Holistic Lifestyle Community Blog

Tremor: Diagnosis and Treatment

2012-02-27T15:40:00.001-08:00

A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements (oscillations or twitching) of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk and legs. Most tremors occur in the hands. In some people, tremor is a symptom of another neurological disorder. A very common kind of tremor is the chattering of teeth, usually induced by cold temperatures or by fear.

What Causes Tremor?

Tremor can be a symptom associated with disorders in those parts of the brain that control muscles throughout the body or in particular areas, such as the hands. Neurological disorders or conditions that can produce tremor include multiple sclerosis, stroke, traumatic brain injury, chronic kidney disease and a number of neurodegenerative diseases that damage or destroy parts of the brainstem or the cerebellum, Parkinson's disease being the one most often associated with tremor. Other causes include the use of drugs (such as amphetamines, caffeine, corticosteroids, SSRI), alcohol abuse or withdrawal, mercury poisoning; this is also in infants with phenylketonuria (PKU), overactive thyroid or liver failure. Tremors can be an indication of hypoglycemia, along with palpitations, sweating and anxiety. Tremor can also be caused from lack of sleep, vitamin deficiency, or increased stress. Deficiencies of magnesium and thiamine have also been known to cause tremor or shaking, which resolves when the deficiency is corrected. Some forms of tremor (i.e., familial) are inherited and run in families, while others have no known cause. Tremors can also be caused by some spider bites, for example, the redback spider of Australia.

Characteristics of tremor may include a rhythmic shaking in the hands, arms, head, legs or trunk; shaky voice; difficulty writing or drawing; or problems holding and controlling utensils, such as a fork. Some tremors may be triggered by or become exaggerated during times of stress or strong emotion, when the individual is physically exhausted, or during certain postures or movements.

Tremor may occur at any age but is most common in middle-age and older persons, typically around the age range of 52-61. It may be occasional, temporary, or occur intermittently. Tremor affects both men and women equally.

Etiologies

Tremor is most commonly classified by clinical features and cause or origin. Some of the better known forms of tremor, with their symptoms, include the following:

Cerebellar tremor (also known as intention tremor) is a slow, broad tremor of the extremities that occurs at the end of a purposeful movement, such as trying to press a button or touching a finger to the tip of one’s nose. Cerebellar tremor is caused by lesions in or damage to the cerebellum resulting from stroke, tumor, or disease such as multiple sclerosis or some inherited degenerative disorder. It can also result from chronic alcoholism or overuse of some medicines. In classic cerebellar tremor, a lesion on one side of the brain produces a tremor in that same side of the body that worsens with directed movement. Cerebellar damage can also produce a “wing-beating” type of tremor called rubral or Holmes’ tremor — a combination of rest, action, and postural tremors. The tremor is often most prominent when the affected person is active or is maintaining a particular posture. Cerebellar tremor may be accompanied by other manifestations of ataxia, including dysarthria (speech problems), nystagmus (rapid, involuntary rolling of the eyes), gait problems and postural tremor of the trunk and neck. Titubation is tremor of the head and is of cerebellar origin.
Dystonic tremor occurs in individuals of all ages who are affected by dystonia, a movement disorder in which sustained involuntary muscle contractions cause twisting and repetitive motions and/or painful and abnormal postures or positions. Dystonic tremor may affect any muscle in the body and is seen most often when the patient is in a certain position or moves a certain way. The pattern of dystonic tremor may differ from essential tremor. Dystonic tremors occur irregularly and often can be relieved by complete rest. Touching the affected body part or muscle may reduce tremor severity (a geste antagoniste). The tremor may be the initial sign of dystonia localized to a particular part of the body.
Essential tremor (sometimes called benign essential tremor) is the most common of the more than 20 types of tremor. Although the tremor may be mild and nonprogressive in some people, in others, the tremor is slowly progressive, starting on one side of the body but affecting both sides within 3 years. The hands are most often affected but the head, voice, tongue, legs, and trunk may also be involved. Head tremor may be seen as a “yes-yes” or “no-no” motion. Essential tremor may be accompanied by mild gait disturbance. Tremor frequency may decrease as the person ages, but the severity may increase, affecting the person’s ability to perform certain tasks or activities of daily living. Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremors and/or increase their severity. Onset is most common after age 40, although symptoms can appear at any age. It may occur in more than one family member. Children of a parent who has essential tremor have a 50% chance of inheriting the condition. Essential tremor is not associated with any known pathology. For more information on essential tremor see my Blog "Essential Tremor".
Orthostatic tremor is characterized by fast (>12 Hz) rhythmic muscle contractions that occur in the legs and trunk immediately after standing. Cramps are felt in the thighs and legs and the patient may shake uncontrollably when asked to stand in one spot. No other clinical signs or symptoms are present and the shaking ceases when the patient sits or is lifted off the ground. The high frequency of the tremor often makes the tremor look like rippling of leg muscles while standing. Orthostatic tremor may also occur in patients who have essential tremor, and there might be an overlap between these categories of tremor.
Parkinsonian tremor is caused by damage to structures within the brain that control movement. This resting tremor, which can occur as an isolated symptom or be seen in other disorders, is often a precursor to Parkinson's disease (more than 25% of patients with Parkinson’s disease have an associated action tremor). The tremor, which is classically seen as a "pill-rolling" action of the hands that may also affect the chin, lips, legs, and trunk, can be markedly increased by stress or emotions. Onset of parkinsonian tremor is generally after age 60. Movement starts in one limb or on one side of the body and usually progresses to include the other side.
Physiologic tremor occurs in every normal individual and has no clinical significance. It is rarely visible and may be heightened by strong emotion (such as anxiety or fear), physical exhaustion, hypoglycemia, hyperthyroidism, heavy metal poisoning, stimulants, alcohol withdrawal or fever. It can be seen in all voluntary muscle groups and can be detected by extending the arms and placing a piece of paper on top of the hands. Enhanced physiologic tremor is a strengthening of physiologic tremor to more visible levels. It is generally not caused by a neurological disease but by reaction to certain drugs, alcohol withdrawal, or medical conditions including an overactive thyroid and hypoglycemia. It is usually reversible once the cause is corrected.
Psychogenic tremor (also called hysterical tremor) can occur at rest or during postural or kinetic movement. The characteristics of this kind of tremor may vary but generally include sudden onset and remission, increased incidence with stress, change in tremor direction and/or body part affected, and greatly decreased or disappearing tremor activity when the patient is distracted. Many patients with psychogenic tremor have a conversion disorder or another psychiatric disease.
Rubral tremor is characterized by coarse slow tremor which is present at rest, at posture and with intention. This tremor is associated with conditions which affect the red nucleus in the midbrain, classically unusual strokes.

Tremor can result from other conditions as well, such as:

Alcoholism, excessive alcohol consumption, or alcohol withdrawal can kill certain nerve cells, resulting a tremor known as asterixis. Conversely, small amounts of alcohol may help to decrease familial and essential tremor, but the mechanism behind this is unknown. Alcohol potentiates gabaergic transmission and might act at the level of the inferior olive.
Tremor in peripheral neuropathy may occur when the nerves that supply the body’s muscles are traumatized by injury, disease, abnormality in the central nervous system, or as the result of systemic illnesses. Peripheral neuropathy can affect the whole body or certain areas, such as the hands, and may be progressive. Resulting sensory loss may be seen as a tremor or ataxia (inability to coordinate voluntary muscle movement) of the affected limbs and problems with gait and balance. Clinical characteristics may be similar to those seen in patients with essential tremor.
Tobacco withdrawal symptoms also include tremor.
Geiger's rigors are tremors resulting from prolonged exposure to Kolac positive women (women who have been diagnosed with bacterial vaginosis).

Most of the symptoms can also occur randomly when panicked, while being ultimately unrelated.

Diagnosis

During a physical exam a doctor can determine whether the tremor occurs primarily during action or at rest. The doctor will also check for tremor symmetry, any sensory loss, weakness or muscle atrophy, or decreased reflexes. A detailed family history may indicate if the tremor is inherited. Blood or urine tests can detect thyroid malfunction, other metabolic causes, and abnormal levels of certain chemicals that can cause tremor. These tests may also help to identify contributing causes, such as drug interaction, chronic alcoholism, or another condition or disease. Diagnostic imaging using CT or MRI imaging may help determine if the tremor is the result of a structural defect or degeneration of the brain.

Diagram "Human Nervous System"

The doctor will perform a neurological examination to assess nerve function and motor and sensory skills. The tests are designed to determine any functional limitations, such as difficulty with handwriting or the ability to hold a utensil or cup. The patient may be asked to place a finger on the tip of her or his nose, draw a spiral, or perform other tasks or exercises. The doctor may order an electromyogram to diagnose muscle or nerve problems. This test measures involuntary muscle activity and muscle response to nerve stimulation. The selection of the sensors used is important. In addition to studies of muscle activity, tremor can be assessed with accuracy using accelerometers.

Categories

The degree of tremor should be assessed in four positions. The tremor can then be classified by which position most accentuates the tremor:

Position Name Description

At rest (resting tremors): Tremors that are worse at rest include Parkinsonian syndromes and essential tremor if severe. This includes drug-induced tremors from blockers of dopamine receptors such as haloperidol® and other antipsychotic drugs.
During contraction (e.g. a tight fist while the arm is resting and supported): Tremors that are worse during supported contraction include essential tremor and also cerebellar and exaggerated physiologic tremors such as a hyperadrenergic state or hyperthyroidism. Drugs such as adrenergics, anticholinergics, and xanthines can exaggerate physiologic tremor.
During posture (e.g. with the arms elevated against gravity such as in a 'bird-wing' position): Tremors that are worse with posture against gravity include essential tremor and exaggerated physiologic tremors.
During intention (e.g. finger to nose test) Tremors that are worse during intention, (e.g. as the patient's finger approaches a target), including cerebellar disorders. The terminology of "intention" is currently less used, to the profit of "kinetic".

Treatment

There is no cure for most tremors. The appropriate treatment depends on accurate diagnosis of the cause. Some tremors respond to treatment of the underlying condition. For example, in some cases of psychogenic tremor, treating the patient’s underlying psychological problem may cause the tremor to disappear.

Medications

Medications remain the basis of therapy in many cases. Symptomatic drug therapy is available for several forms of tremor:

Parkinsonian tremor drug treatment involves L-DOPA® and/or dopamine-like drugs such as pergolide®, bromocriptine® and ropinirole®. These can be dangerous, however, as they may cause symptoms such as tardive dyskinesia, akathisia, clonus, and in rare instances tardive (late developing) psychosis. Other drugs used to lessen parkinsonian tremor include amantadine® and anticholinergic drugs like benzatropine®.
Essential tremor may be treated with beta blockers (such as propranolol® and nadolol®) or primidone®, an anticonvulsant.
Cerebellar tremor typically does not respond to medical treatment.
Rubral tremor patients may receive some relief using L-DOPA® or anticholinergic drugs. Surgery may be helpful.
Dystonic tremor may respond to diazepam®, anticholinergic drugs, and intramuscular injections of botulinum toxin®. Botulinum toxin® is also prescribed to treat voice and head tremors and several movement disorders.
Primary orthostatic tremor sometimes is treated with a combination of diazepam® and primidone®. Gabapentin® provides a relief in some cases.
Enhanced physiologic tremor is usually reversible once the cause is corrected. If symptomatic treatment is needed, beta blockers can be used.

Lifestyle

Eliminating tremor “triggers” such as caffeine and other stimulants from the diet is often recommended. Essential tremor may benefit from slight doses of ethanol (do not use the ethanol treatment if you are a recovering alcoholic), but the potential negative consequences of regular ethanol intake need to be taken into account.

Physical therapy may help to reduce tremor and improve coordination and muscle control for some patients. A physical therapist will evaluate the patient for tremor positioning, muscle control, muscle strength, and functional skills. Teaching the patient to brace the affected limb during the tremor or to hold an affected arm close to the body is sometimes useful in gaining motion control. Coordination and balancing exercises may help some patients. Some therapists recommend the use of weights, splints, other adaptive equipment, and special plates and utensils for eating.

Surgery

Surgical intervention such as thalamotomy and deep brain stimulation may ease certain tremors. These surgeries are usually performed only when the tremor is severe and does not respond to drugs. Response can be excellent.

Thalamotomy, involving the creation of lesions in the brain region called the thalamus, is quite effective in treating patients with essential, cerebellar, or parkinsonian tremor. This in-hospital procedure is performed under local anesthesia, with the patient awake. After the patient’s head is secured in a metal frame, the surgeon maps the patient’s brain to locate the thalamus. A small hole is drilled through the skull and a temperature-controlled electrode is inserted into the thalamus. A low-frequency current is passed through the electrode to activate the tremor and to confirm proper placement. Once the site has been confirmed, the electrode is heated to create a temporary lesion. Testing is done to examine speech, language, coordination, and tremor activation, if any. If no problems occur, the probe is again heated to create a 3-mm permanent lesion. The probe, when cooled to body temperature, is withdrawn and the skull hole is covered. The lesion causes the tremor to permanently disappear without disrupting sensory or motor control.

Deep Brain Stimulation (DBS) uses implantable electrodes to send high-frequency electrical signals to the thalamus. The electrodes are implanted as described above. The patient uses a hand-held magnet to turn on and turn off a pulse generator that is surgically implanted under the skin. The electrical stimulation temporarily disables the tremor and can be “reversed,” if necessary, by turning off the implanted electrode. Batteries in the generator last about 5 years and can be replaced surgically. DBS is currently used to treat parkinsonian tremor and essential tremor. It is also applied successfully for other rare causes of tremor.

The most common side effects of tremor surgery include dysarthria (problems with motor control of speech), temporary or permanent cognitive impairment (including visual and learning difficulties), and problems with balance.

Biomechanical Loading

As well as medication, rehabilitation programmes and surgical interventions, the application of biomechanical loading on tremor movement has been shown to be a technique that is able to suppress the effects of tremor on the human body. It has been established in the literature that most of the different types of tremor respond to biomechanical loading. In particular, it has been clinically tested that the increase of damping and/or inertia in the upper limb leads to a reduction of the tremorous motion. Biomechanical loading relies on an external device that either passively or actively acts mechanically in parallel to the upper limb to counteract tremor movement. This phenomenon gives rise to the possibility of an orthotic management of tremor.

Starting from this principle, the development of upper-limb non-invasive ambulatory robotic exoskeletons is presented as a promising solution for patients who cannot benefit from medication to suppress the tremor. In this area robotic exoskeletons have emerged, in the form of orthoses, to provide motor assistance and functional compensation to disabled people. An orthosis is a wearable device that acts in parallel to the affected limb. In the case of tremor management, the orthosis must apply a damping or inertial load to a selected set of limb articulations.

Recently, some studies demonstrated that exoskeletons could achieve a consistent 40% of tremor power reduction for all users, being able to attain a reduction ratio in the order of 80% tremor power in specific joints of users with severe tremor. In addition, the users reported that the exoskeleton did not affect their voluntary motion. These results indicate the feasibility of tremor suppression through biomechanical loading.

The main drawbacks of this mechanical management of tremor are:

the resulting bulky solutions,
the inefficiency in transmitting loads from the exoskeleton to the human musculo-skeletal system, and
technological limitations in terms of actuator technologies.

In this regard, current trends in this field are focused on the evaluation of the concept of biomechanical loading of tremor through selective Functional Electrical Stimulation (FES) based on a (Brain-to-Computer Interaction) BCI-driven detection of involuntary (tremor) motor activity.

External Links

Tremor Action Network (USA)
National Tremor Foundation (UK)
NINDS Tremor Information Page (National Institute of Neurological Disorders and Stroke)

References

Allan H. Goroll; Albert G. Mulley (1 January 2009). Primary care medicine: office evaluation and management of the adult patient. Lippincott Williams & Wilkins. p. 1178. ISBN 978-0-7817-7513-7. http://books.google.com/books?id=bIZvJPcSEXMC&pg=PA1178 retrieved 30 May 2011.
Grimaldi G, Manto M. "Neurological tremor: sensors, signal processing and emerging applications". Sensors. 2010;10:1399–1422.
Jankovic J, Fahn S. Physiologic and pathologic tremors. Diags, mechanism, and management. Ann Intern Med. 1980;93:460–465.
Rocon E, Belda-Lois JM, Ruiz AF, Manto M, Moreno JC, Pons JL. "Design and Validation of a Rehabilitation Robotic Exoskeleton for Tremor Assessment and Suppression." IEEE Transactions on Neural Systems and Rehabilitation Engineering. 2007;15(3):367–378.

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Essential Tremor

2012-02-27T15:28:00.001-08:00

Essential tremor (ET) is a slowly progressive neurological disorder of which the most recognizable feature is a tremor of the arms or hands that is apparent during voluntary movements such as eating and writing.  This type of tremor is often referred to as kinetic tremor. The tremor may also occur in the head (neck), jaw and voice as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in selected patients. Women are more likely to develop the head tremor than are men.

Other types of tremor may also occur, including postural tremor of the outstretched arms, intentional tremor of the arms and rest tremor in the arms.  Some patients may have unsteadiness and problems with gait and balance that are above and beyond that due to normal aging.  In addition to these motor problems, a variety of non-motor features have recently been linked with essential tremor. These include anxiety and depressive symptoms as well as cognitive difficulty.

Recent studies have demonstrated that late-onset essential tremor (onset > age 65) may be associated with an increased risk of developing dementia.  Essential tremor is one of the most common neurological diseases, with a prevalence of approximately 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, 80s, and 90s.  Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders.

Essential tremor was also previously known as "benign essential tremor", but the adjective "benign" has been removed in recognition of the sometimes disabling nature of the disorder. Although essential tremor is often mild, patients with severe tremor have difficulty performing many of their routine activities of daily living.

Signs and Symptoms

Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that is present only when the affected muscle is exerting effort (in other words, it is not present at rest). Any sort of physical or mental stress will tend to make the tremor worse, often creating the false impression that the tremor is of psychosomatic origin.

Tremor intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold, caffeine, lithium salts, some antidepressants or other factors. It is typical for the tremor to worsen in "performance-type" situations, such as when writing a cheque for payment at a store or giving a presentation.

ET-related tremors do not occur during sleep, but patients sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness.

In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty to do small precise tasks such as threading a needle. Even simple tasks like cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's ability to perform tasks of daily living, including feeding, dressing, and activities of personal hygiene.

People with ET can sometimes have problems with word finding and can't articulate themselves effectively even with preparation. A person with ET may become shy, withdrawn, pessimistic, anxious and also have difficulties concentrating. It is common for those with ET to be embarrassed by the condition even though it is out of their control.

ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases.

Though it is not directly a result of the condition, a high number of people with ET develop a dependence on alcohol. This is due to the fact alcohol helps alleviate the tremor, making things like social gatherings much more enjoyable for the sufferer. However the next day it is common to suffer from a "rebound tremor" where the tremor is more noticeable than normal. This leads to many people "chasing the tail" and leading to a problem far worse than the symptoms listed.

Cause

The underlying etiology is not clear but many cases seem to be familial.  It has been estimated that approximately one-half of the cases is due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. As of yet, no genes have been identified but genetic linkage has been established with several chromosomal regions.  A number of environmental factors, including toxins, are also under active investigation and these may play a role in disease etiology.  In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits.  Recent postmortem studies have demonstrated the presence of degenerative changes in the ET brain, with these changes including Purkinje cell axonal swellings and Purkinje cell loss in the majority of cases and brainstem Lewy bodies in the remainder. These studies suggest that the disease is both heterogeneous and degenerative. In other words, ET might be a family of degenerative diseases rather than a single disease.

However, emerging research based on brain autopsies of fifty deceased ET patients (as of Dec. 2009), showed clear degenerative and pathological abnormalities, including "messy" neurofilaments which can impede nerve impulses. Research by Dr. Elan Louis and colleagues revealed that 80% of autopsied brains also exhibited changes within the cerebellum particularly to neurons that produce GABA, a major inhibitory neurotransmitter. Further analysis showed elevated levels of two neurotoxins, lead and harmane, a heterocyclic amine. Heterocyclic amines (HCA) are chemicals found in some foods. Harmane has been detected in coffee and cigarettes but is especially prevalent in meats that have been barbecued or exposed to high heat. Another research indicates there is a strong link between essential tremor in males and the amount of meat consumed, but the exact mechanism is yet unknown.

Changes in the cerebelleum could also be mediated by alcohol consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity.  The impairment could lead to the abnormal cerebellar circuitry seen in essential tremor and suggests that alcohol may also work as an exacerbating agent in the pathology of this disease. Chronic ethanol consumption results in a loss of Purkinje cell synapses. However, these synapses are regained following a period of recovery that includes gradual weaning of off ethanol. Continued consumption of ethanol inhibits the recovery of synapses.  This impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor. Chronic alcohol abuse has also been linked to other movement disorders such as myoclonus, ataxia, and dyskinesia.

Diagnosis

Usually the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor).  Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the patient's head to shake), tongue, and legs. A resting tremor of the hands is sometimes present. ET does sometimes occur in combination with other neurological disorders such as dystonia. In addition, there may be a link between ET and Parkinson's disease, with one study showing ET patients having an approximately 4 times greater likelihood of developing Parkinson's disease.

Treatment

There is no cure for essential tremor. Many of the treatments available are to lower the severity of the condition. These may include:

Medication: The two most recommended medications are: the beta-blockers propranolol® and the antiepileptic primidone®. Self medication with small amounts of alcohol has been shown to give short term relief from tremor, although this form of self-medication is not recommended due an increased risk of alcohol dependence or abuse. However other alcohol groups such as 1-octanol are being researched to provide relief from essential tremor without providing the intoxication or toxicity that ethanol does. Gabapentin® may be helpful in the treatment of essential tremor. A trial of the benzodiazepine-anticonvulsant Clonazepam® (Klonopin®, Rivotril®) was found not to be an effective treatment; however, it is still recommended in some cases. Topiramate® has also been cited as a possible pharmaceutical treatment.
Other Medication: Memantine® (Namenda®), a drug that has been approved by the Food and Drug Administration (FDA) for its use as an Alzheimer's disease medication, has been researched for its potential ameliorative effects on ET http://clinicaltrials.gov/ct2/show/NCT00439699. Memantine® is not as potent as ethanol at decreasing tremor intensity or locomotion. However, memantine® exhibits neuroprotective effects. Memantine® treatment results in a significantly higher reduction in caspase-3 positive neurons.
Surgical treatments (which are generally reserved for the most severe cases) include thalamotomy and deep brain stimulation.
Minor cases of ET can be treated with physical therapy and development of the muscles in the sections of the body that are severe in their shaking.

