitalized for kidney infections. In fact, the most serious, but rare, complications of urinary tract infections (pyelonephritis, widespread infections, abscesses, inflammation of the bladder wall) occur mostly in patients with diabetes.

Diagnosis

In younger women, UTI symptoms plus positive results on an over-the-counter dipstick test are often enough to make a diagnosis. Symptoms include frequent urination and vaginal burning, without other complications such as fever, chills, and pain in the kidney. In such cases, young women can usually receive treatment by calling a health professional (usually a nurse) who will prescribe antibiotics. A good response to antibiotic therapy usually eliminates the need for further tests.

This course is recommended only for nonpregnant women at low risk for recurrent infection who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be younger than 55 years old; other patients need to see a doctor for evaluation. Pregnant women should be screened for E. coli because of the risk of complications, including miscarriage, from certain strains of these bacteria.

About half of women with symptoms of a UTI actually have some other condition, such as irritation of the urethra, vaginitis, interstitial cystitis, or sexually transmitted diseases (STDs). Some of these problems may also accompany or lead to UTIs.

Vaginitis. Vaginitis is a common vaginal infection that can be caused by a fungus (candidiasis) or bacteria. Occasionally, the infection causes frequent urination, mimicking cystitis. The typical symptoms of vaginitis are itching and an abnormal discharge.

Sexually Transmitted Diseases. Women with painful urination whose urine does not exhibit signs of bacterial growth in culture may have a sexually transmitted disease. The most common culprit is the organism Chlamydia trachomatis. Other STDs that may be responsible include gonorrhea and genital herpes.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost predominantly in women. The average age of patients with IC is 40 years old, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Bladder Cancer. Bladder cancer is a rare cause of painful urination and is more common in men than in women.

Kidney Stones. The pain of kidney stones along with blood in the urine can resemble the symptoms of pyelonephritis. There are no bacteria present with kidney stones, however.

Thinning Urethral and Vaginal Walls. After menopause, the vaginal and urethral walls become dry and fragile, causing pain and irritation that can mimic a UTI.

Disorders in Children that Mimic UTIs. Problems that might cause painful urination in children include reactions to chemicals in bubble bath, diaper rashes, and infection from the pinworm parasite.

Prostate Conditions in Men. Prostate conditions, including prostatitis (inflammation of the prostate) and benign prostatic hyperplasia, can cause symptoms similar to urinary tract infections.

Click the icon to see an image of benign prostatic hypertrophy.

During an exam, the doctor should examine the pelvic and vaginal area in women. Men require a digital rectal examination to determine if prostate enlargement is present. The doctor will also examine the male genitals for signs of infection. In both men and women, the doctor should also check the abdomen and areas around the kidneys for swelling and tenderness.

With the exception of skin cancer, prostate cancer is the most common type of cancer among men in the United States. Early detection may result from a blood test called a PSA (prostate-specific antigen) or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness found during the exam might be a sign of prostate cancer.

Dipstick tests, available over the counter, are quite reliable in making a reasonable diagnosis of UTIs in women with symptoms. Dipstick tests may also be useful for identifying UTIs in children and infants. The test uses a chemical on a stick that when dipped in urine reacts to nitrites, substances produced by many of the bacteria that cause UTIs. A positive test (which indicates that an infection is present) often eliminates the need for urine cultures, a more expensive test used to detect bacteria. A negative dipstick test helps to avoid unnecessary antibiotics, which are contributing to the growing problem of antibiotic resistance. These tests are not entirely accurate, however, and studies report that they may miss up to 25% of actual UTIs. If a woman has persistent UTI symptoms, and the dipstick test is negative, she should check with her doctor to see if more accurate tests are needed.

A urine sample is needed for most extensive testing. In most cases, the doctor requests a clean-catch sample. There are also other methods for collecting urine, depending on the patient's condition.

Clean-Catch Sample. A clean-catch sample for UTI depends on a sample free of contaminants normally present at the opening of the urethra (white blood cells and bacteria unrelated to UTIs). To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the following steps are taken:

Patients must first wash their hands thoroughly, then wash the penis or vulva and surrounding area four times, with front-to-back strokes, using a new soapy sponge each time.
The patient must then begin urinating into the toilet and stop after a few drops.
The patient then positions the container to catch the middle portion of the stream. Ideally, this urine will contain only the bacteria and other evidence of the urinary tract infection.
The patient then urinates the remainder into the toilet.
The patient securely screws the container cap in place without touching the inside of the rim.

The sample is generally given to the doctor or sent to the laboratory for analysis.