Mild cases of ET which are not affecting activities of daily life may not require any treatment. Use of wrist weights and avoiding triggers such as caffeine may be helpful.

Support Groups

The International Essential Tremor Foundation (IETF) provides information, services and support to individuals and families affected by essential tremor (ET). The organization encourages and promotes research in an effort to determine the causes, treatment and ultimately the cure for ET. The IETF is a worldwide organization dedicated to meeting the needs of those whose daily lives are challenged by ET. IETF, an international non-profit 501(c)(3) organization that derives its support entirely from its membership and the general public, was founded in 1988 and is guided by a board of directors and a medical advisory council. The organization's membership consists of patients, physicians, educators, parents, relatives and volunteers who provide education, community services and funding to help support tremor research.

The National Tremor Foundation (NTF), founded in 1992, is a British friendly organisation based in Essex, England, an affiliate of the International Tremor Foundation, which was founded in 1988. The organisation's primary work is production of a quarterly informational newsletter. The NTF also maintains a list of ITF medical advisors, and facilitates the formation of self-help groups. NTF was granted charitable status in 1994.

Research

Harmaline-induced Tremor

Harmaline is a widely used model of essential tremor (ET) in rodents.  Harmaline is thought to act primarily on neurons in the inferior olive (IO). Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally.  Additionally, when harmaline is administered to lesioned IOs, little to no tremors are observed, reinforcing harmalines’ specificity for inferior olive connections.  The treatment of harmaline results in higher levels of caspase-3 immunoreactivity in Purkinje, granule and inferior olive cells, suggestive of harmaline-mediated apoptosis.  Harmaline also increases the concentration of glutamate in cerebellar nuclei which disrupts normal NMDA-mediated down-regulation of glutamate release.  Together, these interferences likely give rise to essential-tremor like behavior that is likely a result of diseregulation of glutamatergic circuitry within the cerebellum.

Ethanol Mechanisms

Ethanol is effective at decreasing tremor intensity and locomotion.  Ethanol-mediated effects are not observed on tremor frequency and peak location.  Additionally, ethanol is able to reduce caspase-3 induced apoptosis though not without an increased loss of neurons in the cerebellum and olivary nucleus.  Ethanol has been shown to decrease levels of glutamate in the cerebellar nuclei which had been pre-treated with harmaline.  Furthermore, ethanol directly reduces hyperactivity of the climbing fiber-Purknije cell synapse by acting on glutamatergic receptors.  Ethanol may reduce tremor by dampening the overexcitation of glutamatergic pathways involving deep cerebellar nuclei which may also reduce levels of caspase-3 induced apoptosis.

Octanol Mechanism

Different alcohols exert similar ameliorative effects on harmaline-induced tremors, though to different degrees. Different isomers of octanol vary in efficacy when it comes to antagonizing harmaline-mediated tremors. These effects are likely mediated in the inferior olive, specifically at low-threshold calcium channels (LTCC) which have been shown to modulate the rhythmic firing of cells in this area.  Octanol, specifically by binding to LTCCs of IOs, behaves in an antagonistic fashion on the spike discharges from Purkinje cells. The most potent isomers: (+)2-octanol, (-)2-octanol and 4-octanol, followed by 4-octanol, and lastly, 1-octanol.  Both the magnitude and duration of the tremor are dependent on the octanol isomer. Differences in solubility does not appear to account for the disparity between isomers.

Genetically-induced Tremor

Genetic animal models of essential tremor utilize GABAA receptor α1 -/- mice because of the major role GABA plays in inhibiting motor activity. Moreover, GABAA receptor α1 -/- mice produce essential-like tremors and motor impairment as seen in ET patients.

Ethanol mechanisms

Alcohol is implicated as a therapeutic agent for GABAA receptor α1 -/- mice because of its interaction with Purkinje cells which mediate their actions via GABA transmission.  GABAA receptor α1 -/- mice respond positively to ethanol treatment. Ethanol reduces tremor activity in GABAA receptor α1 -/- mice in a dose dependent manner. An optimum dose of 2.5 g/kg of ethanol completely suppresses tremors in GABAA receptor α1 -/- mice.  Purkinje cells in these knockout mice also exhibit a lack of GABAergic inhibitory postsynaptic potentials in response to both exogenous and endogenous GABA. The loss of GABAergic inhibition in purkinje cells likely underlies the pathological tremors observed.  These ameliorative effects are thought to involve inhibition of glutamatergic transmission, though the numerous targets of ethanol make it difficult to determine the exact underlying mechanism.

External Links

International Essential Tremor Foundation (USA)
Tremor Action Network (USA)
National Tremor Foundation (UK)
Association APTES (France)
Leonid L. Rubchinsky et al. (2007) Tremor. Scholarpedia 2(10):1379
Brain Autopsies Reveal Abnormalities
Essential Tremor Centralized Brain Repository
Essential Tremor Info
NINDS Tremor Information Page - National Institute of Neurological Disorders and Stroke

References

Benito-Leon J, Louis ED. Clinical update: Diagnosis and treatment of essential tremor. The Lancet 2007;369:1152-1153.
Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC. Clinical expression of essential tremor: Effects of gender and age. Mov Disord 1997;12:969-972.
Louis ED, Ford B, Frucht S. Factors associated with increased risk of head tremor in essential tremor: A community-based study in northern manhattan. Mov Disord 2003;18:432-436.
Louis ED. Clinical Practice: Essential tremor. N Engl J Med 2001;345:887-891.
Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. November 2001;124(Pt 11):2278-2286.
Singer C, Sanchez-Ramos J, Weiner WJ. Gait abnormality in essential tremor. Mov Disord. March 1994;9(2):193-196.
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Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Botanical Dietary Supplements: FAQs

2012-02-27T11:53:00.000-08:00

What is a botanical?

A botanical is a plant or plant part valued for its medicinal or therapeutic properties, flavor, and/or scent. Herbs are a subset of botanicals. Products made from botanicals that are used to maintain or improve health may be called herbal products, herbal remedies, botanical products, botanical medicines or phytomedicines.

In naming botanicals, botanists use a Latin name made up of the genus and species of the plant. Under this system the botanical black cohosh is known as Actaea racemosa L., where the initial "L" stands for Linneaus, who first described the type of plant specimen. Initials often do not appear on most dietary supplement product labels used by consumers.

Botanical dietary supplements can be purchased at an apothecary, local supermarket, or natural grocer such as Whole Foods®, Vitamin Cottage®, etc.

"Apothecary"

Can botanicals be dietary supplements?

To be classified as a dietary supplement, a botanical must meet the definition given below. Many botanical preparations meet the definition.

As defined by Congress in the Dietary Supplement Health and Education Act, which became law in 1994, a dietary supplement is a product (other than tobacco) that:

is intended to supplement the diet;
contains one or more dietary ingredients (including vitamins; minerals; herbs or other botanicals; amino acids; and other substances) or their constituents;
is intended to be taken by mouth as a pill, capsule, tablet, or liquid; and
is labeled on the front panel as being a "dietary supplement".

How are botanicals commonly sold and prepared?

Botanicals are sold in many forms: as fresh or dried products; liquid or solid extracts; tablets, capsules, powders; tea bags; and other forms. For example, fresh ginger root is often found in the produce section of food stores; dried ginger root is sold packaged in tea bags, capsules, or tablets; and liquid preparations made from ginger root are also sold. A particular group of chemicals or a single chemical may be isolated from a botanical and sold as a dietary supplement, usually in tablet or capsule form. An example is phytoestrogens from soy products.

Note: Keep in mind that the majority of adverse [side] effects tend to occur when a medicinal plant's chemical constituent is separated from the whole plant. This is often the case with the manufacturers of modern-day pharmaceuticals and their multitudinous side effects. To save on expenses (it is extremely expensive to fully research the literally hundreds of individual chemical constituents contained in just one medicinal botanical) and to "get the drug out there" pharmaceutical manufacturers will often isolate (separate) one active chemical from a botanical and then combine it with other man-made chemicals to produce their drug of choice. It is important to understand that the whole plant helps to negate or offset any side effects that may occur from any one particular chemical constituent found in the plant. It must be remembered that while a particular botanical’s chemical constituent may be considered dangerous or even toxic when isolated and concentrated, as part of the combination of complex elements in the whole botanical it is usually quite safe.

Common preparations include teas, decoctions, tinctures, and extracts:

A tea, also known as an infusion, is made by adding boiling water to fresh or dried botanicals and steeping them. The tea may be drunk either hot or cold.
Some roots, bark, and berries require more forceful treatment to extract their desired ingredients. They are simmered in boiling water for longer periods than teas, making a decoction, which also may be drunk hot or cold.
A tincture is made by soaking a botanical in a solution of alcohol and water. Tinctures are sold as liquids and are used for concentrating and preserving a botanical. They are made in different strengths that are expressed as botanical-to-extract ratios (i.e., ratios of the weight of the dried botanical to the volume or weight of the finished product).
An extract is made by soaking the botanical in a liquid that removes specific types of chemicals. The liquid can be used as is or evaporated to make a dry extract for use in capsules or tablets.

Are botanical dietary supplements standardized?

Standardization is a process that manufacturers may use to ensure batch-to-batch consistency of their products. In some cases, standardization involves identifying specific chemicals (also known as markers) that can be used to manufacture a consistent product. The standardization process can also provide a measure of quality control.

Dietary supplements are not required to be standardized in the United States. In fact, no legal or regulatory definition exists for standardization in the United States as it applies to botanical dietary supplements. Because of this, the term "standardization" may mean many different things. Some manufacturers use the term standardization incorrectly to refer to uniform manufacturing practices; following a recipe is not sufficient for a product to be called standardized. Therefore, the presence of the word "standardized" on a supplement label does not necessarily indicate product quality.

Ideally, the chemical markers chosen for standardization would also be the constituents that are responsible for a botanical's effect in the body. In this way, each lot of the product would have a consistent health effect. However, the components responsible for the effects of most botanicals have not been identified or clearly defined. For example, the sennosides in the botanical senna are known to be responsible for the laxative effect of the plant, but many compounds may be responsible for valerian's relaxing effect.

Are botanical dietary supplements safe?

Many people believe that products labeled "natural" are safe and good for them. This is not necessarily true because the safety of a botanical depends on many things, such as its chemical makeup, how it works in the body, how it is prepared, the dose used, other medications (i.e., prescription, over the counter, other herbals, etc.) that the consumer is currently taking, and the consumer's overall health.

Modern-day medicines were and still are derived from some of nature's botanicals, and the therapeutic action of those botanicals range from mild to powerful (potent). A botanical with mild action may have subtle effects. Chamomile and peppermint, both mild botanicals, are usually taken as teas to aid digestion and are generally considered safe for self-administration. Some mild botanicals may have to be taken for weeks or months before their full effects are achieved. For example, valerian may be effective as a sleep aid after 14 days of use but it is rarely effective after just one dose. In contrast a powerful botanical produces a fast result. Kava Kava, as one example, is reported to have an immediate and powerful action affecting anxiety and muscle relaxation. Another example of a very powerful or potent botanical is Foxglove Digitalis purpurea, a common biennial garden plant that contains digitoxin, digoxin, and other cardiac glycosides. These are naturally occurring chemical constituents in the plant that affect the heart. Digitalis® is currently in use today as a potent heart (cardiac) drug.

The dose and form of a botanical preparation also play important roles in its safety. Teas, tinctures, and extracts have different strengths. The same amount of a botanical may be contained in a cup of tea, a few teaspoons of tincture, or an even smaller quantity of an extract. Also, different preparations vary in the relative amounts and concentrations of chemical removed from the whole botanical. For example, peppermint tea is generally considered safe to drink but peppermint essential oil is much more concentrated and can be toxic if used incorrectly or ingested. It is important to follow the manufacturer's suggested directions for using a botanical and not exceed the recommended dose without the advice of a qualified health care provider.

Does a label indicate the quality of a botanical dietary supplement product?

It is difficult to determine the quality of a botanical dietary supplement product from its label. The degree of quality control depends on the manufacturer, the supplier, and others in the production process.

In 2007, the Food and Drug Administration (FDA) issued Good Manufacturing Practices (GMPs) for dietary supplements, a set of requirements and expectations by which dietary supplements must be manufactured, prepared, and stored to ensure quality. Manufacturers are now expected to guarantee the identity, purity, strength, and composition of their dietary supplements. For example, the GMPs aim to prevent the inclusion of the wrong ingredients, the addition of too much or too little of a dietary ingredient, the possibility of contamination (by pesticides, heavy metals such as lead, bacteria, insects and/or larvae, rodent droppings, etc.), and the improper packaging and labeling of a product.

What methods are used to evaluate the health benefits and safety of a botanical dietary supplement?

Like other dietary supplements, botanicals are not required by federal law to be tested for safety and effectiveness before they are marketed, so the amount of scientific evidence available for various botanical ingredients varies widely. Some botanicals have been evaluated in scientific studies. For example, research shows that St. John's wort may be useful for short-term treatment of occasional bouts of mild to moderate depression (Caution! do not use St. John's wort or any other botanical with antidepressant properties for severe depression - bipolar/manic depressive conditions). Other botanical dietary supplements need more study to determine their value.

Scientists can use several approaches to evaluate botanical dietary supplements for their potential health benefits and risks. They may investigate history of use, conduct laboratory studies using cell or tissue cultures, and experiment with animals. Studies on people (e.g., individual case reports, observational studies, and clinical trials) provide the most direct evidence of a botanical supplement's effects on health and patterns of use.

What are some additional sources of information on botanical dietary supplements?

Medical libraries are one source of information about botanical dietary supplements. Others include web-based resources such as PubMed, the National Institutes of Health (NIH), the Food and Drug Administration (FDA), and others. For general information about utilizing herbs for health and beauty refer to the popular book Let's Get Natural with Herbs (or see the top of this Blog) by Debra J. Rayburn.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Sleep Apnea

2012-02-26T15:13:00.001-08:00

Sleep apnea (or sleep apnoea in British English; English pronunciation: AP·ne·ah) is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low breathing event is called a hypopnea. Sleep apnea is diagnosed with an overnight sleep test called a polysomnogram, or sleep study.

There are three forms of sleep apnea: central (CSA), obstructive (OSA), and complex or mixed sleep apnea (i.e., a combination of central and obstructive) constituting 0.4%, 84% and 15% of cases respectively. In CSA, breathing is interrupted by a lack of respiratory effort; in OSA, breathing is interrupted by a physical block to airflow despite respiratory effort, and snoring is common.

Regardless of type, an individual with sleep apnea is rarely aware of having difficulty breathing, even upon awakening. Sleep apnea is recognized as a problem by others witnessing the individual during episodes or is suspected because of its effects on the body (sequelae). Symptoms may be present for years (or even decades) without identification, during which time the sufferer may become conditioned to the daytime sleepiness and fatigue associated with significant levels of sleep disturbance.

Signs and Symptoms

Sleep apnea affects not only adults but some children as well.  As stated by El-Ad, "patients complain about excessive daytime sleepiness (EDS) and impaired alertness".  In other words, common effects of sleep apnea include daytime fatigue, a slower reaction time, and vision problems.  Moreover, patients are examined using “standard test batteries” in order to further identify parts of the brain that are affected by sleep apnea.  Tests have shown that certain parts of the brain cause different effects. The “executive functioning” part of the brain affects the way the patient plans and initiates tasks.  Second, the part of the brain that deals with attention causes difficulty in paying attention, working effectively and processing information when in a waking state.  Thirdly, the part of the brain that uses memory and learning is also affected.  Due to the disruption in daytime cognitive state, behavioral effects are also present.  This includes moodiness, belligerence, as well as a decrease in attentiveness and drive.  These effects become very difficult to deal with, thus the development of depression may transpire.  Finally, because there are many factors that could lead to some of the effects previously listed, some patients are not aware that they suffer from sleep apnea and are either misdiagnosed, or just ignore the symptoms altogether.

Diagnosis

The diagnosis of sleep apnea is based on the conjoint evaluation of clinical symptoms (e.g. excessive daytime sleepiness and fatigue) and of the results of a formal sleep study (polysomnography, or reduced channels home based test). The latter aims at establishing an "objective" diagnosis indicator linked to the quantity of apneic events per hour of sleep (Apnea Hypopnea Index(AHI), or Respiratory Disturbance Index (RDI)), associated to a formal threshold, above which a patient is considered as suffering from sleep apnea, and the severity of their sleep apnea can then be quantified.

Nevertheless, due to the number and variability in the actual symptoms and nature of apneic events (e.g., hypopnea vs apnea, central vs obstructive), the variability of patients' physiologies, and the intrinsic imperfections of the experimental setups and methods, this field is opened to debate.  Within this context, the definition of an apneic event depends on several factors (e.g. patient's age) and account for this variability through a multi-criteria decision rule described in several, sometimes conflicting, guidelines.  One example of a commonly adopted definition of an apnea (for an adult) includes a minimum 10 second interval between breaths, with either a neurological arousal (a 3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2) or a blood oxygen desaturation of 3-4% or greater, or both arousal and desaturation.

Oximetry

Oximetry, which may be performed overnight in a patient's home, is an easier alternative to polysomnography (formal sleep study). In one study, normal overnight oximetry was very sensitive and so if normal, sleep apnea was unlikely.  In addition, home oximetry may be equally effective in guiding prescription for automatically self-adjusting continuous positive airway pressure.

Obstructive Sleep Apnea (OSA)

Obstructive sleep apnea is the most common category of sleep-disordered breathing. The muscle tone of the body ordinarily relaxes during sleep, and at the level of the throat the human airway is composed of collapsible walls of soft tissue which can obstruct breathing during sleep. Mild occasional sleep apnea, such as many people experience during an upper respiratory infection, may not be important, but chronic severe obstructive sleep apnea requires treatment to prevent low blood oxygen (hypoxemia), sleep deprivation, and other complications.

"Sleep Apnea" Illustration© Habib M'henni

Individuals with low muscle tone and soft tissue around the airway (e.g., because of obesity) and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. The elderly are more likely to have OSA than young people. Men are more likely to suffer sleep apnea than women and children are, though it is not uncommon in the last two population groups.

The risk of OSA rises with increasing body weight, active smoking and age. In addition, patients with diabetes or "borderline" diabetes have up to three times the risk of having OSA. Common symptoms include loud snoring, restless sleep, and sleepiness during the daytime. Diagnostic tests include home oximetry or polysomnography in a sleep clinic.

Some treatments involve lifestyle changes, such as avoiding alcohol or muscle relaxants, losing weight, and quitting smoking. Many people benefit from sleeping at a 30-degree elevation of the upper body or higher, as if in a recliner. Doing so helps prevent the gravitational collapse of the airway. Lateral positions (sleeping on a side), as opposed to supine positions (sleeping on the back), are also recommended as a treatment for sleep apnea, largely because the gravitational component is smaller in the lateral position. Some people benefit from various kinds of oral appliances to keep the airway open during sleep. Continuous positive airway pressure (CPAP) is the most effective treatment for obstructive sleep apnea. There are also surgical procedures to remove and tighten tissue and widen the airway.

As already mentioned, snoring is a common finding in people with this syndrome. Snoring is the turbulent sound of air moving through the back of the mouth, nose, and throat. Although not everyone who snores is experiencing difficulty breathing, snoring in combination with other conditions such as overweight and obesity has been found to be highly predictive of OSA risk. The loudness of the snoring is not indicative of the severity of obstruction, however. If the upper airways are tremendously obstructed, there may not be enough air movement to make much sound. Even the loudest snoring does not mean that an individual has sleep apnea syndrome. The sign that is most suggestive of sleep apneas occurs when snoring stops.

Other indicators include (but are not limited to):

Hypersomnolence,
Obesity BMI >30,
Large neck circumference (16 in (410 mm) in women, 17 in (430 mm) in men),
Enlarged tonsils and large tongue volume,
Micrognathia (a condition where the jaw is undersized. Common in infants it is usually self-correcting during growth),
Morning headaches,
Irritability/mood-swings/depression,
Learning and/or memory difficulties, and
Sexual dysfunction.

The term "sleep-disordered breathing" is commonly used in the U.S. to describe the full range of breathing problems during sleep in which not enough air reaches the lungs (hypopnea and apnea). Sleep-disordered breathing is associated with an increased risk of cardiovascular disease, stroke, high blood pressure, arrhythmias, diabetes, and sleep deprived driving accidents.  When high blood pressure is caused by OSA, it is distinctive in that, unlike most cases of high blood pressure (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping.  Stroke is associated with obstructive sleep apnea.

In the June 27, 2008, edition of the journal Neuroscience Letters, researchers revealed that people with OSA show tissue loss in brain regions that help store memory, thus linking OSA with memory loss.  Using magnetic resonance imaging (MRI), the scientists discovered that sleep apnea patients' mammillary bodies were nearly 20 percent smaller, particularly on the left side. One of the key investigators hypothesized that repeated drops in oxygen lead to the brain injury.

Central Sleep Apnea

In pure central sleep apnea or Cheyne-Stokes respiration, the brain's respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide, and the neurological feedback mechanism that monitors them, do not react quickly enough to maintain an even respiratory rate, with the entire system cycling between apnea and hyperpnea, even during wakefulness. The sleeper stops breathing and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no struggling. After the episode of apnea, breathing may be faster (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases and absorb more oxygen.

While sleeping, a normal individual is "at rest" as far as cardiovascular workload is concerned. Breathing is regular in a healthy person during sleep, and oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant. The respiratory drive is so strong that even conscious efforts to hold one's breath do not overcome it. Any sudden drop in oxygen or excess of carbon dioxide (even if tiny) strongly stimulates the brain's respiratory centers to breathe.