Incontinence Pads. Testing and diagnosing UTIs in elderly patients who are incontinent is especially difficult, because of the similarities in symptoms. Researchers have found that pressing a dipstick into an incontinence pad is an effective way to screen for urinary tract infections in incontinent patients.

Collection with a Catheter. Some patients (small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample.

A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. A urinalysis offers a number of valuable clues for an accurate diagnosis:

Color and cloudiness of urine
Acidity
White blood cells (leukocytes). A high count of white cells in the urine is referred to as pyuria. (A leukocyte count over 10 per microliter is considered to indicate pyuria.) Pyuria is usually sufficient for a diagnosis of UTI in nonhospitalized patients if other standard symptoms (or just fever in small children) are also present.

Treatment can be started without the need for further tests if the following urinalysis results are present in patients with symptoms and signs of UTIs:

A high white cell count
Cloudy urine

A urine culture uses a urine specimen that is placed on an agar plate, then incubated in the laboratory for 24 - 48 hours. It is then examined for the presence of bacterial growth. Urinary tract infection is nearly always caused by a single species of bacteria, notably E. coli. Cultures have limitations, however. If a mix of different species is found, the test is considered contaminated and is redone. In addition, even if E. coli is identified, researchers are also looking for variants of these bacteria. Certain types may indicate a higher risk for a second infection, while others may even be protective against recurring infections. Furthermore, some organisms, such as Chlamydia, which is a sexually transmitted organism, may not be detected.

A urine culture is usually performed if the dipstick results are positive, but even if the results are negative, a culture may still be helpful under certain circumstances:

If urinalysis or dipstick is negative but the patient has UTI symptoms, particularly if the patient has recurring infections or is in a high-risk group.
If the doctor suspects complications.
In girls less than 2 years of age with a high fever of unknown origin that lasts 2 days or more.

Even if bacteria are present in the culture, a diagnosis of UTI depends on symptoms and gender:

The presence in a culture of at least 100,000 bacteria per milliliter of urine usually provides conclusive evidence of infection in women with symptoms.
A count of 100,000 bacteria per milliliter in a woman without symptoms indicates asymptomatic bacteriuria. The decision to treat depends on the woman's risk factors for complications.
In young women with symptoms of cystitis, a diagnosis of infection can reasonably be made with counts as low as 1,000 bacteria per milliliter.
Men are considered to have an infection with a count of only 1,000.

If doctors suspect that bacteria other than E. coli may be present, a Gram stain is used to help predict the species. This is a staining procedure used to make bacteria visible through a microscope. Many bacteria are categorized by the terms Gram-positive and Gram-negative.

Bacteria that turn pink from staining are called Gram-negative
Those that turn blue are called Gram-positive

Escherichia coli bacteria are Gram-negative and the most common cause of UTIs. If doctors suspect that bacteria other than E. coli are causing a UTI, a Gram stain is useful for identifying other species.

Because of the expense and the limited accuracy of imaging procedures, these techniques are used only for the following:

Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If a doctor suspects obstruction or an abscess
After a first urinary tract infection in children age 2 - 24 months to detect possible obstruction or vesicoureteral reflux. Tests include ultrasound and a voiding cystourethrogram and possibly scans. Some evidence suggests that ultrasound is probably not necessary, but at this time it is recommended by major medical groups.

Ultrasound. Ultrasound is a noninvasive, risk-free imaging test that can be used to screen for hydronephrosis (obstructions of the flow of urine), kidney stones that predispose to infection, and kidney abscesses. In men, ultrasound can detect enlargement or abscesses of the prostate and, when combined with x-rays, is an accurate method for detecting incomplete emptying of the bladder, a common cause of UTI in men over age 50. In children with urinary tract infections, it also can be used to detect vesicoureteral reflux, the defect of the valve-like mechanism between the ureter and bladder. Ultrasounds are not as accurate as voiding cystourethrograms.

Nuclear Scans. Imaging techniques called nuclear scans may be useful in certain complicated cases, such as detecting kidney scarring after pyelonephritis in children. They produce better images and expose the patient to far less radiation than x-rays. One such scan called dimercaptosuccinic acid (DMSA) scintigraphy uses injections of tiny amounts of radioactive tracers. A scanning machine (scintillation or gamma camera) is then used to detect pictures of the tracer in the kidney. This information is recorded on a computer screen or on film.

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Magnetic resonance imaging (MRI) and computed tomography (CT) scans are noninvasive advanced imaging techniques that are sometimes used when nuclear scans are inconclusive. A CT scan is useful for ruling out kidney stones or obstructions in women with recurrent UTIs.