In central sleep apnea, the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. If the pause in breathing is long enough, the percentage of oxygen in the circulation will drop to a lower than normal level (hypoxaemia) and the concentration of carbon dioxide will build to a higher than normal level (hypercapnia). In turn, these conditions of hypoxia and hypercapnia will trigger additional effects on the body. Brain cells need constant oxygen to live, and if the level of blood oxygen goes low enough for long enough, the consequences of brain damage and even death will occur. Fortunately, central sleep apnea is more often a chronic condition that causes much milder effects than sudden death. The exact effects of the condition will depend on how severe the apnea is and on the individual characteristics of the person having the apnea. Several examples are discussed below.

In any person, hypoxia and hypercapnia have certain common effects on the body. The heart rate will increase, unless there are such severe co-existing problems with the heart muscle itself or the autonomic nervous system that makes this compensatory increase impossible. The more translucent areas of the body will show a bluish or dusky cast from cyanosis, which is the change in hue that occurs owing to lack of oxygen in the blood ("turning blue"). Overdoses of drugs that are respiratory depressants (such as heroin, and other opiates) kill by damping the activity of the brain's respiratory control centers. In central sleep apnea, the effects of sleep alone can remove the brain's mandate for the body to breathe.

Normal Respiratory Drive:

After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the blood stream (called chemoreceptors) send nerve impulses to the brain, which then signals reflex opening of the larynx (so that the opening between the vocal cords enlarges) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it.

Physiologic Effects of Central Apnea:

During central apneas, the central respiratory drive is absent, and the brain does not respond to changing blood levels of the respiratory gases. No breath is taken despite the normal signals to inhale. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures. At worst, central sleep apnea may cause sudden death. Short of death, drops in blood oxygen may trigger seizures, even in the absence of epilepsy. In people with epilepsy, the hypoxia caused by apnea may trigger seizures that had previously been well controlled by medications. In other words, a seizure disorder may become unstable in the presence of sleep apnea. In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction). Longstanding recurrent episodes of apnea, over months and years, may cause an increase in carbon dioxide levels that can change the pH of the blood enough to cause a metabolic acidosis. It also causes a slight struggling that the person is not aware of. If not recognized by anyone awake it may lead to death, or any other problems. This is similar to an asthma attack but not quite the same as it gives you a feeling as if you are being strangled by someone.

Mixed Apnea and Complex Sleep Apnea

Some people with sleep apnea have a combination of both types. When obstructive sleep apnea syndrome is severe and longstanding, episodes of central apnea sometimes develop. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown but is most commonly related to acid-base and CO2 feedback malfunctions stemming from heart failure. There is a constellation of diseases and symptoms relating to body mass, cardiovascular, respiratory, and occasionally, neurological dysfunction that have a synergistic effect in sleep-disordered breathing. In some cases, a side effect from the lack of sleep is a mild case of Excessive Daytime Sleepiness (EDS) where the subject has had minimal sleep and this extreme fatigue over time takes its toll on the subject. The presence of central sleep apnea without an obstructive component is a common result of chronic opiate use (or abuse) owing to the characteristic respiratory depression caused by large doses of narcotics.

Complex sleep apnea has recently been described by researchers as a novel presentation of sleep apnea. Patients with complex sleep apnea exhibit OSA, but upon application of positive airway pressure the patient exhibits persistent central sleep apnea. This central apnea is most commonly noted while on CPAP therapy after the obstructive component has been eliminated. This has long been seen in sleep laboratories and has historically been managed either by CPAP or BiLevel therapy. Adaptive servo-ventilation (ASV) modes of therapy have been introduced to attempt to manage this complex sleep apnea. Studies have demonstrated marginally superior performance of the adaptive servo ventilators in treating Cheyne-Stokes breathing; however, no longitudinal studies have yet been published, nor have any results been generated that suggest any differential outcomes versus standard CPAP therapy. At the AARC 2006 in Las Vegas, NV, researchers reported successful treatment of hundreds of patients on ASV therapy.

An important finding by Dernaika et al. suggests that transient central apnea produced during CPAP titration (the so-called "complex sleep apnea") is "…transient and self-limited".  The central apneas may in fact be secondary to sleep fragmentation during the titration process.

Research is ongoing, however, at the Harvard Medical School, including adding dead space to positive airway pressure for treatment of complex sleep-disordered breathing.

Treatment

Treatment often starts with behavioral therapy. For mild cases of sleep apnea, physicians often recommend sleeping on one's side, which can prevent the tongue and palate from falling backwards in the throat and blocking the airway. Many patients are told to avoid alcohol, sleeping pills, and other sedatives, which can relax throat muscles, contributing to the collapse of the airway at night.

For moderate to severe sleep apnea, the most common treatment is the use of a continuous positive airway pressure (CPAP) or Automatic Positive Airway Pressure (APAP) device, which 'splints' the patient's airway open during sleep by means of a flow of pressurized air into the throat. The patient typically wears a plastic facial mask, which is connected by a flexible tube to a small bedside CPAP machine. The CPAP machine generates the required air pressure to keep the patient's airways open during sleep. Advanced models may warm or humidify the air and monitor the patient's breathing to ensure proper treatment. Although CPAP therapy is extremely effective in reducing apneas and less expensive than other treatments, some patients find it extremely uncomfortable. Many patients refuse to continue the therapy or fail to use their CPAP machines on a nightly basis.

CPAP Full Face Mask (oxygen tube attaches to front apparatus)

In addition to CPAP, dentists specializing in sleep disorders can prescribe Oral Appliance Therapy (OAT). The oral appliance is a custom-made mouthpiece that shifts the lower jaw forward, opening up the airway. OAT is usually successful in patients with mild to moderate obstructive sleep apnea. OAT is a relatively new treatment option for sleep apnea in the United States, but it is much more common in Canada and Europe.

Several surgical procedures are used to treat sleep apnea, although they are normally a second line of treatment for those who reject CPAP treatment or are not helped by it. Surgical treatment for obstructive sleep apnea needs to be individualized in order to address all anatomical areas of obstruction. Often, correction of the nasal passages needs to be performed in addition to correction of the oropharynx passage. Septoplasty and turbinate surgery may improve the nasal airway. Tonsillectomy and uvulopalatopharyngoplasty (UPPP or UP3) are available to address pharyngeal obstruction. Base-of-tongue advancement by means of advancing the genial tubercle of the mandible may help with the lower pharynx. A myriad of other techniques is available, including hyoid bone myotomy and suspension and various radiofrequency technologies.

"Surgery on the mouth and throat" Illustration© Habib M'henni

Other surgery options may attempt to shrink or stiffen excess tissue in the mouth or throat; procedures done at either a doctor's office or a hospital. Small shots or other treatments, sometimes in a series, are used for shrinkage, while the insertion of a small piece of stiff plastic is used in the case of surgery whose goal is to stiffen tissues.

The Pillar Procedure is a minimally invasive treatment for snoring and obstructive sleep apnea. This procedure was FDA indicated in 2004. During this procedure, three to six+ dacron (the material used in permanent sutures) strips are inserted into the soft palate, using a modified syringe and local anesthetic. While the procedure was initially approved for the insertion of three "pillars" into the soft palate, it was found that there was a significant dosage response to more pillars, with appropriate candidates. After this brief and virtually painless outpatient operation, which usually lasts no more than 30 minutes, the soft palate is more rigid and snoring and sleep apnea can be reduced. This procedure addresses one of the most common causes of snoring and sleep apnea - vibration or collapse of the soft palate (the soft part of the roof of the mouth). If there are other factors contributing to snoring or sleep apnea, such as the nasal airway or an enlarged tongue, it will likely need to be combined with other treatments to be more effective.

Possibly owing to changes in pulmonary oxygen stores, sleeping on one's side (as opposed to on one's back) has been found to be helpful for central sleep apnea with Cheyne-Stokes respiration (CSA-CSR).

Medications like Acetazolamide® lower blood pH and encourage respiration. Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.

Surgery

CPAP is the most consistently safe and effective treatment for obstructive sleep apnea, but it is not a cure. People are less likely to use it in the long term.  The Stanford Center for Excellence in Sleep Disorders Medicine achieved a 95% cure rate of sleep apnea patients by surgery.  Maxillomandibular advancement (MMA) is considered the most effective surgery for sleep apnea patients, because it increases the posterior airway space (PAS).  The main benefit of the operation is that the oxygen saturation in the arterial blood increases.  In a study published in 2008, 93.3% of surgery patients achieved an adequate quality of life based on the Functional Outcomes of Sleep Questionnaire (FOSQ).  Surgery led to a significant increase in general productivity, social outcome, activity level, vigilance, intimacy and sex.  Overall risks of MMA surgery are low: The Stanford University Sleep Disorders Center found 4 failures in a series of 177 patients, or about one out of 44 patients.  However, health professionals are often unsure as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impeding surgery; or significant craniofacial abnormalities which hinder device use.

Several inpatient and outpatient procedures use sedation. Many drugs and agents used during surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards. In an individual with either central, obstructive or mixed sleep apnea, these low doses may be enough to cause life-threatening irregularities in breathing or collapses in a patient’s airways.  Use of analgesics and sedatives in these patients postoperatively should therefore be minimized or avoided.

Surgery on the mouth and throat, as well as dental surgery and procedures, can result in postoperative swelling of the lining of the mouth and other areas that affect the airway. Even when the surgical procedure is designed to improve the airway, such as tonsillectomy and adenoidectomy or tongue reduction, swelling may negate some of the effects in the immediate postoperative period. Once the swelling resolves and the palate becomes tightened by postoperative scarring, however, the full benefit of the surgery may be noticed.

Sleep apnea patients undergoing any medical treatment must make sure his or her doctor and/or anesthetist are informed about their condition. Alternate and emergency procedures may be necessary to maintain the airway of sleep apnea patients.  If an individual suspects he or she may have sleep apnea, communication with their doctor about possible preprocedure screening may be in order.

Alternative Treatments

A 2005 study in the British Medical Journal found that learning and practicing the didgeridoo helped reduce snoring and sleep apnea as well as daytime sleepiness. This appears to work by strengthening muscles in the upper airway, thus reducing their tendency to collapse during sleep. Other studies have also suggested that strengthening the muscles around the upper airway may combat sleep apnea. A 2009 study published in the American Journal of Respiratory and Clinical Care Medicine found that patients who practiced a series of tongue and throat exercises for 30 minutes a day showed a marked decline in sleep apnea symptoms after three months. Patients experienced an average of 39% fewer apnea episodes after successfully completing the treatments.

Epidemiology

The Wisconsin Sleep Cohort Study estimated in 1993 that roughly one in every 15 Americans were affected by at least moderate sleep apnea.  It also estimated that in middle-age as many as 9% of women and 24% of men were affected, undiagnosed and untreated. The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S. the average untreated sleep apnea patient's annual health care costs $1,336 more than an individual without sleep apnea. This may cause $3.4 billion/year in additional medical costs. Whether medical cost savings occur with treatment of sleep apnea remains to be determined.

History

The clinical picture of this condition has long been recognized as a character trait, without an understanding of the disease process. The term "Pickwickian syndrome" that is sometimes used for the syndrome was coined by the famous early 20th century physician, William Osler, who must have been a reader of Charles Dickens. The description of Joe, "the fat boy" in Dickens's novel The Pickwick Papers, is an accurate clinical picture of an adult with obstructive sleep apnea syndrome. The early reports of obstructive sleep apnea in the medical literature described individuals who were very severely affected, often presenting with severe hypoxemia, hypercapnia and congestive heart failure.

The management of obstructive sleep apnea was revolutionized with the introduction of continuous positive airway pressure (CPAP), first described in 1981 by Colin Sullivan and associates in Sydney, Australia.  The first models were bulky and noisy, but the design was rapidly improved and by the late 1980s CPAP was widely adopted. The availability of an effective treatment stimulated an aggressive search for affected individuals and led to the establishment of hundreds of specialized clinics dedicated to the diagnosis and treatment of sleep disorders. Though many types of sleep problems are recognized, the vast majority of patients attending these centers have sleep-disordered breathing.

External Links

American Sleep Apnea Association

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Stem Cell Therapies/Treatments

2012-02-25T15:01:00.001-08:00

Stem cell treatments are a type of intervention strategy that introduces new cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities, offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

A number of stem cell therapies exist, but most are at experimental stages or costly, with the notable exception of bone marrow transplantation. Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac disease, cardiac failure, muscle damage, neurological disorders, and many others. Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.

Current Treatments

For over 30 years, bone marrow, and more recently, umbilical cord blood stem cells, have been used to treat cancer patients with conditions such as leukemia and lymphoma.  During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.

Potential Treatments

Brain Damage

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Interestingly, in pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.  Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness. Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.

Cancer

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs; although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.  Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer.  Research on treating Lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

Spinal Cord Injury

A team of Korean researchers reported on November 25, 2003, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and that following the procedure, she could walk on her own, without difficulty. The patient had not been able to stand up for roughly 19 years. For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.

According to the October 7, 2005 issue of The Week, University of California, Irvine researchers transplanted multipotent human fetal-derived neural stem cells into paralyzed mice, resulting in locomotor improvements four months later. The observed recovery was associated with differentiation of transplanted cells into new neurons and oligodendrocytes- the latter of which forms the myelin sheath around axons of the central nervous system, thus insulating neural impulses and facilitating communication with the brain.

In January 2005, researchers at the University of Wisconsin–Madison differentiated human blastocyst stem cells into neural stem cells, then into pre-mature motor neurons, and finally into spinal motor neurons, the cell type that, in the human body, transmits messages from the brain to the spinal cord and subsequently mediates motor function in the periphery. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher Su-Chun Zhang described the process as "teaching the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time".

Transformation of blastocyst stem cells into motor neurons had eluded researchers for decades. While Zhang's findings were a significant contribution to the field, the ability of transplanted neural cells to establish communication with neighboring cells remains unclear. Accordingly, studies using chicken embryos as a model organism can be an effective proof-of-concept experiment. If functional, the new cells could be used to treat diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.

Heart Damage

Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe, effective, and equally efficient in treating old and recent infarcts.  Adult stem cell therapy for treating heart disease was commercially available in at least five continents at the last count (2007).

[Video] The Board of Governors Heart Stem Cell Center - Cedars Sinai Medical Center

Possible mechanisms of recovery include:

Generation of heart muscle cells
Stimulation of growth of new blood vessels to repopulate damaged heart tissue
Secretion of growth factors
Assistance via some other mechanism

It may be possible to have adult bone marrow cells differentiate into heart muscle cells.

Haematopoiesis (blood cell formation)

The specificity of the human immune cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are called hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.  Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

Baldness

Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through an activation of the stem cells progenitor cells. This treatment is expected to work by activating already existing stem cells on the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair. Most recently, Dr. Aeron Potter of the University of California has claimed that stem cell therapy led to a significant and visible improvement in follicular hair growth. Results from his experiments are under review by the journal Science (journal).

Missing Teeth

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients. In theory, stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to grow within two months.  It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.

Deafness

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.

Blindness and Vision Impairment

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable". When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.  The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.

In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.

In January 2012, The Lancet published a paper by Dr. Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.

Amyotrophic Lateral Sclerosis (Lou Gehrig's disease)

Stem cells have resulted in significant locomotor improvements in rats with an Amyotrophic lateral sclerosis-like disease. In a rodent model that closely mimics the human form of ALS, animals were injected with a virus to kill the spinal cord motor nerves which mediate movement. Animals subsequently received stem cells in the spinal cord. Transplanted cells migrated to the sites of injury, contributed to regeneration of the ablated nerve cells, and restored locomotor function.

Graft vs. host disease and Crohn's disease

Phase III clinical trials which ended in second-quarter 2008 were conducted by Osiris Therapeutics using their in-development product Prochymal®, derived from adult bone marrow. The target disorders of this therapeutic are graft-versus-host disease and Crohn's disease.

Neural and Behavioral Birth Defects

A team of researchers led by Prof. Joseph Yanai were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate.  This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as shown both in behavioral tests and objective brain chemistry tests. Behavioral tests and learning scores of the treated mice showed rapid improvement after treatment, providing results that rivaled non-treated mice. On the molecular level, brain chemistry of the treated animals was also restored to normal. Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.

The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published in January 2008 in the leading journal, Molecular Psychiatry. Scientists are now developing procedures to administer the neural stem cells in the least invasive way possible - probably via blood vessels, making therapy practical and clinically feasible. Researchers also plan to work on developing methods to take cells from the patient's own body, turn them into stem cells, and then transplant them back into the patient's blood via the blood stream. Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.

Diabetes

Diabetes patients lose the function of insulin-producing beta cells within the pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:

Transplanted cells should proliferate
Transplanted cells should differentiate in a site-specific manner
Transplanted cells should survive in the recipient (prevention of transplant rejection)
Transplanted cells should integrate within the targeted tissue
Transplanted cells should integrate into the host circuitry and restore function

Orthopaedics

Clinical case reports in the treatment of orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.  The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3 to 4 year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation. Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.

Wound Healing

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.  A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.  Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.

Infertility

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis. Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.  It could potentially treat azoospermia.

Clinical Trials

On January 23, 2009, the US Food and Drug Administration (FDA) gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was dicontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions”. As of mid 2010 hundreds of phase III clinical trials involving stem cells have been registered.

Stem Cell use in Animals

Veterinary Applications: Potential contributions to veterinary medicine

Research currently conducted on horses, dogs, and cats can benefit the development of stem-cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.  While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.  Companion animals can serve as clinically relevant models that closely mimic human disease.

Development of Regenerative Treatment Models

Veterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons.  Because mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments (as well as muscle, fat, and possibly other tissues), they have been the main type of stem cells studied in the treatment of diseases affecting these tissues.  Mesenchymal stem cells are primarily derived from adipose tissue or bone marrow. Since an elevated immune response following cell transplantation may result in rejection of exogenous cells (except in the case of cells derived from a very closely genetically related individual), mesenchymal stem cells are often derived from the patient prior to injection in a process known as autologous transplantation. Surgical repair of bone fractures in dogs and sheep has demonstrated that engraftment of mesenchymal stem cells derived from a genetically different donor within the same species, termed allogeneic transplantation, does not elicit an immunological response in the recipient animal and can mediate regeneration of bone tissue in major bony fractures and defects.

Stem cells can speed up bone repair in fractures/defects that would normally require extensive grafting, suggesting that mesenchymal stem cell use may provide a useful alternative to conventional grafting techniques.  Treating tendon and ligament injuries in horses using stem cells, whether derived from adipose tissue or bone-marrow, has support in the veterinary literature.  While further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures, stem cells are thought to mediate repair via five primary mechanisms:

Providing an antiinflammatory effect,
Homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells, that are necessary for tissue growth,
Supporting tissue remodeling over scar formation,
Inhibiting apoptosis, and
Differentiating into bone, cartilage, tendon and ligament tissue.

Significance of Stem Cell Microenvironments

The microenvironment into which stem cells are transplanted significantly alters the capacity of engrafted cells for recovery and repair. The microenviroment provides growth factors and other chemical signals that guide appropriate differentiation of transplanted cell populations and direct transplanted cells to sites of trauma or disease. Repair and recovery can then be mediated via three primary mechanisms:

Formation and/or recruitment of new blood cells to the damaged region;
Prevention of programed cell death or apoptosis; and
Suppression of inflammation.

To further enrich blood supply to the damaged areas, and consequently promote tissue regeneration, platelet-rich plasma could be used in conjunction with stem cell transplantation.  The efficacy of some stem cell populations may also be affected by the method of delivery; for instance, to regenerate bone, stem cells are often introduced in a scaffold where they produce the minerals necessary for generation of functional bone.

Sources of Autologous (patient-derived) Stem Cells

Autologous stem cells intended for regenerative therapy are generally isolated either from the patient's bone marrow or from adipose tissue. The number of stem cells transplanted into damaged tissue may alter efficacy of treatment. Accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells.  Although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells.  While it is thought that bone-marrow derived stem cells are preferred for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation.

Currently Available Treatments for Horses and Dogs Suffering from Orthopaedic Conditions

Autologous or allogeneic stem cells are currently used as an adjunctive therapy in the surgical repair of some types of fractures in dogs and horses.  Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the United States and since 2006 in the United Kingdom. Autologous stem-cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005. Over 3,000 privately-owned horses and dogs have been treated with autologous adipose-derived stem cells. The efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage.  The efficacy of using stem cells, whether adipose-derived or bone-marrow derived, for treating tendon and ligament injuries in horses has support in the veterinary literature.

Developments in Stem Cell Treatments in Veterinary Internal Medicine

Currently, research is being conducted to develop stem cell treatments for:

Horses suffering from COPD, neurologic disease, and laminitis; and
Dogs and cats suffering from heart disease, liver disease, kidney disease, neurologic disease, and immune-mediated disorder

Stem Cell Controversy

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral or religious objections.

Stem Cell Treatments Around the World

China

Stem cell research and treatment is currently being practiced at a clinical level in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem cell therapy for conditions beyond those approved of in Western countries such as the United States, United Kingdom, and Australia. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures, despite the overwhelmingly positive anecdotal results.

Stem cell therapies provided in China utilize a variety of cell types including umbilical cord stem cells and olfactory ensheathing cells. The stem cells are then expanded in centralized blood banks before being used in stem cell treatments. State-funded companies based in the Shenzhen Hi-Tech Industrial Zone treat the symptoms of numerous disorders with adult stem cell therapy. Hospitals throughout eastern China provide numerous therapies to patients in coordination with the stem cell providers. These companies' therapies are currently focused on the treatment of neurodegenerative and cardiovascular disorders. The most radical successes of Chinese adult stem cell therapy have been in treating the brain. These therapies administer stem cells directly to the brain to promote greater motor and brain function in patients with Cerebral Palsy, Alzheimer's disease, and brain injuries. However, retrospective studies have shown that Chinese use of fetal-derived brain tissue in spinal cord injured human subjects were not as promising as once thought: the phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, were unknown. As well, perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings.  Furthermore, the extent of regulatory policy in the use of stem cell therapies in China is unclear.  In the absence of a valid clinical trials protocol, and more regulatory oversight, Western regulatory agencies advise patients and physicians to be cautious when selecting Chinese stem cell therapeutic centers.

Mexico

Stem cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. This permit allows the use of stem cell types beyond those approved of in Western countries such as the United States or Europe. Stem cell therapies provided in Mexico utilize patient Adipose, Bone Marrow, or Donor Placenta sources.

South Korea

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection. This study, however, was eventually discredited as the primary researcher, Dr. Woo Suk Hwang, admitted to using cells obtained from his research staff.  In Dec 2005, claims were put forward that his research had been manipulated to wrongfully indicate positive results. Later that month, these claims were confirmed by an academic panel.

Ukraine

Today, the Ukraine is permitted to perform clinical trials of stem cell treatments (Order of the MH of Ukraine № 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

External Links

Stem Cell Institute - Adult Stem Cell Therapy Clinics
Centre for Regenerative Medicine - Institute for Stem Cell Research
Research Programs at Universities and Institutions [Stem Cell information]
National Institutes of Health (NIH)- Stem Cell information page

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Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Acetyl-L-Carnitine (ALCAR)

2012-02-23T11:33:00.001-08:00

Acetyl-L-carnitine (ALCAR), is an acetylated form of L-carnitine. It is a dietary supplement and naturally occurs in plants and animals.

From time to time, a well-known and valued supplement is reformulated to provide significant new benefits. Such is the case with L-carnitine. Propionyl-L-carnitine* is a form that until recently was restricted to medical uses. Under the name GPLC®, it is now available more readily as the patented compound, glycine propionyl-L-carnitine hydrochloride. This L-carnitine form focuses on muscle energy, speeds exercise recovery, and reduces muscle fatigue.

An amino acid, L-carnitine is supplied in limited quantities through a proper diet, and it is manufactured in the body, mainly in the liver and the kidneys. Supplementation offers numerous benefits as a cellular deficiency of L-carnitine can lead to symptoms such as fatigue, muscle weakness, obesity, and elevated blood lipid and triglyceride levels. Jeffrey Blan, Director of the Bellevue Medical Laboratory, has argued that proper L-carnitine supplementation while dieting can help control the negative effects of ketosis or the accumulation of waste from fat metabolism. There is also evidence that some forms of obesity may be related to a genetic propensity to produce less L-carnitine. Liver and kidney problems will similarly reduce the body's production since as much as 80% of L-carnitine is produced by these organs. Finally, L-carnitine penetrates the mitochondria, and it is here that most free radicals generated as food are oxidized to produce energy. L-carnitine protects antioxidants and reduces free-radical damage.

Chemical structure of Acetylcarnitine. Image© Jü.

Some researchers argue that supplemental L-carnitine does not increase the amount of fatty acids used for energy except in cases of a deficiency. Some of the mixed results in studies have been attributed to using the wrong forms and doses of carnitine. It's now understood that L-carnitine has two particularly active forms, although they are active for different purposes. Acetyl-L-carnitine is especially active in neuronal tissues, whereas propionyl-Lcarnitine is especially active in lean muscle tissue. The form of L-carnitine used must correspond with the particular condition or reason for its use.

Acetyl-L-carnitine is involved in the same metabolic functions as is L-carnitine in its other forms, but acetyl-L-carnitine offers greater general protection at 500 mg for the brain and nervous system. As an antioxidant, acetyl-L-carnitine protects neurons from damage caused by superoxide radicals. One reason may be that the molecular structure of acetyl-L-carnitine resembles that of the neurotransmitter, acetylcholine. Research on preventing age-related mitochondrial decay and mental ability decline, perhaps even reversing some instances of mental decline, has stressed the combination of acetyl-Lcarnitine and alpha-lipoic acid.

During strenuous exercise, a large portion of L-carnitine and unused Acetyl coenzyme A or acetyl-CoA (an important molecule in metabolism) are converted to ALCAR and CoA inside mitochondria by carnitine O-acetyltransferase. The ALCAR is transported outside the mitochondria where it converts back to the two constituents. The L-carnitine is cycled back into the mitochondria with acyl groups to facilitate fatty acid utilization, but excess acetyl-CoA may block it. Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. This occurs by different mechanisms inside and outside the mitochondria. ALCAR transport decreases acetyl-CoA inside the mitochondria, but increases it outside. Glucose metabolism increases with administration of either ALCAR or L-carnitine. A portion of L-carnitine is converted to ALCAR after ingestion in humans.

ALCAR has the ability to cross the blood-brain barrier and get to the brain blood circulation, where it acts as a powerful antioxidant, which helps in prevention of the brain cells' deterioration. Its supplementation has been shown to be neuroprotective in instances of cerebral ischemia in laboratory experiments and may be useful in treating peripheral nerve injury as well as spinal cord injury. It may have some neuroprotective benefit in the treatment of Parkinson's disease, but further research is required. ALCAR is also known to increase sperm motility, which describes the ability of sperm to move vigorously. Since motility is among the most important factors that help in the determination of sperm’s fertilization capability, acetyl-L-carnitine can help sperm cells move more actively, which consequently leads to the improved male fertility. Research into the compound's safety and efficacy in humans is required. ALCAR has been shown to be more effective than tamoxifen in improving the curvature and reducing the pain and plaque sizes for men who sought treatment for their Peyronie's disease early and having low curvature deformities. ALCAR has also been shown to improve insulin response and is proved to have a positive effect on various muscle diseases as well as heart conditions.

*Propionyl-L-carnitine has its own set of strengths. It is used to manage peripheral vascular disease, atherosclerotic and diabetic angioplasties, and congestive heart failure. In combination with acetyl-L-carnitine, propionyl-L-carnitine is used for symptoms of chronic fatigue syndrome and age-related testosterone deficiency. In fact, it seems to lessen symptoms of male hormone decline in older men, which reduces instances of sexual dysfunction, depression, and fatigue - but without the side effects of testosterone supplementation. The focus of propionyl-L-carnitine, therefore, is on the muscles, such as the heart and on the vascular system, which is particularly helpful to athletes. Compared with at least one other form, propionyl-L-carnitine appears to produce greater increases in cellular L-carnitine concentrations. Researchers believe that it is transported more easily into muscle fibers and may better support muscle-cell energy production, perhaps because it increases the flow of pyruvate (a co-factor) into the Krebs cycle* to start it. Propionyl-L-carnitine also exhibits significant free-radical scavenging activity and helps prevent blood from coagulating too readily. In short, L-carnitine helps to improve blood flow and energy to the muscles.

*The Krebs cycle, also known as the citric acid cycle, the tricarboxylic acid cycle (TCA cycle), or the Szent-Györgyi–Krebs cycle, is a part of cellular respiration. It comes after the link reaction and provides the hydrogen and electrons needed for the electron transport chain. It happens inside mitochondria.

References

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Lysiak W, Lilly K, DiLisa F, Toth PP, Bieber LL (January 1988). "Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria". The Journal of Biological Chemistry 263 (3): 1151–6.
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Giancaterini A, De Gaetano A, Mingrone G, et al. (June 2000). "Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients". Metabolism: Clinical and Experimental 49 (6): 704–8. doi:10.1053/meta.2000.6250.
Mingrone G, Greco AV, Capristo E, et al. (February 1999). "L-carnitine improves glucose disposal in type 2 diabetic patients". Journal of the American College of Nutrition 18 (1): 77–82.
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Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Acupuncture and Pain: Applying Modern Science to an Ancient Practice

2012-02-21T15:35:00.000-08:00

Qi, meridians, yin and yang. How can researchers study acupuncture, a 2,000-year-old form of Traditional Chinese Medicine (TCM) based on foreign concepts that seem impossible to measure, let alone define? To Richard Nahin, Ph.D., M.P.H., the National Center for Complementary and Alternative Medicine (NCCAM)'s Senior Advisor for Scientific Coordination and Outreach, the answer is obvious: "We don't necessarily have to understand the concepts of qi or meridians to study the safety or efficacy of acupuncture".

Harvard Medical School neuroscientist and practicing acupuncturist Vitaly Napadow, Ph.D., L.Ac., agrees. "I firmly believe that everything can be studied with the scientific method. Unfortunately, we don't currently have a 'qi meter'. So, in my research, we don't focus on meridians or qi. We take a neuroscientific approach to study how acupuncture functions through the nervous system". Using the latest technologies in neuroimaging and genomics, Dr. Napadow and other NCCAM-supported scientists are drawing a scientifically coherent picture of how acupuncture affects the body. They can see physiological effects - changes in the brain's pain centers - with acupuncture. They've observed gene expression and molecular changes in the nervous and immune systems. They hope one day to be able to predict which patients are most likely to benefit from acupuncture.

Scientists aren't ready to claim that acupuncture works for any specific disease - yet. But NCCAM-supported studies have yielded promising evidence that this ancient practice modifies perception of pain and its processing by the brain, and that it may be helpful for pain management. In the years since the 1997 National Institutes of Health (NIH) consensus statement on acupuncture concluded that more rigorous research was needed, NCCAM has supported a substantial body of research. A number of these studies have tackled the challenge of developing trial designs needed to answer practical clinical questions.

Acupuncture involves stimulating points on the body, using thin, solid, metallic needles that are manipulated by hand or by electrical stimulation. Chinese tradition teaches acupuncture practitioners that the aim is to improve levels of qi, which is considered the energy force behind all life, and restore balance in the opposing forces of yin and yang. The needles are placed along meridians, invisible energy channels described in ancient Chinese manuscripts as running the length of the body.

Acupuncture chart from Hua Shou (fl. 1340s, Ming Dynasty). This image from Shi si jing fa hui (Expression of the Fourteen Meridians). (Tokyo: Suharaya Heisuke kanko, Kyoho gan 1716). {{PD-US}} - published before 1923 and public domain in the US.

Building an Evidence Base: Clinical Research Progress "Our goal is to build a house of evidence", explains long-time NCCAM grantee Brian Berman, M.D., director of the Center for Integrative Medicine at the University of Maryland School of Medicine. To date, much of the progress in clinical research on acupuncture has come from an interdisciplinary approach that includes experts in acupuncture, clinical trial methodology, biostatistics, and relevant diseases such as osteoarthritis or carpal tunnel syndrome.

"What we've learned so far is that the most promising area for using acupuncture is pain", says Dr. Nahin. Clinical studies are showing acupuncture's efficacy for some types of pain, such as back, osteoarthritis, and postoperative pain. For example, a systematic review supports the use of acupuncture for postoperative pain management. An NCCAM-supported Phase III clinical trial led by Dr. Berman showed that acupuncture relieved pain and improved function in patients with knee osteoarthritis when it was used with standard medical care, including anti-inflammatory medications and opioid pain relievers. In a large study published in 2009, researchers found that people suffering from chronic low-back pain who received acupuncture or simulated acupuncture treatments fared better than those receiving only conventional care. Pilot studies have looked at acupuncture in posttraumatic stress disorder and chemotherapy-induced nausea and vomiting. And, the Cochrane Collaboration reviewed 11 randomized trials and found that acupuncture may be a valuable option for patients suffering from tension headaches.

But these clinical outcomes may involve more than acupoints and needles. Other aspects of the acupuncture experience may play important roles in healing, including reassurance provided by the practitioner, expectation of benefit, and the sensory experience elicited by acupuncture needling, which has been called de qi and variously described as aching, dull pain, tingling, or a heaviness. In several recent studies researchers have carefully designed their studies to compare true acupuncture to simulated acupuncture and have tried to mimic the sensory experience of true acupuncture so that patients would be unaware of whether they were receiving true or simulated acupuncture. In some of these studies, such as the 2009 study on low-back pain, both simulated acupuncture and real acupuncture produced greater benefit than standard therapy.

Acupuncture's Effect on the Brain

Fascinating results regarding the possible use of acupuncture are coming out of clinical trials, but what are the mechanisms of action behind these effects? For example, NCCAM-supported researchers are tapping into the power of genomic techniques to look at what is happening at the cellular level and study acupuncture's effect in the expression of genes involved in pain. Researchers are also harnessing cutting-edge technologies to uncover pathways in the brain involved in the body's response to acupuncture.

"We wanted to know if the brain was involved in the process and how it was involved", says Bruce Rosen, M.D., Ph.D., principal investigator of an NCCAM Center of Excellence on Acupuncture and Brain Activity at Harvard Medical School. And the time is right to approach these questions. Powerful imaging techniques, functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), and Magnetoencephalography (MET), are now available to reveal areas of the brain affected during pain and to map the impact of acupuncture in patients experiencing pain.

The study led by Dr. Napadow examined the effects of acupuncture in patients with carpal tunnel syndrome. In these participants, nonpainful stimulation of finger 3 on the right hand produced hyperactivation in the left primary sensorimotor cortex. After acupuncture, this hyperactivity was reduced. By V. Napadow, Ph.D.; used with permission "With the advent of noninvasive brain imaging we were able to begin looking at human brain response to acupuncture and start to evaluate potential mechanisms in humans", says Dr. Napadow. And they found differences in this brain response between people with chronic pain and healthy controls.

For example, in research on carpal tunnel syndrome, which can cause pain and numbness due to compression of nerves in the wrist, Dr. Napadow and colleagues performed fMRI before and after acupuncture and found that patients with carpal tunnel syndrome responded to acupuncture differently from healthy controls. Their studies, published in 2007, showed that the brain of patients with carpal tunnel syndrome responded to acupuncture needling with greater activation in an area of the brain known as the hypothalamus and deactivation in another area known as the amygdala. These two areas of the brain are involved in behavior, emotions, long-term memory, and maintenance of a persistent pain state.

A number of aspects of the acupuncture experience probably contribute to the neural effects and quite possibly to the clinical benefit. Researchers have learned that the direct effects of acupuncture may be amplified by the expectation of benefit. "We found that expectation itself is a powerful modulator of the brain", says Dr. Rosen. "Expectation seems to be as powerful an influence on reduction in pain as acupuncture needling, though it appears to work in a different network in the brain that may be complementary".

Next-Generation Studies

While researchers continue to tackle the challenges in conducting acupuncture studies, such as differences between Western and TCM diagnostic approaches, acupuncture's focus on individualized care, and finding the best possible simulated or placebo procedure, they are also working toward the next generation of studies.

"We want definitive information for health care providers and the public on when acupuncture should be used and for whom, and what types and course of therapy will show efficacy", says NCCAM's Dr. Nahin. "We want to know the most appropriate dose, how many treatments per week, and what needle points are effective so acupuncturists can use evidence-based medicine to give the best care to their patients".

Researchers would also like to know if adjuvant acupuncture could enable reduction in doses of pain medications, with fewer adverse effects of the medication.

Finally, having a test to know who would benefit from acupuncture would be a move toward personalized medicine. Researchers are using imaging studies and genomic studies to search for biomarkers to predict who would be good candidates for acupuncture. "Now we can embed brain imaging evaluation within a clinical trial to correlate clinical outcome measures with brain changes", says Dr. Napadow. "There's something about the specifics of acupuncture that seem to evoke a more dramatic response in certain parts of the brain than other kinds of sensory stimuli", Dr. Rosen says. "It suggests there's something special about acupuncture that's worth trying to understand".

Progress on Pain

NCCAM-supported studies are revealing how and when acupuncture works, such as the neurological effects of stimulation with acupuncture needles and the role expectation can play in pain. Patients who are experiencing chronic pain show different brain changes from those of healthy volunteers, an important finding for understanding overall pain processes, as well as acupuncture's effects. Acupuncture appears to affect several mechanisms in the brain and spinal cord, including those involved in pain and inflammation. Expectation of pain relief plays a role in acupuncture's impact, although it affects an area of the brain that tells the body how to deal with pain, rather than the pain-reducing areas affected by needle stimulation itself.

References

Allen JJ, Schnyer RN, Chambers AS, et al. Acupuncture for depression: a randomized controlled trial. Journal of Clinical Psychiatry. 2006;67(11):1665–1673.
Berman BM, Lao L, Langenberg P, et al. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Annals of Internal Medicine. 2004;141(12):901–910.
Cherkin DC, Sherman KJ, Avins AL, et al. A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. Archives of Internal Medicine. 2009;169(9):858–866.
Ezzo J, Richardson MA, Vickers A, et al. Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting. Cochrane Database of Systematic Reviews. 2006(2):CD002285.
Hollifield M, Sinclair-Lian N, Warner TD, et al. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial. Journal of Nervous and Mental Disease. 2007;195(6):504–513.
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Napadow V, Kettner N, Liu J, et al. Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome. Pain. 2007;130(3):254–266.
Napadow V, Kettner N, Ryan A, et al. Somatosensory cortical plasticity in carpal tunnel syndrome - a cross-sectional fMRI evaluation. NeuroImage. 2006;31(2):520–530.
Napadow V, Liu J, Li M, et al. Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture. Human Brain Mapping. 2007;28(3):159–171.
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Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Acupuncture

2012-02-21T14:55:00.000-08:00

Acupuncture is an alternative medicine originating in Ancient China that treats patients by insertion and manipulation of solid, generally thin needles in the body. According to traditional Chinese medicine, bodily functions are regulated by the flow of an energy-like entity called qi. Acupuncture aims to correct imbalances in the flow of qi by stimulation of anatomical locations on or under the skin called acupuncture points, most of which are connected by channels known as meridians. Scientific research has not found any physical or biological correlate of qi, meridians and acupuncture points, and some contemporary practitioners needle the body without using a theoretical framework.

Proponents of acupuncture believe that it promotes general health, relieves pain, treats infertility, and treats and prevents disease. Current scientific research supports its efficacy in the relief of certain types of pain and nausea, however, some systematic reviews have found these results to be equivocal. Other reviews have concluded that positive results reported for acupuncture are too small to be of clinical relevance and may be the result of inadequate experimental blinding, or can be explained by placebo effects and publication bias. Other researchers have pointed out the difficulty in designing an adequate scientific control for any placebo effect acupuncture might have due to its invasiveness. The recent development of retracting needles as a form of placebo control has resulted in a new wave of studies, the weight of evidence from which suggests acupuncture's effects are due to placebo.

There is general agreement that acupuncture is safe when administered by well-trained practitioners using sterile needles but does carry small but serious risks and adverse effects including death. The use of acupuncture for certain conditions has been tentatively endorsed by the United States National Institutes of Health (NIH) and National Center for Complementary and Alternative Medicine (NCCAM), the National Health Service of the United Kingdom, and the World Health Organization (WHO).

Key Points

Acupuncture originated in China more than 2,000 years ago, making it one of the oldest and most commonly used medical procedures in the world.
It is important to inform all of your health care providers about any treatment that you are using or considering, including acupuncture. Ask about the treatment procedures that will be used and their likelihood of success for your condition or disease.
Be an informed consumer and find out what scientific studies have been done on the effectiveness of acupuncture for your health condition.
If you decide to use acupuncture, choose the practitioner with care. Also check with your insurer to see if the services will be covered.

History

Acupuncture is one of the oldest, most commonly used medical procedures in the world. Originating in China more than 2,000 years ago, acupuncture began to become better known in the United States in 1971, when New York Times reporter James Reston wrote about how doctors in China used needles to ease his pain after surgery. The term acupuncture describes a family of procedures involving stimulation of anatomical points on the body by a variety of techniques. American practices of acupuncture incorporate medical traditions from China, Japan, Korea, and other countries. The acupuncture technique that has been most studied scientifically involves penetrating the skin with thin, solid, metallic needles that are manipulated by the hands or by electrical stimulation.

Acupuncture in the United States

In the past two decades, acupuncture has grown in popularity in the United States. The report from a Consensus Development Conference on Acupuncture held at the National Institutes of Health (NIH) in 1997 stated that acupuncture is being "widely" practiced by thousands of physicians, dentists, acupuncturists, and other practitioners for relief or prevention of pain and for various other health conditions. According to the 2002 National Health Interview Survey the largest and most comprehensive survey of complementary and alternative medicine (CAM) use by American adults to date an estimated 8.2 million U.S. adults had ever used acupuncture, and an estimated 2.1 million U.S. adults had used acupuncture in the previous year.

What Does it Feel Like?

Acupuncture needles are metallic, solid and hair-thin. People experience acupuncture differently, but most feel no or minimal pain as the needles are inserted. Some people are energized by treatment, while others feel relaxed. Improper needle placement, movement of the patient, or a defect in the needle can cause soreness and pain during treatment. This is why it is important to seek treatment from a qualified acupuncture practitioner.

Is it Safe?

The U.S. Food and Drug Administration (FDA) approved acupuncture needles for use by licensed practitioners in 1996. The FDA requires that sterile, nontoxic needles be used and that they be labeled for single use by qualified practitioners only. Relatively few complications from the use of acupuncture have been reported to the Food and Drug Administration (FDA) in light of the millions of people treated each year and the number of acupuncture needles used. Still, complications have resulted from inadequate sterilization of needles and from improper delivery of treatments. Practitioners should use a new set of disposable needles taken from a sealed package for each patient and should swab treatment sites with alcohol or another disinfectant before inserting needles. When not delivered properly, acupuncture can cause serious adverse effects, including infections and punctured organs.

Does it Really work?

According to the National Institute of Health (NIH) Consensus Statement on Acupuncture, there have been many studies on acupuncture's potential usefulness, but results have been mixed because of complexities with study design and size, as well as difficulties with choosing and using placebos or sham acupuncture. However, promising results have emerged, showing efficacy of acupuncture, for example, in adult postoperative and chemotherapy nausea and vomiting and in postoperative dental pain. There are other situations, such as addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, low-back pain, carpal tunnel syndrome, and asthma, in which acupuncture may be useful as an adjunct treatment or an acceptable alternative or be included in a comprehensive management program.

A National Center for Complementary and Alternative Medicine (NCCAM)-funded study recently showed that acupuncture provides pain relief, improves function for people with osteoarthritis of the knee, and serves as an effective complement to standard care. Further research is likely to uncover additional areas where acupuncture interventions will be useful. The NIH has funded a variety of research projects on acupuncture. These grants have been funded by NCCAM, its predecessor the Office of Alternative Medicine, and other NIH institutes and centers.

How does Acupuncture work?