X-Rays. Special x-rays can be used to screen for structural abnormalities, urethral narrowing, or incomplete emptying of the bladder, which can cause stagnation of urine and predispose to infection.

Voiding cystourethrogram is an x-ray of the bladder and urethra. To obtain a cystourethrogram, a dye, called contrast material, is injected through a catheter inserted into the urethra and passed through the bladder.
An intravenous pyelogram (IVP) is an x-ray of the kidney. For a pyelogram, the contrast matter is injected into a vein and eliminated by the kidneys. In both cases, the dye passes through the urinary tract and reveals any obstructions or abnormalities on x-ray images. Due to the possible risks to the fetus, x-rays are not performed on pregnant women.

Click the icon to see an image of a voiding cystourethrogram.

Click the icon to see an image of an intravenous pyelogram.

Cystoscopy. Cystoscopy is used to detect structural abnormalities, interstitial cystitis, or masses that might not show up on x-rays during an IVP. The patient is given a light anesthetic, and the bladder is filled with water. The procedure uses a cystoscope, a flexible, tube-like instrument that the urologist inserts through the urethra into the bladder.

Click the icon to see an image of cystoscopy.

No noninvasive test will differentiate between upper and lower urinary tract infections. This is a particular problem because of the high percentage of women whose cystitis symptoms mask infections that also exist in the upper tract.

Antibiotic Trial. The best current test for pyelonephritis is the short-term antibiotic therapy given for cystitis. If the infection returns within 2 weeks after treatment, upper urinary tract infection is usually present.

Blood Cultures. If symptoms are severe, blood cultures will be taken to determine if the infection is in the bloodstream and threatening other parts of the body.

Treatment

Although antibiotics should be used as a cure for most urinary tract infections, severe symptoms can persist for several days until treatment effectively eliminates the bacteria. A number of options are available for relieving symptoms until the antibiotics take action.

Important Note. All of the drugs discussed below treat only symptoms and are not cures. They should never be used to replace antibiotics.

Phenazopyridine (Pyridium, Uristat, Barodium, Eridium, AZO Standard) relieves pain and burning caused by the infection. It should not be taken for more than 2 days and should be discontinued when symptoms are relieved.

Side effects include headache and stomach distress. The drug turns urine a red or orange color, which can stain fabric and be difficult to remove. In rare cases, it can cause serious side effects, including shortness of breath, a bluish skin, a sudden reduction in urine output, shortness of breath, and confusion. In such cases, patients should immediately call the doctor.

Methenamine (Atrosept, Prosed, Urised) or flavoxate (Urispas) reduce bladder spasms, which may occur with some UTIs. These drugs can have severe side effects, however, that the patient should discuss with the doctor.

Medications

Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available, and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes). Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in humans and animal feed. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics that researchers investigated. As more bacteria have become resistant to the standard UTI treatment trimethoprim-sulfamethoxazole (TMP-SMX), more doctors have been prescribing quinolone antibiotics to treat UTIs. A 2006 study found that quinolones have now overtaken TMP-SMX as the most commonly prescribed antibiotic for UTIs. Experts are concerned that resistance may develop to these drugs as well.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar drugs. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by Gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed as:

First generation, including cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation, including cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation, including cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria.

Other Beta-Lactam Drugs. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The typical treatment is a 3-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A 1-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 - 10 days) work no better than the 3-day course and have a higher rate of side effects. TMP-SMX should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. TMP-SMX can interfere with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX exist in many parts of the United States. Still, even when regional rates approach 30%, cure rates with TMP-SMX reach 80 - 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) are now becoming as widely used as TMP-SMX. These drugs interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs
In patients who do not respond or who are allergic to TMP-SMX
In communities where there are high rates of bacteria resistant to TMP-SMX
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.

Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given 7 - 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within 1 - 2 weeks of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective 1-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.

UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional provides the patients with 3-day antibiotic regimens without even requiring an office urine test. This course is recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following antibiotics are commonly used for uncomplicated UTIs:

The standard regimen has traditionally been a 3-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). TMP-SMX combines an antibiotic with a sulfa drug. A single dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower than with the 3-day regimens.
Fluoroquinolone antibiotics, also called quinolones, have usually been a second choice. However, in geographic areas that have a high resistance to TMP-SMX, quinolones are now the first-line treatment for UTIs. Ciprofloxacin (Cipro) is the quinolone antibiotic most commonly prescribed. Quinolones are usually given over a 3–day period. Pregnant women should not take these drugs.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This drug must be given for longer than 3 days.
Fosfomycin (Monurol) is not as effective as other antibiotics but may be used during pregnancy. Resistance rates to this drug are very low.
Many other effective antibiotics are available, including amoxicillin (with or without clavulanate) and cephalosporins. Doxycycline is often effective but cannot be given to children or pregnant women.