Acupuncture is one of the key components of the system of Traditional Chinese Medicine (TCM). In the TCM system of medicine, the body is seen as a delicate balance of two opposing and inseparable forces: yin and yang. Yin represents the cold, slow, or passive principle, while yang represents the hot, excited, or active principle. Among the major assumptions in TCM are that health is achieved by maintaining the body in a "balanced state" and that disease is due to an internal imbalance of yin and yang. This imbalance leads to blockage in the flow of qi (vital energy) along pathways known as meridians. It is believed that there are 12 main meridians and 8 secondary meridians and that there are more than 2,000 acupuncture points on the human body that connect with them.

Preclinical studies have documented acupuncture's effects, but they have not been able to fully explain how acupuncture works within the framework of the Western system of medicine that is commonly practiced in the United States. It is proposed that acupuncture produces its effects through regulating the nervous system, thus aiding the activity of pain-killing biochemicals such as endorphins and immune system cells at specific sites in the body. In addition, studies have shown that acupuncture may alter brain chemistry by changing the release of neurotransmitters and neurohormones and, thus, affecting the parts of the central nervous system related to sensation and involuntary body functions, such as immune reactions and processes that regulate a person's blood pressure, blood flow, and body temperature.

Finding a Licensed Practitioner

Health care practitioners can be a resource for referral to acupuncturists. More medical doctors, including neurologists, anesthesiologists, and specialists in physical medicine, are becoming trained in acupuncture, TCM, and other CAM therapies. In addition, national acupuncture organizations, which can be found through libraries or Web search engines, may provide referrals to licensed acupuncture practitioners.

An acupuncture practitioner who is licensed and credentialed may provide better care than one who is not. About 40 states have established training standards for acupuncture certification, but states have varied requirements for obtaining a license to practice acupuncture. Although proper credentials do not ensure competency, they do indicate that the practitioner has met certain standards to treat patients through the use of acupuncture. Do not rely on a diagnosis of disease by an acupuncture practitioner who does not have substantial conventional medical training. If you have received a diagnosis from a licensed physician, you may wish to ask your doctor whether acupuncture might help.

Cost

A practitioner should inform you about the estimated number of treatments needed and how much each will cost. If this information is not provided, ask for it. Treatment may take place over a few days or for several weeks or more. Physician acupuncturists may charge more than nonphysician practitioners.

Insurance Coverage

Acupuncture is one of the CAM therapies that are more commonly covered by insurance. However, you should check with your insurer before you start treatment to see whether acupuncture will be covered for your condition and, if so, to what extent. Some insurance plans require preauthorization for acupuncture.

Initial Visit

During your initial or first office visit, the practitioner may ask you at length about your health condition, lifestyle, and behavior. The practitioner will want to obtain a complete picture of your treatment needs and behaviors that may contribute to your condition. Inform the acupuncturist about all treatments or medications you are taking and all medical conditions you have.

References

NIH Consensus Development Program (November 3–5, 1997). "Acupuncture --Consensus Development Conference Statement". National Institutes of Health. http://consensus.nih.gov/1997/1997Acupuncture107html.htm retrieved 2007-07-17.
Singh, S; Ernst E (2008). "The Truth about Acupuncture". Trick or treatment: The undeniable facts about alternative medicine. W. W. Norton & Company. pp. 39–90. ISBN 0393066616. "Scientists are still unable to find a shred of evidence to support the existence of meridians or Ch'i" (p72 – UK Ed.), "The traditional principles of acupuncture are deeply flawed, as there is no evidence at all to demonstrate the existence of Ch'i or meridians" (p107 – UK Ed.), "Acupuncture points and meridians are not a reality, but merely the product of an ancient Chinese philosophy" (p387 – UK Ed.)".
Bauer, M (2006). "The Final Days of Traditional Beliefs? – Part One". Chinese Medicine Times 1 (4): 31. http://www.chinesemedicinetimes.com/section.php?xSec=122.
Ahn, Andrew C.; Colbert, Agatha P.; Anderson, Belinda J.; Martinsen, ØRjan G.; Hammerschlag, Richard; Cina, Steve; Wayne, Peter M.; Langevin, Helene M. (2008). "Electrical properties of acupuncture points and meridians: A systematic review". Bioelectromagnetics 29 (4): 245–56. doi:10.1002/bem.20403. PMID 18240287. http://www.treeoflifetaichi.com/AcuPoints_Electrical.pdf
Mann, F (2000). Reinventing acupuncture: a new concept of ancient medicine. Elsevier. ISBN 0750648570.
de las Peñas, César Fernández; Arendt-Nielsen, Lars; Gerwin, Robert D (2010). Tension-type and cervicogenic headache: pathophysiology, diagnosis, and management. Jones & Bartlett Learning. pp. 251–4. ISBN 9780763752835.
Novak, Patricia D.; Dorland, Norman W.; Dorland, William Alexander Newman (1995). Dorland's Pocket Medical Dictionary (25th ed.). Philadelphia: W.B. Saunders. ISBN 0-7216-5738-9. OCLC 33123537.
"Cochrane and Alternative Medicine – Acupuncture". Danish Knowledge and Research Center for Alternative Medicines. 2011-09-28. http://www.vifab.dk/uk/cochrane+and+alternative+medicine/acupuncture? retrieved 2011-10-19.
Mayhew E; Ernst E (2007). "Acupuncture for fibromyalgia—a systematic review of randomized clinical trials". Rheumatology (Oxford, England) 46 (5): 801–4. doi:10.1093/rheumatology/kel406. PMID 17189243. http://rheumatology.oxfordjournals.org/content/46/5/801.full.pdf
Napadow, Vitaly; Ahn, Andrew; Longhurst, John; Lao, Lixing; Stener-Victorin, Elisabet; Harris, Richard; Langevin, Helene M. (2008). "The Status and Future of Acupuncture Mechanism Research". The Journal of Alternative and Complementary Medicine 14 (7): 861–9. doi:10.1089/acm.2008.SAR-3. PMC 3155097. PMID 18803495. http://www.nmr.mgh.harvard.edu/~vitaly/PDF/napadow_jacm_2004.pdf
Committee on the Use of Complementary and Alternative Medicine by the American Public (2005). Complementary and Alternative Medicine in the United States. National Academies Press. http://www.nap.edu/catalog.php?record_id=11182.
Vickers, A.; Goyal, N.; Harland, R.; Rees, R. (1998). "Do certain countries produce only positive results? A systematic review of controlled trials" (pdf). Controlled clinical trials 19 (2): 159–166. doi:10.1016/S0197-2456(97)00150-5. PMID 9551280. http://www.dcscience.net/Vickers_1998_Controlled-Clinical-Trials.pdf
Furlan, Andrea D.; Van Tulder, Maurits; Cherkin, Dan; Tsukayama, Hiroshi; Lao, Lixing; Koes, Bart; Berman, Brian (2005). "Acupuncture and Dry-Needling for Low Back Pain: An Updated Systematic Review Within the Framework of the Cochrane Collaboration". Spine 30 (8): 944–63. doi:10.1097/01.brs.0000158941.21571.01. PMID 15834340.
Steven Salzberg (2008). "Acupuncture infiltrates the University of Maryland and NEJM". http://genome.fieldofscience.com/2010/08/acupuncture-infiltrates-university-of.html
Steven Novella. "Acupuncture Pseudoscience in the New England Journal of Medicine". http://www.sciencebasedmedicine.org/?p=6391
Sampson WI (2005). "Critique of the NIH Consensus Conference on Acupuncture". Acuwatch. http://www.acuwatch.org/general/nihcritique.shtml
"Acupuncture, American Cancer Society". Cancer.org. http://www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/ManualHealingandPhysicalTouch/acupuncture retrieved 2012-02-18.
Camillia M (2006). "Seeing the Body: The Divergence of Ancient Chinese and Western Medical Illustration". Journal of Biocommunication 32 (1). http://www.sesp.northwestern.edu/docs/publications/6074956944509ac426aaa6.pdf
Becker, Robert O.; Selden, Gary (1985). The Body Electric. New York: William Morrow. ISBN 0-688-06971-1.
Colbert, A. P.; Spaulding, K.; Larsen, A.; Ahn, A. C.; Cutro, J. A. (2011). "Electrodermal Activity at Acupoints: Literature Review and Recommendations for Reporting Clinical Trials". Journal of Acupuncture and Meridian Studies 4 (1): 5–13. doi:10.1016/S2005-2901(11)60002-2. PMID 21440875
Kalichman, L.; Vulfsons, S. (2010). "Dry Needling in the Management of Musculoskeletal Pain". The Journal of the American Board of Family Medicine 23 (5): 640–6. doi:10.3122/jabfm.2010.05.090296. http://www.jabfm.com/content/23/5/640.full.pdf
Sun, Y.; Gan, T. J.; Dubose, J. W.; Habib, A. S. (2008). "Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials". British Journal of Anaesthesia 101 (2): 151–60. doi:10.1093/bja/aen146. PMID 18522936. http://bja.oxfordjournals.org/content/101/2/151.full.pdf
Paterson, C.; Dieppe, P. (2005). "Characteristic and incidental (placebo) effects in complex interventions such as acupuncture". BMJ 330 (7501): 1202–1205. doi:10.1136/bmj.330.7501.1202. PMC 558023. PMID 15905259. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=558023
"Report 12 of the Council on Scientific Affairs (A-97) – Alternative Medicine". American Medical Association. 1997. http://www.ama-assn.org/ama/no-index/about-ama/13638.shtml. Retrieved 2009-10-07
Norheim, Arne Johan (1996). "Adverse Effects of Acupuncture: A Study of the Literature for the Years 1981–1994". The Journal of Alternative and Complementary Medicine 2 (2): 291–7. doi:10.1089/acm.1996.2.291. PMID 9395661
Woo, P. C Y; Lin, A. W C; Lau, S. K P; Yuen, K.-Y. (2010). "Acupuncture transmitted infections". BMJ 340: c1268. doi:10.1136/bmj.c1268. PMID 20299695. http://www.bmj.com/content/340/bmj.c1268.full
Yamashita H, Tsukayama H, Tanno Y, Nishijo K., H; Tsukayama, H; Tanno, Y; Nishijo, K (1999). "Adverse events in acupuncture and moxibustion treatment: a six-year survey at a national clinic in Japan". J Altern Complement Med 5 (3): 229–36. doi:10.1089/acm.1999.5.229. PMID 10381246.
MacPherson H, Thomas K, Walters S, Fitter M. (2001). "The York acupuncture safety study: prospective survey of 34 000 treatments by traditional acupuncturists". Bmj 2001; 323:486. 323: 486. http://www.bmj.com/highwire/filestream/372183/field_highwire_article_pdf/0.pdf
White, A.; Hayhoe, S.; Hart, A.; Ernst, E. (2001). "Adverse events following acupuncture: prospective survey of 32 000 consultations with doctors and physiotherapists". BMJ 323 (7311): 485–6. doi:10.1136/bmj.323.7311.485. PMC 48133. PMID 11532840. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48133.
Ernst, E (2010). "Deaths after acupuncture: A systematic review". The International Journal of Risk and Safety in Medicine 22 (3): 131–6. doi:10.3233/JRS-2010-0503.
Leavy, Benjamin R. (2002). "Apparent adverse outcome of acupuncture". The Journal of the American Board of Family Practice / American Board of Family Practice 15 (3): 246–8. PMID 12038734. http://www.jabfm.org/cgi/pmidlookup?view=long&pmid=12038734
"NCCAOM Code of Ethics" (PDF). National Certification Commission for Acupuncture and Oriental Medicine. http://www.nccaom.org/about/pdfdocs/Code_of_Ethics.pdf retrieved 2010-11-03.
"Health Professions Act: Traditional Chinese Medicine Practitioners and Acupuncturists Regulation". Queen’s Printer for British Columbia. 2008-10-15. http://www.bclaws.ca/EPLibraries/bclaws_new/document/ID/freeside/32_290_2008 retrieved 2010-11-03.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Alternative Cholesterol Remedies

2012-02-21T13:34:00.000-08:00

Cholesterol is very important for healthy body function. The body uses cholesterol in the production of hormones such as estrogen, progesterone and testosterone. It is also used in the myelin sheath formation, which covers and protects the nerves. The liver makes approximately 90% of the body's daily cholesterol requirement with the remaining 10% being obtained from dietetic sources.

Cholesterol binds to different proteins and is generally transported throughout the body by means of the blood stream. Depending on the type of protein the cholesterol is bound to, it is called High Density Lipoprotein (HDL) or Low Density Lipoprotein (LDL). Low HDL in conjunction with high LDL has been linked with the formation of plaque on the arterial walls, which over time causes narrowing and hardening of the arteries. This type of arterial hardening has been associated with heart disease, and can lead to increased risk of heart attack and stroke.

Because the body requires 10% of its daily cholesterol requirements from dietetic sources, the common strategy for treating high cholesterol has been to control the intake of cholesterol. Cholesterol is found in all animal products, however some of these products such as eggs, primarily the yolks, and red meat are higher in cholesterol than other products such as poultry and fish. Therefore, by altering you dietary habits, you can reduce your intake of cholesterol.

Other methods that can help to reduce not only cholesterol levels but also blood pressure levels is to increase your daily intake of dietetic fiber and green leafy vegetables, as well as increasing your level of exercise. Studies have shown that people who exercise moderately on a daily basis exhibit higher levels of HDL (good cholesterol) and reduced levels of LDL (bad cholesterol).

Herbs such as garlic and guggul as well as other naturally occurring substances such as policosanol and niacin can have a dramatic effect on lowering levels of blood cholesterol. In several clinical studies, extract of guggul has been shown to significantly lower a person’s total blood cholesterol levels as well as their LDL levels within a period of just 6 to 12 weeks with no obvious side effects.

"Vitamin B3" (also known as niacin) has long been known as an effective supplement for use in the treatment of high cholesterol. However, when niacin was used at high enough dosages to produce a lowering effect on cholesterol it was shown to cause some undesirable side effects such as skin flushing and the risk of liver damage. Because these side effects make the use of a straight niacin supplement unacceptable as a cholesterol lowering treatment, there is a substance called inositol hexanicotinate, which is a substance chemically similar to niacin. Inositol hexanicotinate provides the cholesterol lowering benefits of straight niacin without the unacceptable side effects of skin flushing or liver damage. Clinical studies have shown that the use of inositol hexanicotinate is free of any serious side effects, however, it has been shown to cause occasional mild gastrointestinal upset in some individuals.

Originally extracted from sugar cane, and now derived from a number of other natural sources, "Policosanol", when taken in dosages ranging from 5 to 15 mg per day, has been shown to significantly lower total cholesterol levels by as much as 10 to 30% in as little as three to four weeks with no noticable side effects.

A commonly known herb that has been the focus of hundreds of studies is "Garlic". When taken in sufficient quantities, this herb has made known its dramatic effect at lowering high levels of cholesterol and blood pressure.

The downside to consuming high amounts of raw garlic of course is its propensity to cause one's breath and body odor to smell very strongly of garlic. There are so-called "odorless" garlic capsules one can substitute in place of the raw garlic, however, keep in mind that the naturally occurring chemicals found in raw garlic, and of which are responsible for causing that smelly garlic odor are the same chemicals responsible for effecting the lowering of cholesterol and blood pressure levels.

It is believed that many herbs as well as other naturally derived substances can work to reduce the level of cholesterol in a person's blood. By implementing a smart supplementation approach in combination with a sensible diet and exercise program, you may find that a positive change can be noted in your overall cholesterol levels.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Eat a Rainbow of Foods

2012-02-21T13:10:00.000-08:00

If you want to improve your health add a rainbow of healthy foods to your next meal!

ChooseMyPlate.gov. Image is the work of the USDA

Choose My Plate.gov Guidelines

Balancing Calories:

Enjoy your food, but eat less.
Avoid oversized portions.

Foods to Increase:

Make half your plate fruits and vegetables.
Make at least half your grains whole grains.
Switch to fat-free or low-fat (1%) milk.

Foods to Reduce:

Compare sodium in foods like soup, bread, and frozen meals - and choose the foods with lower numbers.
Drink water instead of sugary drinks.

The more colorful fruits or vegetables are in nature, the more likely they are to contain larger quantities of phytonutrients such as antioxidants, vitamins and minerals. These phytonutrients play a huge role in one’s health by helping to lower the risk of numerous health problems, and they can even assist with shedding some of those unwanted pounds.

BLUE and PURPLE foods: Eating a 1/2 cup of blueberries twice a week can enhance memory and improve motor skills. So, go ahead and sprinkle fresh blueberries over your morning cereal, mix them into yogurt, or enjoy a couple of blueberry muffins. Purple cabbage contains isothiocyanates, which are powerful pigments that help lower your risk of cancer, especially breast cancer. Research has shown that women who ate at least four servings of purple cabbage a week reduced their chances of developing cancer of the breast by 65%. Also, drinking an eight-ounce glass of grape juice two or three times a week can help lower high blood pressure, detoxify the system, and even help with weight loss.

ORANGE foods: What better way to start the day than by eating segments of a delicious orange or drinking a tall glass of freshly squeezed orange juice. We all know that oranges contain high amounts of vitamin C, but did you also know that the peel contains hesperidin, a naturally occurring chemical that can help to lower blood pressure and cholesterol levels, and reduce inflammation, which can lead to many health problems including food sensitivities or allergies, respiratory problems such as asthma, heart disease, and even certain cancers. Add some orange peel to your favorite hot tea, or grate it over salads, or add it as a garnish to desserts to reap the powerful health benefits. Sweet potatoes and yams are not only fat free, they are a wonderful source of vitamin E, and they are higher in vitamins and minerals than any other vegetable. Carrots contain a group of pigments called beta-carotene. Research shows that when a person eats a raw carrot only 5% of these pigments are absorbed into the system, but when a person drinks the juice of this vegetable the body absorbs 90% of the beta-carotene it contains.

A Rainbow of Healthy Foods

GREEN foods: Research shows that people who suffer from asthma can reduce the wheezing, runny nose, and shortness of breath by as much as 40% when they eat four to six kiwis a week. Cut the top off this yummy food and eat it with a spoon like a soft-boiled egg. Low calorie vegetables like spinach, kale, broccoli and green peppers are loaded with fiber and powerful indoles, which can help break down cancer causing toxins in the body.

RED foods: The old saying "an apple a day..." is true. Research studies show that eating one apple a day or having a dish of applesauce (with a sprinkle of cinnamon) can lower cholesterol levels, protect the skin from sun damaging UV rays, and reduce the risk of heart disease and certain cancers.

YELLOW foods: Did you know that if you are feeling sad you should eat a banana? Studies show that people suffering from mild to moderate depression (not manic depressive/bipolar conditions) experienced a mood lift after eating just one banana. How does this work? Well, the answer the answer lies within a naturally occurring chemical in the banana called trytophan, which helps increase production of serotonin - the human body's 'feel good' hormone. The high iron content in bananas also helps to ward off anemia. Drinking a small glass of grapefruit juice before each meal can help to curb your appetite, and in so doing, may help you to lose a few of those unwanted pounds. Squash, especially butternut squash, contains high amounts of carotenoids, which when eaten once a week, can help to lower your risk for certain cancers, especially lung cancer.

References

Agency for Healthcare Research and Quality. Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cancer. Evidence Report/Technology Assessment no. 75. Rockville, MD: Agency for Healthcare Research and Quality; 2003. AHRQ publication no. 04-E002.
Agency for Healthcare Research and Quality. Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Disease. Evidence Report/Technology Assessment no. 83. Rockville, MD: Agency for Healthcare Research and Quality; 2003. AHRQ publication no. 03-E043.
Antioxidants and cancer prevention: fact sheet. National Cancer Institute.
Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. 2008;(2):CD007176.
Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Archives of Internal Medicine. 2007;167(15):1610–1618.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Antioxidant Supplements for Health

2012-02-21T12:37:00.000-08:00

Antioxidants are substances that may prevent potentially disease-producing cell damage that can result from natural bodily processes and from exposure to certain chemicals. There are a number of different antioxidants found in foods and available as dietary supplements. This fact sheet provides a general overview of antioxidants, with a focus on dietary supplements, and suggests sources for additional information.

Key Points

People take antioxidant supplements in an effort to improve their health and to prevent various diseases. Examples of commonly used antioxidant supplements include vitamins C and E, selenium, and beta-carotene.
Although observational studies suggest that eating a diet high in antioxidant-rich vegetables and fruits is associated with a lower risk for many chronic diseases, there is limited evidence to support the use of antioxidant supplements to prevent disease. Additional research, including studies supported by the National Center for Complementary and Alternative Medicine and other components of the National Institutes of Health is under way.
Tell all of your health care providers about any complementary and alternative practices you use, including antioxidant supplements. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.

About Antioxidants

Oxidation, one of the body's natural chemical processes, can produce free radicals, which are highly unstable molecules that can damage cells. For example, free radicals are produced when the body breaks down foods for use or storage. They are also produced when the body is exposed to tobacco smoke, radiation, and environmental contaminants. Free radicals can cause damage, known as "oxidative stress," which is thought to play a role in the development of many diseases, including Alzheimer's disease, cancer, eye disease, heart disease, Parkinson's disease, and rheumatoid arthritis. In laboratory experiments, antioxidant molecules counter oxidative stress and its associated damage.

The body can produce its own antioxidants and also obtain them from food. Antioxidants are abundant in vegetables and fruits and are also found in grain cereals, teas, legumes, and nuts. Examples of antioxidants include anthocyanins, beta-carotene, catechins, coenzyme Q10, flavonoids, lipoic acid, lutein, lycopene, selenium, and vitamins C and E. Many antioxidants are also available as dietary supplements.

Although antioxidant molecules counter oxidative stress in controlled laboratory experiments, there is some debate as to whether consuming antioxidants, in food or supplement form, actually benefits health. Antioxidant supplements are often synthetic (man-made), but some of these synthetic forms may not have the same effects on the body as antioxidants that occur naturally in foods. In addition, some beneficial properties may be lost when antioxidants are extracted from foods to manufacture supplements. There is also some concern that consuming antioxidants in excessive doses may have negative effects.