After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, doctors generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within 3 weeks in about 10% of women. Relapse is treated similarly to a first infection, but the antibiotics are continued for at least 2 weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within 6 months or three or more over the course of a year. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use lifestyle measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self-treat recurrent UTIs without going to a doctor. In general, this requires the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the doctor for culturing to confirm the infection.

A doctor should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours
If there is a change in symptoms
If the patient suspects that she is pregnant
If the patient has more than four infections a year

Women who are not good candidates for self-treatment are those with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a 6-month period, a single preventive dose taken immediately after intercourse is very effective. Antibiotics for such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for 6 months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to 5 years of use.

Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and nonpregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria (Gram-positive organisms, including Enterococcus species and S. saprophyticus) that do not respond to standard regimens.

A urine culture may be obtained within 1 week of completion of therapy and again 4 weeks later.

Treating Moderate-to-Severe Kidney Infections. Patients with moderate-to-severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for 3 - 5 days or until symptoms are relieved and patients have not shown any signs of fever for 24 - 48 hours.

If fever and back pain persist after 72 hours of antibiotic administration, the doctor will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

The two approved treatments for interstitial cystitis are pentosan polysulfate (Elmiron), and dimethyl sulfoxide (DMSO). Patients generally prefer Elmiron because it can be taken by mouth. A DMSO solution is instilled into the bladder through a catheter. Elmiron is a type of blood thinner that helps to coat the bladder lining and prevent infections. It may take several months before having an effect on symptoms, but the benefits increase the longer the drug is used.

Doctors sometimes also prescribe other types of medications to help interstitial cystitis symptoms. These drugs include antihistamines, such as hydroxyzine (Atarax), and low doses of the tricyclic antidepressant amitriptyline (Elavil). Drugs that reduce bladder spasms (hyoscine, oxybutynin) are also sometimes used. Other treatments are being investigated, including hyperbaric oxygen therapy. This treatment involves having a patient breathe pure oxygen inside a sealed pressurized chamber.

Some doctors think that interstitial cystitis may be related to immune disorders. Researchers are investigating various drugs that block immune and inflammatory responses.

Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Pregnant women should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. They need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (3 - 5 days). For an uncomplicated UTI, pregnant women may need longer-term antibiotics (7 - 10 days).

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patients with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for 7 - 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a 7-day regimen of doxycycline. Some research suggests that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. However, once an infection spreads to the prostate gland it is harder to treat, so most doctors still prefer the longer regimen. Patients with urethritis should also be tested for an accompanying sexually transmitted disease such as gonorrhea.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). These drugs are usually taken by mouth in either liquid or pill form. Doctors sometimes give them as a shot or IV. Children usually respond to treatment within a few days. Antibiotic resistance to cephalosporin antibiotics such as cephalexin is increasing, and some doctors prefer to prescribe an aminoglycoside antibiotic. Gentamicin (Garamycin) is the aminoglycoside antibiotic that is most commonly used. It is given intravenously.

Vesicoureteral reflux (VUR) is a concern for children with UTIs. About a third of children with UTIs develop this condition, in which urine backs up into the kidneys. VUR can lead to kidney infection (pyelonephritis), which can cause kidney damage. Either long-term antibiotics or surgery are options to correct vesicoureteral reflux (VUR) and prevent infection. Many experts recommend surgery over antibiotics, especially due to concerns of antibiotic resistance. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. However, a 2006 study suggested that long-term antibiotics are not useful for preventing VUR. Furthermore, the study found that mild-to-moderate VUR does not increase the likelihood of UTIs or pyelonephritis.

Children with acute kidney infection are treated with oral cefixime (Suprax) or a short course (2 - 4 days) of an intravenous (IV) antibiotic (typically gentamicin, given in one daily dose). An oral antibiotic then follows the IV.

Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common, and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some doctors recommend replacing it every 2 weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including 3 glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.

Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.

Catheterization is accomplished by inserting a catheter (a hollow tube, often with an inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.

Other Treatments

The following are hygiene tips. Although there is no evidence that good hygiene makes a real difference in preventing UTIs, it is always a wise practice.

Clean the genital and urinary areas from front to back with soap and water after each bowel movement.
Keep the genital and anal areas clean before and after sex. Urinate before and after intercourse to empty the bladder and cleanse the urethra of bacteria.
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing both at least once a day. (Mild detergents are best for washing underwear.)
Take showers rather than baths.
Avoid bath oils, feminine hygiene sprays, douches, and powders. As a general rule, do not use any product containing perfumes or other possible allergens near the genital area. Douching in is never recommended. It may destroy the natural antiviral organisms normally present in the vagina, making women more susceptible to human papillomavirus (HPV), a risk factor for cervical cancer.
Choose sanitary napkins instead of tampons (which some doctors believe encourage infection). Napkins and tampons, in any case, should be changed after each urination.
Urinate frequently.

Appropriate hygiene and cleanliness of the genital area may help reduce the chances of introducing bacteria through the urethra. Females are especially vulnerable to this, because the urethra is in close proximity to the rectum. The genitals should be cleaned and wiped from front to back to reduce the chance of dragging E. coli bacteria from the rectal area to the urethra.

The following recommendations may reduce the risks from sexual activity:

In women using contraceptives, consider alternatives, particularly if exposed to spermicides from condoms or diaphragms. Discuss the best contraceptive choice with a doctor.
Avoid sex with multiple partners. This can cause many health problems, including sexually transmitted diseases and UTIs.

Postmenopausal women with recurrent UTIs may consider the use of an estrogen vaginal cream or estrogen-releasing vaginal ring (Estring). Estrogen may resist infection by increasing the number of lactobacilli, the microorganism that fights infection by lowering the vaginal pH levels and preventing E. coli from adhering to vaginal cells. Estrogen creams and estrogen-releasing rings may help reduce the risk of recurring urinary tract infections. Oral hormone replacement therapies that contain estrogen do not seem to provide the same benefit as the topical forms. Estrogen HRT carries many health risks, including an increased risk for breast cancer and heart disease. It is not clear if vaginal forms of estrogen are associated with these risks.

Many doctors believe that emptying the bladder frequently will help prevent bladder irritation and therefore recommend drinking plenty of water daily and urinating often.

Cranberries, blueberries, and lignonberry, a European relative of the cranberry, are three fruits that may have protective properties. Researchers are finding that red pigments in these closely related fruits called tannins (or proanthocyanadins) prevent E. coli bacteria from adhering to cells in the urinary tract, thereby inhibiting infection. Fructose, which is commonly used to sweeten fruit juices, may also interfere with bacterial adhesion.

Cranberry juice offers well-known protection against urinary tract infections. In one study, only 15% of elderly women who drank cranberry juice daily for 6 months experienced UTIs, compared with 28% of women who did not drink the juice. Its effects were stronger in helping the body rid itself of infections than in preventing them in the first place, but it showed benefits in both situations.

Studies suggest that for protection, it is necessary to drink at least one to two cups of 30% cranberry or lignonberry juice daily, or to take at least 300 - 400 mg in tablet form twice daily.

Important research has targeted probiotics (essentially friendly organisms), which may protect against infections in the genital and urinary tracts. They may have other health benefits as well. The best-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products (kefir). The probiotics bifidobacteria and GG lactobacilli may prove to be even more important. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Lactobacilli have the potential to help protect women from UTIs in a number of ways:

Maintain a low pH environment
Hinder E. coli growth
Produce hydrogen peroxide, which produces an environment hostile for bacteria

In a 2003 study, drinking fermented milk reduced the risk for UTIs. Not all studies show benefits from drinks containing lactobacilli, but more research is warranted.

Researchers are studying several different herbal treatments for urinary tract infections. Studies on these herbs have only been conducted on animals and cell samples -- not in humans:

Forskolin, an extract from the Indian coleus plant, may help flush out bacteria hiding in the lining of the bladder.
Green tea contains compounds that may help prevent inflammation in bladder cells.
St. John’s wort, a popular herbal remedy for depression, may help relieve pain associated with interstitial cystitis.

It is important to inform your doctor of any herbs, dietary supplements, or vitamins and minerals that you take or are considering taking. Some of these remedies may actually increase your chance of developing urinary tract infections. For example, high doses of zinc have been associated with increased risk of UTIs.

Biofeedback is a technique that provides visual and auditory clues in response to specific exercises. Some research indicates that biofeedback teaches children who are prone to UTIs to relax and control their pelvic muscles, resulting in fewer recurrences of infection.

Resources

http://kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Clearinghouse
www.urologyhealth.org -- American Urological Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.ichelp.com -- Interstitial Cystitis Association

References

Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30. Epub 2007 Apr 8.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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