Use of Antioxidant Supplements in the United States

In the National Health and Nutrition Examination Survey (NHANES, 1999–2000), over 5,000 of the approximately 10,000 respondents (52 percent), reported taking a dietary supplement in the previous month. Of the 1,900 dietary supplements included in the survey, more than 900 (47 percent) contained an antioxidant: vitamin C, vitamin E, beta-carotene, selenium, flavonoids, or isoflavones. More than 3,000 of the respondents (37 percent) reported taking dietary supplements that contained one of the antioxidants mentioned. A 2009 study looked at data from NHANES (1999-2000 and 2001-2002) and the U.S. Department of Agriculture Flavonoid Database to estimate the total antioxidant intake (from diet and supplements) of adults in the United States. The researchers calculated the daily intake of vitamin C, vitamin E, carotenes, selenium, and flavonoids. They found that supplements accounted for 54 percent of vitamin C; 64 percent of vitamin E (alpha-tocopherol); 14 percent of carotenes; 11 percent of selenium; and 2 percent of flavonoid intake.

Status of Research on Antioxidant Supplements

There is limited scientific evidence to support the use of antioxidant supplements to prevent disease. Observational studies (which track a group of people without changing their activities or providing special treatments) have shown that a higher intake of antioxidant-rich vegetables and fruits is associated with a reduced risk of certain chronic diseases. It is not clear, however, that the benefits are due to the antioxidants. Although observational studies, as well as laboratory research on the biochemistry of antioxidants, suggest that antioxidant supplements may have beneficial effects, clinical trials (controlled studies in people) have generally found no benefit.

Systematic reviews of the research literature have analyzed the use of antioxidant supplements for preventing cancer, cardiovascular disease, and eye disease, and reducing overall mortality in healthy people and people with various diseases. In general, these reviews have concluded that there is not enough evidence to support the use of antioxidant supplements for these purposes.

MultiVitamin/MultiMineral Dietary Supplement

Large, long-term studies (randomized, controlled trials) funded primarily by the National Institutes of Health have generally found that antioxidant supplements have no beneficial effects. For example:

The Physicians Health Study II, which included more than 14,000 healthy male physicians aged 50 or older, found that neither vitamin E nor vitamin C supplements reduced the risk of major cardiovascular events (e.g., heart attack, stroke, or death) or cancer.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT), a study of more than 35,000 healthy men aged 50 or older, found that selenium and vitamin E taken alone or together did not prevent prostate cancer. (Two earlier reviews suggested that preliminary evidence for selenium appeared promising).
The Women's Health Study, which included almost 40,000 healthy women at least 45 years of age, found that overall, vitamin E did not reduce the risk of death, major cardiovascular events (e.g., heart attack, stroke, or death), or cancer. However, it was associated with reduced deaths from cardiovascular causes and also reduced major cardiovascular events in a subgroup of women aged 65 or older.
The Women's Antioxidant Cardiovascular Study found no beneficial effects of vitamin C, vitamin E, or beta-carotene on cardiovascular events (e.g., heart attack, stroke, or death) in more than 8,000 female health professionals, aged 40 years or older, who were at high risk for cardiovascular disease.

An important exception to this trend is a National Eye Institute study of age-related eye disease, which found that the combination of antioxidants and zinc reduced the risk of developing advanced stages of age-related macular degeneration (AMD) by 25 percent in people who had intermediate AMD or advanced AMD in only one eye. Antioxidant supplements used alone reduced the risk by about 17 percent.

Thus, despite widespread scientific interest and clear plausibility of benefit, the body of evidence for antioxidant supplements has not, to date, demonstrated substantial health benefits. Additional research, some of it aimed at understanding the "disconnect" between findings of laboratory and observational studies and results of clinical trials, is under way.

Safety: Antioxidant Supplements

Antioxidants in foods are generally considered safe, and studies of antioxidant supplements generally have not reported adverse effects. However, the research does point to some potential concerns; for example, beta-carotene supplements may increase the risk of lung cancer in smokers, and vitamin E supplements may increase the risk of bleeding in certain individuals. More research is needed to better understand the safety aspects of dietary supplementation.

If you are thinking about using antioxidant supplements:

Do not use antioxidant supplements as a replacement for a healthful diet or conventional medical care, or as a reason to postpone seeing a doctor about a medical problem.
Consult your health care provider before deciding to use antioxidant supplements.
Look for published research studies on antioxidant supplements for the health condition that interests you.
Tell all of your health care providers about any complementary and alternative practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.

Because antioxidants are widely used, and because there is laboratory and observational evidence of potential health benefits, antioxidants are the subject of extensive research across the National Institutes of Health (NIH), including recent National Center for Complementary and Alternative Medicine (NCCAM) sponsored studies that have been investigating:

Three antioxidant regimens, ginkgo biloba, alpha-lipoic acid/essential fatty acids, and vitamin E/selenium, as potential treatments for multiple sclerosis.
Lipoic acid, an antioxidant used in the treatment of diabetic neuropathy, to improve blood vessel reactivity and decrease oxidative stress in people with high cholesterol.
The safety of the vitamin E supplement gamma-tocopherol in healthy people and those with asthma and allergies.
The combination of vitamins E and C to enhance airway antioxidant levels in people with allergic asthma and reduce the incidence of preeclampsia among pregnant women with chronic hypertension or a history of preeclampsia/eclampsia.
Alpha-lipoic acid and fish oil to slow the progression of Alzheimer's disease.
Whether alpha-tocopherol (vitamin E) supplementation affects the progression of carotid atherosclerosis (narrowing or hardening of the carotid artery) in patients with coronary artery disease.
The safety and efficacy of vitamin E in slowing the rate of cognitive and functional decline in older persons with Down syndrome.

NCCAM also funds two research centers that are studying the effects of antioxidants on aging, amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig's disease), asthma, and cardiovascular diseases.

Other NIH studies on antioxidants have been investigating:

The effects of vitamin C on the lung development and function of babies born to women who smoke during pregnancy.
Whether an antioxidant drug (n-acetylcysteine) taken orally will improve glucose tolerance and insulin secretion in type 2 diabetic subjects.
The safety and effectiveness of coenzyme Q10 (combined with vitamin E) to slow the progression of Parkinson's disease.
The side effects and best dose of high-selenium Brassica juncea (mustard plant) and capecitabine (a cancer drug) given together with irinotecan (a cancer drug) as a treatment for patients with advanced cancer.
Whether antioxidants (beta-carotene, vitamin C, and vitamin E) combined with magnesium can prevent noise-induced hearing loss.

Antioxidants

2012-02-21T12:12:00.000-08:00

The fountain of youth can be found in healthy real foods. Eating a wide variety of antioxidant-rich foods may help to protect your body and reduce your risk of developing certain types of diseases. Many foods, such as wild blueberries, have very powerful antioxidant properties due to the fact that they contain oligomeric proanthocyanidins or anthocyanidins, which are naturally occurring chemical compounds within a group of plant-derived substances called flavonoids.

What Are Antioxidants?

Antioxidants are comprised of phytochemicals, which are chemical elements naturally found in medicinal herbs and plants. These phytochemicals include vitamins, minerals, and other nutrient-type sources, many of which have long provided plants with protection against disease, and now research has found that they also work in a similar fashion in the human body, helping to protect it against damage from harmful free radicals.

How Do Antioxidants Work?

Antioxidants work by neutralizing harmful free radicals in the human body. These free radicals can damage the tissues, cells, and DNA, and they may prove to be quite useful in the prevention of or treatment of some conditions such as certain types of cancers, Alzheimer’s disease, age-related vision problems such as cataracts or macular degeneration, or other diseases or conditions. The concept that antioxidants are good for your whole body is the result of years of numerous research studies and clinical trials, which have shown that individuals who have long consumed – on a daily basis – antioxidants that exist in ‘real foods’ (not in a supplement or pill form), display a marked improvement in their over-all health.

How Am I Exposed To These Harmful Free Radicals?

Exposure to these damaging free radicals can occur through several ways including the by-products of normal energy-producing mechanical processes that take place within the body, such as the release of digestive enzymes to break down food, the break down of certain prescription or over the counter (OTC) medications, and through the burning of sugars for energy. Exposure to these harmful oxygen molecules can also occur through various pollutants such as cigarette smoke. Harmful free radicals can also form in a person’s body by way of excessive exposure to the sun or to cigarette smoke. To protect your whole body, add plenty of antioxidant-rich foods to your diet. For additional skin protection, initiate a smoking cessation plan (if you smoke), and when you are outdoors in the sun, wear lightweight protective clothing, a wide-brim hat, and apply a sunscreen that contains a high sun protection factor (SPF) of at least 30.

How Safe Are Antioxidants?

Getting your fair share of antioxidants on a daily basis from real foods is considered to be quite safe. For most people, the average daily serving of fruits and vegetables is 5 to 9. If you are considering the use of dietary supplements to supply your daily source of antioxidants, it is important to know that the U.S. Food and Drug Administration (FDA) places dietary supplements in a special category of foods not drugs and requires that they be labeled as a dietary supplement. This means that whatever form the supplement is in, such as capsules, powder, liquid, tablets, or even as an energy bar, the FDA does not regulate them in the way it regulates pharmaceutical drugs, therefore, a dietary supplement can be sold over the counter (OTC) with very little or no degree of research data as to its quality or how safe it really is. Because no single antioxidant dietary supplement alone can protect the body against damage caused by these harmful oxygen molecules, a wide variety of different supplements need to be taken, often in high doses, in order to get the same antioxidant protection as one would get from eating a daily diet high in fruits and vegetables.

Keep the following information in mind should you decide to use dietary supplements on a daily basis to supply antioxidant protection or to provide additional nutrient-type support to your diet:

Like many pharmaceutical medications, dietary supplements may cause allergic reactions and/or have side effects. Most are formulated for adult administration, and very few are specifically formulated for children. They can interact with prescription medications, over the counter (OTC) preperations, other dietary supplements, or herbal remedies you might be using, which could possibly cause your health condition to worsen.

Dietary supplements are just that – supplementary – and they should not be used long-term or as a substitute for the wide variety of "real foods" important to a healthy well balanced diet. Always inform your physician or qualified health care practitioner if you are currently taking a dietary supplement, or if you are considering the use of a dietary supplement along with your prescription medication, or if you are thinking of giving up your present medication entirely and switching completely over to supplements, as this may not be a safe treatment option and could be dangerous, especially if your condition is serious.

What Foods Are Rich In Antioxidants?

Some of the top ranking antioxidant-rich foods include walnuts, artichokes, pecans, chocolate (dark-unsweetened), grapes (purple), cherries (sour), pineapple, guava, prunes, cabbage (red-cooked), oranges, apples, mangoes, plums, beans (pinto), spinach, whole grain breads, and berries (strawberries, blackberries, raspberries, cranberries, and blueberries). Coffee, tea, and red wine are also high in antioxidants, as are ground cloves (used in culinary as a spice).

"Foods highest in antioxidants". Image or file is a work of United States Department of Agriculture (USDA)

The subsequent information provides an example of good nutrient-type sources of antioxidants, and how they may work to protect the body. For additional information on supplement interactions, adverse effects, and cautions/contraindications regarding these and other nutrient-type sources, refer to the book Let’s Get Natural with Herbs by Debra J. Rayburn. For more antioxidant-rich food sources, read on...

CAROTENOIDS are a similarly colored pigment (yellowish-orange) and closely related to carotene. Carotenoids may be converted or changed into vitamin A in the body, which encourages the growth of healthy cells and tissues, promotes normal vision, and helps protect the body against infection. Carotenoids may reduce the risk of certain types of cancers, as well as some age-related vision problems such as cataracts and macular degeneration. ‘Real food’ sources high in carotenoids and vitamin A include peppers (yellow, red, and orange), potatoes (sweet), spinach, mango, carrots, broccoli, cantaloupe, lettuce (romaine), tomatoes, other leafy greens, fish oils, egg yolk, liver, and cheeses. Note: carotenemia or an excess presence of carotene in the blood can produce a yellowish pigmentation of the skin resembling jaundice. Avoid the use of vitamin A supplements during pregnancy as they may cause spontaneous abortion or serious birth defects. Avoid the use of vitamin A supplements if you have depression (it may cause the condition to worsen), or if you are undergoing chemotherapy.

VITAMIN C or ascorbic acid plays an important role in the formation of collagen (the main supportive protein of bone, tendon, cartilage, connective tissue, and skin). It may promote vascular system health, aid in the assimilation of folic acid (folate) and iron, and it is anticoagulant. Vitamin C may be useful to protect the body against infection, gum disease, scurvy, certain types of age-related vision problems such as cataracts, and it is one of the organic compound products of pancreatic digestion or that process which is performed by the secretions of the pancreas. ‘Real food’ sources high in vitamin C include strawberries, tomatoes, oranges, peppers (red and green), broccoli, papaya, lemons, and grapefruit. Note: notify your healthcare professional prior to any lab work if you are taking vitamin C, as this supplement can cause false results in some tests. When extra-large doses* of ascorbic acid are administered intravenously* for certain conditions, such as in acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV), and schizophrenia, it may prove useful as an adjunct in their treatment to either put the disease in remission or reverse the condition, also, supplementation of 50-mg. pyridoxine (vit. B6) or calcium/magnesium tablets three times per day is recommended to protect against the formation of kidney stones.

VITAMIN E or alpha-tocopherol protects against the formation of arterial plaque, and it may offer some protection against certain types of cancers and other diseases. ‘Real food’ sources high in vitamin E include wheat germ (oil), whole grain products (breads, cereals), egg yolk, liver (beef), and a variety of seeds and nuts such as almonds and peanuts. Note: avoid excessive use of vitamin E supplements if you have a coagulation problem, diabetes, or hyperthyroidism. Because tocopherol is only stored for a short time in the body it should be taken with zinc to maintain levels in the blood. Vitamin E and iron supplements should be taken at least eight hours apart. Administration of extra-large doses of vitamin E may prove useful as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's Disease, and other degenerative diseases. Vitamin E may interfere with iron absorption, so if you are taking an individual vitamin E supplement, be sure to space it at least six to eight hours apart from the iron supplement.

SELENIUM is a mineral element that works with vitamin E and functions as an antioxidant to aid in healthy cell growth, enhance the immune system, and protect against heart disease (in high risk individuals). It activates DNA and RNA, creates antibodies, enhances immune system function, and it strengthens the cardiovascular system. Muscular dystrophy, heart disease, infertility, skin problems, and apoplectic stroke may indicate a selenium deficiency. ‘Real food’ sources high in selenium include poultry, cottage cheese, nuts (brazil), meats, breads (whole wheat), seafood, eggs, and pasta (whole wheat). Note: compounds of selenium have been used experimentally as an adjunct in the treatment of certain tumors. Supplement interaction: taking individual selenium and copper supplements at the same time could result in an interaction. If you are taking individual mineral supplements, it is best to space them at least six to eight hours apart from one another throughout the day.

MAGNESIUM is a mineral element essential in nutrition, and it is necessary for enzyme action, muscle function, the transmission of nerve impulses, and the proper use of calcium, phosphorous, and potassium. Magnesium aids in healthy bone, nerve, tissue, and tooth growth, it balances the body’s acid/alkaline levels, enhances metabolism, reduces blood pressure levels, relaxes the nervous system, helps regulate parathyroid hormone function, protects the arterial lining, protects against heart attack (in high risk individuals), and protects against the formation of gallstones and kidney stones. Arrhythmia (heart palpitations), cravings for chocolate, confusion, debility, nervousness, and muscular cramps and twitches may indicate a magnesium deficiency. ‘Real food’ sources high in magnesium include parsnips, peas (black-eyed), beans (lima), spinach, pecans, pasta (whole wheat), and breads (whole wheat). Note: avoid use of magnesium supplements if you have diabetes, heart disease, or a kidney problem, or if you have had intestinal surgery, or if you are taking medication to slow intestinal movement.

COPPER is a mineral element that works as an antioxidant and helps in the formation of bones, elastin (a fibrous protein that provides supportive or protective functions in the body), enzymes, hemoglobin, and collagen. Copper is an important mineral in the pigmentation or coloring of skin and hair, the sensation of taste, the healing of wounds, and it fortifies the reproductive and nervous systems. It assists in the absorption and use of iron and vitamin C. Osteoporosis may be an early indication of a copper deficiency. ‘Real food’ sources high in copper include sunflower seeds, liver (beef), peanuts, mushrooms (fresh or canned), and clams. Note: avoid high doses or long-term use. Copper is best obtained through a multi-vitamin/mineral supplement. Supplement interaction: taking individual copper and selenium supplements at the same time could result in an adverse interaction. If you are taking individual mineral supplements, it is best to space them at least six to eight hours apart from one another throughout the day.

ZINC is a mineral element necessary for proper immune system function. It aids in the healing of wounds, cell regeneration, and the transportation of vitamin A from its storage site in the liver. Zinc controls the contraction of muscles, it plays a factor in DNA synthesis, protects against diabetes and liver toxicity, reduces inflammation and memory/cognitive problems, regulates the body’s pH levels and enzymatic flow in the cells, and it helps in the formation of insulin and the metabolism of carbohydrates, fats, and proteins. White spots on the fingernails may indicate a zinc deficiency 'Real food' sources high in zinc include almonds, meats, dairy products such as milk, seafood, liver, wheat bran, soy products such as tofu, and peas (black-eyed). Note: zinc may interfere with iron absorption, so if you are taking an individual zinc supplement, be sure to space it at least six to eight hours apart from the iron supplement. An excess presence of zinc in the blood can cause zincalism or chronic zinc poisoning. Avoid high doses or long-term uses.

*Supplements in extra-large doses that are administered for certain conditions are intended for professional use only. Supplements in extra-large doses that are administered via intravenous injections are intended for professional use only.

References

Agency for Healthcare Research and Quality. Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cancer. Evidence Report/Technology Assessment no. 75. Rockville, MD: Agency for Healthcare Research and Quality; 2003. AHRQ publication no. 04-E002.
Agency for Healthcare Research and Quality. Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Disease. Evidence Report/Technology Assessment no. 83. Rockville, MD: Agency for Healthcare Research and Quality; 2003. AHRQ publication no. 03-E043.
Antioxidants and cancer prevention: fact sheet. National Cancer Institute Web site.
Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. 2008;(2):CD007176.
Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Archives of Internal Medicine. 2007;167(15):1610–1618.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Electromagnetic Fields and Public Health

2012-02-20T13:17:00.000-08:00

Electromagnetic Fields and Public Health: Exposure to extremely low frequency fields
Fact sheet N°322
June 2007
Source: http://www.who.int/mediacentre/ World Health Organization (WHO)

The use of electricity has become an integral part of everyday life. Whenever electricity flows, both electric and magnetic fields exist close to the lines that carry electricity, and close to appliances. Since the late 1970s, questions have been raised whether exposure to these extremely low frequency (ELF) electric and magnetic fields (EMF) produces adverse health consequences. Since then, much research has been done, successfully resolving important issues and narrowing the focus of future research. In 1996, the World Health Organization (WHO) established the International Electromagnetic Fields Project to investigate potential health risks associated with technologies emitting EMF. A WHO Task Group recently concluded a review of the health implications of ELF fields (WHO, 2007).

Rural area - low voltage telephone poles

This Fact Sheet is based on the findings of that Task Group and updates recent reviews on the health effects of ELF EMF published in 2002 by the International Agency for Research on Cancer (IARC), established under the auspices of WHO, and by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) in 2003.

ELF field sources and residential exposures

Electric and magnetic fields exist wherever electric current flows - in power lines and cables, residential wiring and electrical appliances. Electric fields arise from electric charges, are measured in volts per metre (V/m) and are shielded by common materials, such as wood and metal. Magnetic fields arise from the motion of electric charges (i.e. a current), are expressed in tesla (T), or more commonly in millitesla (mT) or microtesla (µT). In some countries another unit called the gauss, (G), is commonly used (10,000 G = 1 T). These fields are not shielded by most common materials, and pass easily through them. Both types of fields are strongest close to the source and diminish with distance.

Most electric power operates at a frequency of 50 or 60 cycles per second, or hertz (Hz). Close to certain appliances, the magnetic field values can be of the order of a few hundred microtesla. Underneath power lines, magnetic fields can be about 20 µT and electric fields can be several thousand volts per metre. However, average residential power-frequency magnetic fields in homes are much lower - about 0.07 µT in Europe and 0.11 µT in North America. Mean values of the electric field in the home are up to several tens of volts per metre.

Task group evaluation

In October 2005, WHO convened a Task Group of scientific experts to assess any risks to health that might exist from exposure to ELF electric and magnetic fields in the frequency range >0 to 100,000 Hz (100 kHz). While IARC examined the evidence regarding cancer in 2002, this Task Group reviewed evidence for a number of health effects, and updated the evidence regarding cancer. The conclusions and recommendations of the Task Group are presented in a WHO Environmental Health Criteria (EHC) monograph (WHO, 2007).

Following a standard health risk assessment process, the Task Group concluded that there are no substantive health issues related to ELF electric fields at levels generally encountered by members of the public. Thus the remainder of this fact sheet addresses predominantly the effects of exposure to ELF magnetic fields.

Short-term effects

There are established biological effects from acute exposure at high levels (well above 100 µT) that are explained by recognized biophysical mechanisms. External ELF magnetic fields induce electric fields and currents in the body which, at very high field strengths, cause nerve and muscle stimulation and changes in nerve cell excitability in the central nervous system.

Potential long-term effects

Much of the scientific research examining long-term risks from ELF magnetic field exposure has focused on childhood leukaemia. In 2002, IARC published a monograph classifying ELF magnetic fields as "possibly carcinogenic to humans". This classification is used to denote an agent for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence for carcinogenicity in experimental animals (other examples include coffee and welding fumes). This classification was based on pooled analyses of epidemiological studies demonstrating a consistent pattern of a two-fold increase in childhood leukaemia associated with average exposure to residential power-frequency magnetic field above 0.3 to 0.4 µT. The Task Group concluded that additional studies since then do not alter the status of this classification.

However, the epidemiological evidence is weakened by methodological problems, such as potential selection bias. In addition, there are no accepted biophysical mechanisms that would suggest that low-level exposures are involved in cancer development. Thus, if there were any effects from exposures to these low-level fields, it would have to be through a biological mechanism that is as yet unknown. Additionally, animal studies have been largely negative. Thus, on balance, the evidence related to childhood leukaemia is not strong enough to be considered causal.

Childhood leukaemia is a comparatively rare disease with a total annual number of new cases estimated to be 49,000 worldwide in 2000. Average magnetic field exposures above 0.3 μT in homes are rare: it is estimated that only between 1% and 4% of children live in such conditions. If the association between magnetic fields and childhood leukaemia is causal, the number of cases worldwide that might be attributable to magnetic field exposure is estimated to range from 100 to 2400 cases per year, based on values for the year 2000, representing 0.2 to 4.95% of the total incidence for that year. Thus, if ELF magnetic fields actually do increase the risk of the disease, when considered in a global context, the impact on public health of ELF EMF exposure would be limited.

A number of other adverse health effects have been studied for possible association with ELF magnetic field exposure. These include other childhood cancers, cancers in adults, depression, suicide, cardiovascular disorders, reproductive dysfunction, developmental disorders, immunological modifications, neurobehavioural effects and neurodegenerative disease. The WHO Task Group concluded that scientific evidence supporting an association between ELF magnetic field exposure and all of these health effects is much weaker than for childhood leukaemia. In some instances (i.e. for cardiovascular disease or breast cancer) the evidence suggests that these fields do not cause them.

International exposure guidelines

Health effects related to short-term, high-level exposure have been established and form the basis of two international exposure limit guidelines (ICNIRP, 1998; IEEE, 2002). At present, these bodies consider the scientific evidence related to possible health effects from long-term, low-level exposure to ELF fields insufficient to justify lowering these quantitative exposure limits.

WHO's guidance

For high-level short-term exposures to EMF, adverse health effects have been scientifically established (ICNIRP, 2003). International exposure guidelines designed to protect workers and the public from these effects should be adopted by policy makers. EMF protection programs should include exposure measurements from sources where exposures might be expected to exceed limit values.

Regarding long-term effects, given the weakness of the evidence for a link between exposure to ELF magnetic fields and childhood leukaemia, the benefits of exposure reduction on health are unclear. In view of this situation, the following recommendations are given:

Government and industry should monitor science and promote research programmes to further reduce the uncertainty of the scientific evidence on the health effects of ELF field exposure. Through the ELF risk assessment process, gaps in knowledge have been identified and these form the basis of a new research agenda.

Member States are encouraged to establish effective and open communication programmes with all stakeholders to enable informed decision-making. These may include improving coordination and consultation among industry, local government, and citizens in the planning process for ELF EMF-emitting facilities.

When constructing new facilities and designing new equipment, including appliances, low-cost ways of reducing exposures may be explored. Appropriate exposure reduction measures will vary from one country to another. However, policies based on the adoption of arbitrary low exposure limits are not warranted.

Further reading

WHO - World Health Organization. Extremely low frequency fields. Environmental Health Criteria, Vol. 238. Geneva, World Health Organization, 2007.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Non-ionizing radiation, Part 1: Static and extremely low-frequency (ELF) electric and magnetic fields. Lyon, IARC, 2002 (Monographs on the Evaluation of Carcinogenic Risks to Humans, 80).

ICNIRP - International Commission on Non-Ionizing Radiation Protection. Exposure to static and low frequency electromagnetic fields, biological effects and health consequences (0-100 kHz). Bernhardt JH et al., eds. Oberschleissheim, International Commission on Non-ionizing Radiation Protection, 2003 (ICNIRP 13/2003).

ICNIRP – International Commission on Non-Ionizing Radiation Protection (1998). Guidelines for limiting exposure to time varying electric, magnetic and electromagnetic fields (up to 300 GHz). Health Physics 74(4), 494-522.

IEEE Standards Coordinating Committee 28. IEEE standard for safety levels with respect to human exposure to electromagnetic fields, 0-3 kHz. New York, NY, IEEE - The Institute of Electrical and Electronics Engineers, 2002 (IEEE Std C95.6-2002).

For more information contact:

WHO Media centre
Telephone: +41 22 791 2222
E-mail: mediainquiries@who.int

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Leukemia

2012-02-20T12:36:00.000-08:00

Leukemia (American English) or leukaemia (British English) or Leukämie (German) from the Greek leukos λεύκος - white, and haima αίμα - blood is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called blasts. Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases affecting the blood, bone marrow, heart, and lymphoid system, which are all known as hematological neoplasms. Leukemia can also cause multiple organ failure. In 2000, approximately 256,000 children and adults around the world developed some form of leukemia, and 209,000 died from it.

A Wright's stained bone marrow aspirate smear from a patient with precursor B-cell acute lymphoblastic leukemia. Photo© VashiDonsk.

Classification

Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its acute and chronic forms:

Acute leukemia is characterized by a rapid increase in the numbers of immature blood cells. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.
Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

Additionally, the diseases are subdivided according to which kind of blood cell is affected. This split divides leukemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:

In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.

Combining these two classifications provides a total of four main categories. Within each of these four main categories, there are typically several subcategories. Finally, some rarer types are usually considered to be outside of this classification scheme.

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Standard treatments involve chemotherapy and radiotherapy. The survival rates vary by age: 85% in children and 50% in adults.  Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia.

Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 75%.  It is incurable, but there are many effective treatments. One subtype is B-cell prolymphocytic leukemia, a more aggressive disease.

Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The five-year survival rate is 40%.  Subtypes of AML include acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.

Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease. Treatment is with imatinib (Gleevec in US, Glivec in Europe) or other drugs. The five-year survival rate is 90%.  One subtype is chronic monocytic leukemia.

Hairy cell leukemia (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern. About 80% of affected people are adult men. There are no reported cases in children. HCL is incurable, but easily treatable. Survival is 96% to 100% at ten years.

T-cell prolymphocytic leukemia (T-PLL) is a very rare and aggressive leukemia affecting adults; somewhat more men than women are diagnosed with this disease.  Despite its overall rarity, it is also the most common type of mature T cell leukemia; nearly all other leukemias involve B cells. It is difficult to treat, and the median survival is measured in months.

Large granular lymphocytic leukemia may involve either T-cells or NK cells; like hairy cell leukemia, which involves solely B cells, it is a rare and indolent (not aggressive) leukemia.

Adult T-cell leukemia is caused by human T-lymphotropic virus (HTLV), a virus similar to HIV. Like HIV, HTLV infects CD4+ T-cells and replicates within them; however, unlike HIV, it does not destroy them. Instead, HTLV "immortalizes" the infected T-cells, giving them the ability to proliferate abnormally.

Signs and Symptoms

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae).

Common symptoms of chronic or acute leukemia.

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections. Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor. Some patients experience other symptoms, such as feeling sick, having fevers, chills, night sweats, feeling fatigued and other flu-like symptoms. Some patients experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea. If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.

The word leukemia, which means white blood, is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing a harmful imbalance in the blood count. Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.

Causes

No single known cause for any of the different types of leukemia exists. The known causes, which are not generally factors within the control of the average person, account for relatively few cases.  The different leukemias likely have different causes. Leukemia, like other cancers, results from mutations in the DNA. Certain mutations can trigger leukemia by activating oncogenes or deactivating tumor suppressor genes, and thereby disrupting the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances.

Among adults, the known causes are natural and artificial ionizing radiation, a few viruses such as Human T-lymphotropic virus, and some chemicals, notably benzene and alkylating chemotherapy agents for previous malignancies.  Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults.  Cohort and case-control studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia. A few cases of maternal-fetal transmission have been reported.  Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit. Viruses have also been linked to some forms of leukemia. Experiments on mice and other mammals have demonstrated the relevance of retroviruses in leukemia, and human retroviruses have also been identified. The first human retrovirus identified was Human T-lymphotropic virus, or HTLV-1, which is known to cause adult T-cell leukemia.

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies.  The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kind of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers. In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.  For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia.

Whether non-ionizing radiation causes leukemia has been studied for several decades. The International Agency for Research on Cancer expert working group undertook a detailed review of all data on static and extremely low frequency electromagnetic energy, which occurs naturally and in association with the generation, transmission, and use of electrical power.  They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause childhood leukemia. Exposure to significant ELF magnetic fields might result in twofold excess risk for leukemia for children exposed to these high levels of magnetic fields.  However, the report also says that methodological weaknesses and biases in these studies have likely caused the risk to be overstated.  No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated.  Since exposure to such levels of ELFs is relatively uncommon, the World Health Organization concludes that ELF exposure, if later proven to be causative, would account for just 100 to 2400 cases worldwide each year, representing 0.2 to 4.9% of the total incidence of childhood leukemia for that year (about 0.03 to 0.9% of all leukemias).

Diagnosis

Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observations of the symptoms, however, in rare cases blood tests may not show if a patient has leukemia, usually this is because the leukemia is in the early stages or has entered remission. A lymph node biopsy can be performed as well in order to diagnose certain types of leukemia in certain situations.

Following diagnosis, blood chemistry tests can be used to determine the degree of liver and kidney damage or the effects of chemotherapy on the patient. When concerns arise about visible damage due to leukemia, doctors may use an X-ray, MRI, or ultrasound. These can potentially view leukemia's effects on such body parts as bones (X-ray), the brain (MRI), or the kidneys, spleen, and liver (ultrasound). Finally, CT scans are rarely used to check lymph nodes in the chest.

Despite the use of these methods to diagnose whether or not a patient has leukemia, many people have not been diagnosed because many of the symptoms are vague, unspecific, and can refer to other diseases. For this reason, the American Cancer Society predicts that at least one-fifth of the people with leukemia have not yet been diagnosed. Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.  SPRED1 gene mutations can be diagnosed with genetic sequencing.

Treatment

Most forms of leukemia are treated with pharmaceutical medication, typically combined into a multi-drug (chemical cocktail) chemotherapy regimen. Some are also treated with radiation therapy. In some cases, a bone marrow transplant is useful.

Acute Lymphoblastic Leukemia (ALL) Treatment

Management of ALL focuses on control of bone marrow and systemic (whole-body) disease. Additionally, treatment must prevent leukemic cells from spreading to other sites, particularly the central nervous system (CNS) e.g. monthly lumbar punctures. In general, ALL treatment is divided into several phases:

Induction chemotherapy to bring about bone marrow remission. For adults, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment.
Consolidation therapy or intensification therapy to eliminate any remaining leukemia cells. There are many different approaches to consolidation, but it is typically a high-dose, multi-drug treatment that is undertaken for a few months. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). High-risk patients receive higher drug doses of these drugs, plus additional drugs.
CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system in high-risk patients. Standard prophylaxis may include radiation of the head and/or drugs delivered directly into the spine.
Maintenance treatments with chemotherapeutic drugs to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves lower drug doses, and may continue for up to three years.
Alternatively, allogeneic bone marrow transplantation may be appropriate for high-risk or relapsed patients, who may also go through a white blood cell transfer.

Chronic Lymphocytic Leukemia (CLL) Treatment

Decision to treat

Hematologists base CLL treatment on both the stage and symptoms of the individual patient. A large group of CLL patients have low-grade disease, which does not benefit from treatment. Individuals with CLL-related complications or more advanced disease often benefit from treatment. In general, the indications for treatment are:

Falling hemoglobin or platelet count
Progression to a later stage of disease
Painful, disease-related overgrowth of lymph nodes or spleen
An increase in the rate of lymphocyte production

Typical treatment approach

CLL is probably incurable by present treatments. The primary chemotherapeutic plan is combination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The use of a corticosteroid has the additional benefit of suppressing some related autoimmune diseases, such as immunohemolytic anemia or immune-mediated thrombocytopenia. In resistant cases, single-agent treatments with nucleoside drugs such as Fludarabine®, Pentostatin®, or Cladribine® may be successful. Younger patients may consider allogeneic or autologous bone marrow transplantation.

Acute Myelogenous or Myeloid Leukemias (AML) Treatment

Many different anti-cancer drugs are effective for the treatment of AML. Treatments vary somewhat according to the age of the patient and according to the specific subtype of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease, while offering specific treatment for the central nervous system (CNS), if involved. In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission and a lower risk of disease resistance. Consolidation and maintenance treatments are intended to prevent disease recurrence. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

Chronic Myelogenous Leukemia (CML) Treatment

There are many possible treatments for CML, but the standard of care for newly diagnosed patients is Imatinib® (Gleevec®) therapy.  Compared to most anti-cancer drugs, it has relatively few side effects and can be taken orally at home. With this drug, more than 90% of patients will be able to keep the disease in check for at least five years, so that CML becomes a chronic, manageable condition. In a more advanced, uncontrolled state, when the patient cannot tolerate Imatinib®, or if the patient wishes to attempt a permanent cure, then an allogeneic bone marrow transplantation may be performed. This procedure involves high-dose chemotherapy and radiation followed by infusion of bone marrow from a compatible donor. Approximately 30% of patients die from this procedure.

Hairy Cell Leukemia Treatment

Decision to treat

Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/µL), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.

Typical treatment approach

Patients who need treatment usually receive either one week of Cladribine®, given daily by intravenous infusion or a simple injection under the skin, or six months of Pentostatin®, given every four weeks by intravenous infusion. In most cases, one round of treatment will produce a prolonged remission. Other treatments include Rituximab® infusion or self-injection with Interferon-alpha®. In limited cases, the patient may benefit from splenectomy (removal of the spleen). These treatments are not typically given as the first treatment because their success rates are lower than cladribine or pentostatin.

T-cell Prolymphocytic Leukemia Treatment

Most patients with T-cell prolymphocytic leukemia, a rare and aggressive leukemia with a median survival of less than one year, require immediate treatment. T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.  Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin®, fludarabine®, cladribine®), chlorambucil®, and various forms of combination chemotherapy (cyclophosphamide®, doxorubicin®, vincristine®, prednisone CHOP®, cyclophosphamide®, vincristine®, prednisone [COP]®, vincristine®, doxorubicin®, prednisone®, etoposide®, cyclophosphamide®, bleomycin VAPEC-B®). Alemtuzumab® (Campath®), a monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.

Juvenile Myelomonocytic Leukemia Treatment

Treatment for juvenile myelomonocytic leukemia can include splenectomy, chemotherapy, and bone marrow transplantation.

Epidemiology

In 2000, approximately 256,000 children and adults around the world developed a form of leukemia, and 209,000 died from it.  This represents about 3% of the almost seven million deaths due to cancer that year, and about 0.35% of all deaths from any cause.  Of the sixteen separate sites the body compared, leukemia was the 12th most common class of neoplastic disease, and the 11th most common cause of cancer-related death. About 245,000 people in the United States are affected with some form of leukemia, including those that have achieved remission or cure. Approximately 44,270 new cases of leukemia were diagnosed in the year of 2008 in the US.  This represents 2.9% of all cancers (excluding simple basal cell and squamous cell skin cancers) in the United States, and 30.4% of all blood cancers.

Among children with some form of cancer, about a third have a type of leukemia, most commonly acute lymphoblastic leukemia.  A type of leukemia is the second most common form of cancer in infants (under the age of 12 months) and the most common form of cancer in older children.  Boys are somewhat more likely to develop leukemia than girls, and white American children are almost twice as likely to develop leukemia than black American children.  Only about 3% cancer diagnoses among adults are for leukemias, but because cancer is much more common among adults, more than 90% of all leukemias are diagnosed in adults.

History

Leukemia was first observed by pathologist Rudolf Virchow in 1845. Observing an abnormally large number of white blood cells in a blood sample from a patient, Virchow called the condition Leukämie in German, which he formed from the two Greek words leukos (λευκός), meaning "white", and aima (αίμα), meaning "blood". Around ten years after Virchow's findings, pathologist Franz Ernst Christian Neumann found that one deceased leukemia patient's bone marrow was colored "dirty green-yellow" as opposed to the normal red. This finding allowed Neumann to conclude that a bone marrow problem was responsible for the abnormal blood of leukemia patients.

By 1900 leukemia was viewed as a family of diseases as opposed to a single disease. By 1947 Boston pathologist Sydney Farber believed from past experiments that aminopterin, a folic acid mimic, could potentially cure leukemia in children. The majority of the children with ALL who were tested showed signs of improvement in their bone marrow, but none of them were actually cured. This, however, led to further experiments. In 1962, researchers Emil J. Freireich Jr. and Emil Frei III used combination chemotherapy to attempt to cure leukemia. The tests were successful with some patients surviving long after the tests.

Research

Significant research into the causes, prevalence, diagnosis, treatment, and prognosis of leukemia is being performed. Hundreds of clinical trials are being planned or conducted at any given time. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures. In general, there are two types of leukemia research: clinical/translational research and basic science research. Clinical/translational research focuses on studying the disease in a defined and generally immediately patient-applicable way, whereas basic science research studies the disease process at a distance and the results from such studies are generally less immediately useful to patients with the disease. Treatment through gene therapy is currently being pursued. One such approach turns T-cells into cancer-targeting attackers. As of August 2011, a year after treatment, two of the three patients are cancer-free.

Society and Culture

Leukemias are often romanticized in 20th century fiction. It is presented as a pure, clean disease, whose innocent, beautiful, and spiritually sensitive victims tragically die young. As such, it is the cultural successor to tuberculosis.

In Pregnancy

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women.  How it is handled depends primarily on the type of leukemia. Nearly all leukemias appearing in pregnant women are acute leukemias.  Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.  Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones.  Treatment for chronic lymphocytic leukemias, which are rare in pregnant women, can often be postponed until after the end of the pregnancy.

External Links

Hematology Atlas
Leukemia at the Open Directory Project
Clinically reviewed leukaemia information for patients, from Cancer Research UK
UK leukaemia statistics from Cancer Research UK
Gale Group

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Vestibular Schwannoma (Auditory tumor)

2012-02-20T10:20:00.000-08:00

Vestibular schwannoma, also called acoustic neuroma, and occasionally acoustic neurilemmoma, acoustic neurinoma, and auditory tumor is a benign (non cancerous) primary intracranial tumor of the myelin-forming cells of the vestibulocochlear nerve (CN VIII) - the nerve that connects the ear to the brain. The tumor usually grows slowly. As it grows, it presses against the hearing and balance nerves. At first, you may have no symptoms or mild symptoms. They can include:

Loss of hearing on one side
Ringing in ears
Dizziness and balance problems

A vestibular schwannoma can be difficult to diagnose, because the symptoms are similar to those of middle ear problems. Ear exams, hearing tests and scans can show if you have it. If the tumor stays small, you may only need to have it checked regularly. If you do need treatment, surgery and radiation are options. If the tumors affect both hearing nerves, it is often because of a genetic disorder called neurofibromatosis. The tumor can also eventually cause numbness or paralysis of the face. If it grows large enough, it can press against the brain, becoming life-threatening.

The term "vestibular schwannoma" involves the vestibular portion of the 8th cranial nerve and arises from Schwann cells, which are responsible for the myelin sheath in the peripheral nervous system. Approximately 3,000 cases are diagnosed each year in the United States with a prevalence of about 1 in 100,000 worldwide. It comprises 5-10% of all intracranial neoplasms in adults. Incidence peaks in the fifth and sixth decades and both sexes are affected equally.

The term acoustic is a misnomer, as the tumor rarely arises from the acoustic (or cochlear) division of the vestibulocochlear nerve. The term neuroma is also a misnomer, since it means "nerve tumor" but an acoustic neuroma is a schwannoma.

Signs and Symptoms

The earliest symptoms of vestibular schwannomas include ipsilateral sensorineural hearing loss/deafness, disturbed sense of balance and altered gait, vertigo with associated nausea and vomiting, and pressure in the ear, all of which can be attributed to the disruption of normal vestibulocochlear nerve function. Additionally more than 80% of patients have reported tinnitus (most often a unilateral high-pitched ringing, sometimes a machinery-like roaring or hissing sound, like a steam kettle).

Large tumors that compress the adjacent brainstem may affect other local cranial nerves. Paradoxically, the 7th cranial nerves are rarely involved pre-operatively; involvement of the trigeminal nerve (CN V) may lead to loss of sensation in the involved side's face and mouth. The glossopharyngeal and vagus nerves are uncommonly involved, but their involvement may lead to altered gag or swallowing reflexes. Larger tumors may lead to increased intracranial pressure, with its associated symptoms such as headache, vomiting, and altered consciousness.

Hearing Loss

Patients with a severe or profound unilateral hearing loss following the removal of an acoustic neuroma tumour are significantly disabled in a number of situations such as hearing sounds from the deaf side, hearing in the presence of background noise (both in quiet and noisy surroundings) and localising sounds.

The perceived hearing handicap may even be greater in unilateral losses than in bilateral. It has also been reported that patients with unilateral hearing loss experience difficulties in group discussions and dynamic listening situations where there is limited possibility to compensate for the handicap by changing listening position. It is recommended that the hearing difficulties after tumour removal should be thoroughly examined with each patient and rehabilitative options discussed.

Pathogenesis

Vestibular schwannomas may occur sporadically (meaning the cause is unknown), or in some cases occur as part of von Recklinghausen neurofibromatosis, in which case the neuroma may take on one of two forms.

In Neurofibromatosis type I, a schwannoma may sporadically involve the 8th nerve, usually in adult life, but may involve any other cranial nerve or the spinal root. Bilateral acoustic neuromas are rare in this type.
In Neurofibromatosis type II, bilateral acoustic neuromas are the hallmark and typically present before the age of 21. These tumors tend to involve the entire extent of the nerve and show a strong autosomal dominant inheritance. Incidence is about 5 to 10%.

The usual tumor in the adult presents as a solitary tumor, originating in the nerve. It usually arises from the vestibular portion of the 8th nerve, just within the internal auditory canal. As the tumor grows, it usually extends into the posterior fossa to occupy the angle between the cerebellum and the pons (cerebellopontine angle). Because of its position, it may also compress the 5th, 7th, and less often, the 9th and 10th cranial nerves. Later, it may compress the pons and lateral medulla, causing obstruction of the cerebrospinal fluid and increased intracranial pressure. Schwannomas can occur in relation to other cranial nerves or spinal nerve roots, resulting in radiculopathy or spinal cord compression. Trigeminal neuromas are the second most common form of schwannomas involving cranial nerves. Schwannomas of other cranial nerves are very rare.

Diagnosis

Contrast-enhanced CT scans will detect almost all vestibular schwannomas that are greater than 2.0 cm in diameter and project further than 1.5 cm into the cerebellopontine angle. Those tumors that are smaller may be detected by MRI with gadolinium enhancement. Audiology and vestibular tests should be concurrently evaluated using air conduction and bone conduction threshold testing to assess for sensorineural versus conduction hearing loss.

Vestibular schwannoma (Acoustic neuroma)

CNS: NEUROFIBROMATOSIS 2 Bilateral schwannomas are readily apparent in this patient. The schwannoma on the left is encased by a plaque-like meningioma. Image and description are from the AFIP Atlas of Tumor Pathology, according to entry # 406140 in Pathology Education Instructional Resource.

Treatment

Indicated treatments for schwannomas include surgical removal and radiotherapy. About 25% of all vestibular schwannomas are treated with medical management consisting of a periodic monitoring of the patient's neurological status, serial imaging studies, and the use of hearing aids when appropriate.

Conservative Treatment

Because these neuromata grow so slowly, a physician may opt for conservative treatment beginning with an observation period. In such a case, the tumor is monitored by annual MRI to monitor growth. This route is common among patients over 70 years old. Records suggest that about 45% of acoustic neuromata do not grow detectably over the 3-5 years of observation. In rare cases, acoustical neuromata have been known to shrink spontaneously. Often people with acoustic neuromata die of other causes before the neuroma becomes life-threatening. This is especially true of elderly people possessing a small neuroma. Since the growth rate of an acoustic neuroma rarely accelerates, annual observation is sufficient. Vestibular schwannoma may cause either gradual or, less commonly, sudden hearing loss and tinnitus.

Surgery

Removal of schwannomas may be performed using several approaches. Each approach has its advantages and disadvantages. Microsurgery for vestibular schwannoma is the only technique that removes the tumor. Radiation treatment (discussed in another section) does not remove the tumor, but has the potential to slow or stop its growth. Surgery is the only treatment that will definitively treat balance symptoms associated with tumor growth, as the vestibular nerves are removed at surgery. Surgery cannot repair damage that has already occurred to the facial or hearing nerves. Even after surgery, there is a small chance that the neuroma will grow back and follow-up MRI scans are necessary.

Choice of surgical approach is based on the patient's age, medical condition, size of tumor, and preoperative hearing thresholds and speech discrimination, as well as other tests such as electronystagmography, imaging, and auditory brainstem response testing. The patient's and surgeon's preferences also play a significant role.

During removal of the tumor, the tumor along with the superior and inferior vestibular nerves are removed. This results in an acute loss of vestibular input to the brain from the operated side. However, vestibular function improves rapidly due to compensation by the other ear and other balance mechanisms. Surgery carries risk to the facial nerve which may therefore be monitored during the procedure. Best results (normal or near normal facial function) are more likely with small neuromas.

Three surgical approaches are commonly used. The first is the translabyrinthine approach, which destroys hearing in the affected ear. Thus, it is often employed in patients who already have poor speech discrimination in the affected ear. Any size tumor may be removed with this approach. There is no brain retraction with this approach, so it is often considered the safest route to remove the tumor. In patients with neurofibromatosis type 2 who undergo auditory brainstem implantation, this technique is used as it provides the most direct path of access to the lateral recess and cochlear nucleus, where the device is placed.

The two other approaches (suboccipital retrosigmoid and middle fossa) are hearing preservation approaches, which have a chance of preserving some or all of the hearing in the affected ear. Neurosurgeons often prefer the retrosigmoid approach, as they are frequently more familiar with it from training.

The middle fossa approach is used for tumors typically less than 2 cm in greatest dimension, where hearing conservation is to be attempted. This approach has the advantage over the retrosigmoid approach in its direct access to the lateral end of the internal auditory canal. Multiple reports have shown that the retrosigmoid approach cannot reach the lateral end of the internal auditory canal without violating the posterior semicircular canal, and hence destroying the hearing.

A less common approach is minimally invasive endoscopic surgery. This approach is available in specialized centers. Schwannoma surgery is highly technically demanding. It may be performed by neurosurgeons or otolaryngologists, alone or together.

Radiation Therapy

Radiation therapy is done in a variety of ways, but mainly by four methods:

CyberKnife,
Gamma knife radiosurgeryFractionated stereotactic radiotherapy, with a linear accelerator (linac), or
Proton therapy.

In the gamma knife approach, 201 beams of gamma radiation are focused on the tumor in a single session. The damage to the tumor at the convergence point may cause it to stop growing but usually does not cause it to shrink in the long term. It may cause short-term shrinkage due to necrosis in the tumor. The damage may be to the tumor cells and/or to the tumor vasculature.

It is not clear what percentage of tumors are controlled by this method for long periods. In earlier times when higher radiation doses were used, the failure rate was about 12% (which then required surgery). Most surgeons feel that these tumors are much more difficult to remove after radiation treatment. Radiation does not remove the tumor, and when irradiated tumors are surgically removed, it is often found that they have growing tumor cells in them.

Two risks of radiation treatment are carcinogenic progression of the acoustic neuroma (conversion from benign to malignant) or induction of other tumors (such as glioblastoma) in the nearby irradiated brain tissue. The incidence of these events appears to be low, and it is often said to be one in one thousand or less (however, the incidence is markedly higher in patients with neurofibromatosis Type 2). This calculation is done by dividing the number of obvious cases of tumorigenic progression or secondary tumor reported in the medical literature by the estimated number of gamma knife procedures done in the world to date. This is not a scientifically valid method of estimating the carcinogenic risk of medical radiation exposures, and involves a list of very questionable assumptions. The proper and scientifically valid way to estimate such risks can be found at the web site of the Health Physics Society (see External Links below), where estimates of the risks of CT scans and other procedures can be found. These calculations have never been made for gamma knife radiosurgery.

Due to the possibility of regrowth and the possibility of tumorigenic progression or secondary tumors, it is essential that radiation treatments for schwannomas be followed by yearly MRI for the rest of the patient's life. As of 2007 the cost of an MRI was between $1,500-$3,000. Long-term secondary effects (for instance cognitive effects) on a scale of 10-20 years are not yet established for gamma knife surgery.

Fractionated stereotactic therapy involves a beam of ionizing radiation focused on the tumor from a moving gantry. The beam is wider and less accurate than that of the gamma knife. The total dose is also much higher than that used in gamma knife radiosurgery, but the fractionation of the dose (done on many different days) spares normal tissue. This method has not been done on as many patients as gamma knife procedures and there have not been as many years of follow-up study. This means that the tumor control by this method is not yet established, and the incidence of secondary effects of the radiation are not yet known. There are a number of variations on the linac machine, which can confuse patients. The best known are the "Peacock" which is essentially a modified collimator, and the Cyberknife which uses a miniature linac machine attached to a robot arm which is guided using x-ray imaging to check the position of the patient between each treatment shot.

A proton therapy machine uses a beam of protons to kill the tumour and a cyclotron is used to generate the beam. This is preferable to the x-rays used by the linac and gamma knife machines as the protons can be stopped before they exit the tumor, thus reducing damage to normal tissue.

External Links

"Hearing Disorders - Acoustic Neuromas: Causes of Acoustic Neuroma". House Ear Clinic.
Acoustic Neuroma – Diagnosis and Treatment - UPMC, Pittsburgh, PA, USA
Acoustic Neuroma - at American Hearing Research Foundation, Chicago, IL, USA
Acoustic Neuroma New York
Acoustic neuroma radiation treatment options
MR and CT scans Schwannoma Image Database
Health Physics Society

References

McLeod B, Upfold L, Taylor A. Self reported hearing difficulties following excision of vestibular schwannoma. International journal of audiology. 2008 Jul;47(7):420-30.
Andersen HT, Schrøder SA, Bonding P. Unilateral deafness after acoustic neuroma surgery: subjective hearing handicap and the effect of the bone-anchored hearing aid. Otology and neurotology. 2006 Sep;27(6):809-14.
Noble W, Gatehouse S. Interaural asymmetry of hearing loss, Speech, Spatial and Qualities of Hearing Scale (SSQ) disabilities, and handicap. International journal of audiology. 2004; 43(2): 100–14.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

Phantom Pain

2012-02-19T10:32:00.000-08:00

Phantom pain sensations are described as perceptions that an individual experiences relating to a limb or an organ that is not physically part of the body. Limb loss is a result of either removal by amputation or congenital limb deficiency. However, phantom limb sensations can also occur following nerve avulsion or spinal cord injury. Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast or an internal organ. Phantom limb pain is the feeling of pain in an absent limb or a portion of a limb. The pain sensation varies from individual to individual.

Phantom limb sensation is the term given to any sensory phenomenon (except pain) which is felt at an absent limb or a portion of the limb. It has been known that at least 80% of amputees experience phantom sensations at some time of their lives. Some experience some level of this phantom pain and feeling in the missing limb for the rest of their lives.

There are various types of sensations that may be felt:

Sensations related to the phantom limb's posture, length and volume e.g. feeling that the phantom limb is behaving just like a normal limb like sitting with the knee bent or feeling that the phantom limb is as heavy as the other limb. Sometimes, an amputee will experience a sensation called telescoping. This is the feeling that the phantom limb is gradually shortening over time.
Sensations of movement (e.g. feeling that the phantom foot is moving).
Sensations of touch, temperature, pressure and itchiness. Many amputees report of feeling heat, tingling, itchiness and pain.

The term “phantom limb” was first coined by American neurologist Silas Weir Mitchell in 1871. Mitchell described that “thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them”. However, in 1551, French military surgeon Ambroise Paré recorded the first documentation of phantom limb pain when he reported that, “For the patients, long after the amputation is made, say that they still feel pain in the amputated part”.

I placed a coffee cup in front of John and asked him to grab it [with his phantom limb]. Just as he said he was reaching out, I yanked the cup away.

"Ow!" he yelled. "Don't do that!"

"What's the matter?"

"Don't do that", he repeated. "I had just got my fingers around the cup handle when you pulled it. That really hurts!"

Hold on a minute. I wrench a real cup from phantom fingers and the person yells, ouch! The fingers were illusory, but the pain was real - indeed, so intense that I dared not repeat the experiment.
-Ramachandran, Phantoms in the Brain, p. 43.

Signs and Symptoms - Phantom pain involves the sensation of pain in a part of the body that has been removed.

Epidemiology

Phantom limb pain and phantom limb sensations are linked, but must be differentiated from one another. While phantom limb sensations are experienced by those with congenital limb deficiency, spinal cord injury, and amputation, phantom limb pain occurs almost exclusively as a result of amputation. Almost immediately following the amputation of a limb, 90-98% of patients report experiencing a phantom sensation. Nearly 75% of individuals experience the phantom as soon as anesthesia wears off, and the remaining 25% of patients experience phantoms within a few days or weeks. Of those experiencing innocuous sensations, a majority of patients also report distinct painful sensations.

The prevalence of phantom limb pain differs based on the location of the amputation. The prevalence of phantom pain in upper limb amputees is nearly 82%, while the prevalence of pain in lower limb amputees is only 54%. Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain.

Pathophysiology

The neurological basis and mechanisms for phantom limb pain are all derived from experimental theories and observations. Little is known about the true mechanism causing phantom pains, and many theories highly overlap. Historically, phantom pains were thought to originate from neuromas located at the stump tip. Traumatic neuromas, or non-tumor nerve injuries, often arise from surgeries and result from the abnormal growth of injured nerve fibers. Although stump neuromas contribute to phantom pains, they are not the sole cause. This is because patients with congenital limb deficiency can sometimes, although rarely, experience phantom pains. This suggests that there is a central representation of the limb responsible for painful sensations. Currently, theories are based on altered neurological pathways and cortical reorganization. Although they are highly intertwined, mechanisms are often separated into peripheral, spinal, and central mechanisms.

Peripheral Mechanisms

Neuromas formed from injured nerve endings at the stump site are able to fire abnormal action potentials, and were historically thought to be the main cause of phantom limb pain. Although neuromas are able to contribute to phantom pain, pain is not completely eliminated when peripheral nerves are treated with conduction blocking agents. Physical stimulation of neuromas can increase C fiber activity, thus increasing phantom pain, but pain still persists once the neuromas have ceased firing action potentials. The peripheral nervous system is thought to have at most a modulation effect on phantom limb pain.

Spinal Mechanisms

In addition to peripheral mechanisms, spinal mechanisms are thought to have an influencing role in phantom pains. Peripheral nerve injury can lead to the degeneration of C fibers in the dorsal horn of the spinal cord, and terminating A fibers may subsequently branch into the same lamina. If this occurs, A fiber inputs could be reported as noxious stimuli. Substance P, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers. This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains.

Central Mechanisms and Cortical Remapping

Under ordinary circumstances, the genetically determined circuitry in the brain remains largely stable throughout life. It was thought, until about 30 years ago, that no new neural circuits could be formed in the adult mammalian brain. Recently, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping. The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex to the ipsilateral cortex. In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements. It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred. Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation. There are Multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent.

The Neuromatrix Theory

The neuromatrix theory proposes that there is an extensive network connecting the thalamus and the cortex, and the cortex and the limbic system. It is a theory that extends beyond body schema theory and incorporates the conscious awareness of oneself. This theory proposes that conscious awareness and the perception of self are generated in the brain via patterns of input that can be modified by different perceptual inputs. The network is genetically predetermined, and is modified throughout one’s lifetime by various sensory inputs to create a neurosignature. It is the neurosignature of a specific body part that determines how it is consciously perceived. The input systems contributing to the neurosignature are primarily the somatosensory, limbic, and thalamocortical systems. The neuromatrix theory aims to explain how certain activities associated with pain lead to the conscious perception of phantom pain. The persistence of the neurosignature, even after limb amputation, may be the cause of phantom sensations and pain. Phantom pain may arise from abnormal reorganization in the neuromatrix to a pre-existing pain state.

Opposition to the neuromatrix theory exists largely because it fails to explain why relief from phantom sensations rarely eliminates phantom pains. It also does not address how sensations can spontaneously end and how some amputees do not experience phantom sensations at all. In addition, a major limitation of the neuromatrix theory is that it too broadly accounts for various aspects of phantom limb perception. It is also likely that it is too difficult to be tested empirically, especially when testing painless phantom sensations.

Management

Various methods have been used to treat phantom limb pain. Doctors may prescribe medications to reduce the pain. Some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain. Often physical methods such as light massage, electrical stimulation, and hot and cold therapy have been used with variable results. There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore ineffective. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate less than 30%. It is important to note that this rate of success does not exceed the placebo effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception.

Nonsurgical Techniques: Mirror Box Therapy

Mirror box therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb. Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible. This theory proposes that the phantom limb feels paralyzed because there is no feedback from the phantom back to the brain to inform it otherwise. Ramachandran and Rogers-Ramachandran believed that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed.

A diagrammatic explanation of the mirror box. The patient places the good limb into one side of the box and the amputated limb into the other side. Due to the mirror, the patient sees a reflection of the good hand where the missing limb would be. The patient thus receives artificial visual feedback that the "resurrected" limb is now moving when they move the good hand.

Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. In a 2010 study of phantom limb pain, Martin Diers and his colleagues found that "In a randomized controlled trial that used graded motor imagery...and mirror training, patients with complex regional pain syndrome or phantom limb pain showed a decrease in pain as well as an improvement in function post-treatment and at the 6-month follow-up. And it was shown that the order of treatment mattered." This study found that mirrored imagery produced no significant cortical activity in patients with phantom limb pain and concluded that "The optimal method to alter pain and brain representation, and the brain mechanisms underlying the effects [of] mirror training or motor imagery, are still unclear". A number of small scale research studies have shown encouraging results, however there is no current consensus as to the effectiveness of mirror therapy. Recent reviews of the published research literature by Mosely and Ezendam concluded that much of the evidence supporting mirror therapy is anecdotal or comes from studies that had weak methodological quality. In 2011 a large scale review of the literature on mirror therapy by Rothgangel summarized the current research as follows.

"For stroke there is a moderate quality of evidence that MT [Mirror Therapy] as an additional intervention improves recovery of arm function, and a low quality of evidence regarding lower limb function and pain after stroke. The quality of evidence in patients with complex regional pain syndrome and phantom limb pain is also low. Firm conclusions could not be drawn. Little is known about which patients are likely to benefit most from MT, and how MT should preferably be applied. Future studies with clear descriptions of intervention protocols should focus on standardized outcome measures and systematically register adverse effects"

Mirror Box Therapy with David Butler

Pharmacological Treatment

Pharmacological techniques are often continued in conjunction with other treatment options. Doses or pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptyline, and sodium channel blockers, mainly carbamazepine, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine, calcitonin, and lidocaine.

Surgical Techniques: Deep-brain stimulation

Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. Prior to surgery, patients undergo functional brain imaging techniques such as PET scans and functional MRI to determine an appropriate trajectory of where pain is originating. Surgery is then carried out under local anesthetic, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode with four contact points was placed on the brain. Once the electrode was in place, the contact locations were altered slightly according to where the patient felt the greatest relief from pain. Once the location of maximal relief was determined, the electrode was implanted and secured to the skull. After the primary surgery, a secondary surgery under general anesthesia was conducted. A subcutaneous pulse generator was implanted into a pectoral pocket below the clavicle to stimulate the electrode. It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished.

External links

V.S. Ramachandran's website
Ramachandran and Brang. 2009. Phantom touch. Scholarpedia.org
Phantom Limb Research in the UK
WNYC - Radio Lab: Where Am I? (May 05, 2006) downloadable segment of radio program looks at historical examples and a present-day case of phantom limbs
Ramachandran's Reith Lecture on Phantom Limbs
Amputee Coalition of America (ACA) - National Limb Loss Information Center
Review article from the Science Creative Quarterly
End The Pain Project dedicated to global reduction of phantom limb pain for amputees

References

Halligan, Peter W. (2002), "Phantom limbs: The body in mind", Cognitive Neuropsychiatry 7 (3): 251–268, doi:10.1080/13546800244000111, PMID 16571541.
Bittar, Richard G.; Otero, Sofia; Carter, Helen; Aziz, Tipu Z. (May 2005), "Deep Brain Stimulation for Phantom Limb Pain", Journal of Clinical Neuroscience 12 (4): 399–404, doi:10.1016/j.jocn.2004.07.013, PMID 15925769.
Cruz, Vitor Tedim; Nunes, Belina; Reis, Ana Mafalda; Pereira, Jorge Resende (2005), "Cortical Remapping in Amputees and Dysmelic Patients: A Functional MRI Study", NeuroRehabilitation 18 (1): 299–305.
Diers, M.; Christmann, C.; Koeppe, C.; Ruf, M.; Flor, H. (2010), "Mirrored, imagined, and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain", Pain 149 (2): 296–304.
Ezendam, Danielle; Bongers, Raoul; Jannink, Michel (2009), "Systematic review of the effectiveness of mirror therapy in upper extremity function", Disability Rehabilitation 20 (May): 1–15.
Giummarra, Melita J.; Gibson, Stephen J.; Georgiou-Karistianis, Nellie; Bradshaw, John L. (April 2007), "Central Mechanisms in Phantom Limb Perception: The Past, Present, and Future", Brain Research Reviews 54 (1): 219–232, doi:10.1016/j.brainresrev.2007.01.009, PMID 17500095.
Karl, Anke; Birbaumer, Niels; Lutzenberger, Werner; Cohen, Leonardo G.; Flor, Herta (May 2001), "Reorganization of Motor and Somatosensory Cortex in Upper Extremity Amputees with Phantom Limb Pain", The Journal of Neuroscience 21 (10): 3609–3618, PMID 11331390.
Kooijman, Carolien M.; Dijkstra, Pieter U.; Geertzen, Jan H. B.; Elzinga, Albert; van der Schans, Cees P. (July 2000), "Phantom Pain and Phantom Sensations in Upper Limb Amputees: An Epidemiological Study", Pain 87 (1): 33–41, doi:10.1016/S0304-3959(00)00264-5, PMID 10863043.
MacLachlan, Malcolm; McDonald, Dympna; Waloch, Justine (2004), "Mirror Treatment of Lower Limb Phantom Pain: A Case Study", Disability and Rehabilitation 26 (14/15): 901–904, doi:10.1080/09638280410001708913, PMID 15497919.
Moseley, G.; Gallace, A.; Spence, C. (2008), "Is mirror therapy all it is cracked up to be? Current evidence and future directions", PAIN 138 (1): 7–10.
Melzack, R (1992), "Phantom Limbs", Scientific American 266 (4): 120–126, doi:10.1038/scientificamerican0492-120, PMID 1566028.
Ramachandran, V. S.; Hirstein, William (2008), "The Perception of Phantom Limbs: The D. O. Hebb Lecture", Brain 121 (1): 1603–1630, doi:10.1093/brain/121.9.1603, PMID 9762952.
Ramachandran, V. S.; Rogers-Ramachandran, D. (April 1996), "Synaesthesia in Phantom Limbs Induced with Mirrors", Proceedings of the Royal Society of London B-Biological Sciences 263 (1369): 377–386, doi:10.1098/rspb.1996.0058, PMID 8637922.
Richardson, Cliff; Glenn, Sheila; Horgan, Maureen; Nurmikko, Turo (October 2007), "A Prospective Study of Factors Associated with the Presence of Phantom Limb Pain Six Months After Major Lower Limb Amputation in Patients with Peripheral Vascular Disease", The Journal of Pain 8 (10): 793–801, doi:10.1016/j.jpain.2007.05.007, PMID 17631056.
Rothgangel, A.; Braum, S.; Beurskens, A.; Seitz, R.; Wade, D. (2011), "The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature", International Journal of Rehabilitation Research 34 (March): 1–13.

Content is in the public domain and may be reprinted, except if marked as copyrighted (©). Please credit Holistic Lifestyle Community Blog as the source. All copyrighted material is the property of its respective owners and may not be reprinted without their permission.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM) and its therapies and what may be best for your overall health with a licensed health care provider (i.e. physician, registered dietician, pharmacist, etc.). The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.