AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Amanita muscaria, also called fly agaric or soma, and Amanita pantherina, also called panther or panther amanita, are representative of the mushrooms in the ibotenic acid and muscimol mushroom group that produce ethanol-like intoxication and jerking movements. The genus name (Amanita) and species name (muscaria) can be confusing because the names imply a type of toxin, whereas the true toxins might not be obvious.

The toxin muscarine, which was first extracted from A muscaria in 1869, is not the major toxin in A muscaria. Ibotenic acid and muscimol are the major toxins in this mushroom. These substances are psychoactive, inducing a state of intoxication similar to that induced by ethanol, with a mix of excitation, sedation, and mild hallucinations. Although this mushroom is in the genus Amanita, it does not contain amatoxin, which is responsible for the serious and life-threatening nature of cyclopeptide-type mushroom poisoning.

The 8 general types of mushrooms that can cause poisoning are as follows:

1. Cyclopeptide (eg, Amanita phalloides) and cyclopeptide and/or orellanine (Cortinarius mushrooms)
2. Ibotenic acid and/or muscimol (A muscaria, A pantherina)
3. Gyromitrin, or monomethylhydrazine (genus Gyromitra)
4. Muscarine (Inocybe and Clitocybe mushrooms)
5. Coprine (Coprinus atramentarius) (ie, inky cap)
6. Psilocybin (Psilocybe and Paneolus mushrooms, magic mushrooms)
7. GI irritant mushrooms
8. Miscellaneous

A classification of 14 syndromic categories of mushroom poisoning has been proposed. It improves the definition of the miscellaneous category, but this classification system has yet to be widely adopted.^{1, 2}

Mushrooms in the ibotenic acid group are commonly found throughout the United States, Europe, and Asia. They are found in wooded areas, especially among conifer forests, in the spring and fall seasons of North America. The young specimens emerge from their egg, with patches of membrane left covering the cap and forming a cup (volva) at the base. The mature specimens often have brilliant cap colors and delicate skirts and cups and are substantial enough to be tempting (unlike the pretty but small waxy caps). Many everyday representations of mushrooms depict the A muscaria because of its shape and bright coloring.

Mushroom poisoning in children is an infrequent but perennial problem for parents and healthcare workers. Parental anxiety is generally high because of their fears of the major untoward effects. Healthcare workers are challenged to identify such poisoning, to discern whether intoxication has taken place, to order appropriate diagnostic studies, and to prescribe reasonable therapy. The varied nature of mushroom toxicities, the variety of the ubiquitous fungi, and the relative infrequency of the ingestions make the task difficult. Dried mushrooms have been promoted on the Internet because of their various properties, and their ingestion might lead to serious toxicity from the mushroom or from unknown adulterants added to them.³

Various cultures throughout the world have used fungi for ceremonies and for divinatory purposes, practices that date back 3000 years. In North America, the Algonquin people used A muscaria for religious and ritualistic ceremonies. In some European and Asian cultures, the urine of a person or a deer ingesting these mushrooms is consumed to achieve secondary intoxication.

Pathophysiology

A muscaria and A pantherina contain ibotenic acid, muscimol, and muscazone. These isoxazole derivatives are present in various concentrations depending on the environmental conditions, the maturity of the fungus, and the season of the year. Ibotenic acid and muscimol are relatively stable; for instance, toxic activity has been maintained in dried plants for as long as 7 years. Other toxins are likely present in these mushrooms because pure extracts of ibotenic acid or muscimol do not account for all of the symptoms observed after their ingestion.⁴ Ibotenic acid resembles glutamic acid, and, in animals, it acts on glutaminergic receptors to produce excitatory effects. Muscimol, formed by decarboxylation of ibotenic acid, is similar to gamma-aminobutyric acid (GABA). Both of these chemicals can cross the blood-brain barrier.⁴

Demonstrating high affinity for GABA receptors, muscimol activates GABA receptors and, thereby, can act as a sedative. Many of the CNS effects of muscimol are ascribed to its ability to act as a GABA agonist. By comparison, ibotenic acid is more of a CNS stimulant, acting on glutamic acid receptors. In humans, most of the ibotenic acid ingested is excreted unchanged in the urine. Some ibotenic acid is metabolized to muscimol. About one third of the amount of muscimol ingested is excreted unchanged, one third is conjugated, and the rest is oxidized.

Frequency

United States

In 2005, 7146 mushroom ingestions were reported to the Poisoning Exposure Database of the American Association of Poison Control Centers (AAPCC).⁵ About 81% of cases involved mushrooms of unknown type. Mushrooms containing ibotenic acid accounted for 36 cases, with 11% involving children younger than 6 years. About 50% of all cases involving ibotenic acid mushrooms were intentional ingestions, and 86% were treated at a healthcare facility. One death was attributed to ibotenic acid mushrooms in 2004, whereas no deaths were reported in the preceding 5 years or subsequent 1 year of data collection. The manner of confirming A muscaria involvement in this fatality was not described, and the fact that it was purchased on the Internet raises questions about the integrity of the contents.³

International

The incidence of all types of toxic mushroom poisonings, including those from the ibotenic acid group, appears to be increasing in Europe and Asia. Estimates of the actual incidence are not available.^{1, 2}

Mortality/Morbidity

Fatalities from mushrooms are rare, but they do occur.

• From 1999-2005, 26 deaths due to mushrooms were reported to the US Poison Control Center, and one death was attributed to mushrooms containing ibotenic acid.³ That death in 2004 involved a 44-year-old man who ate 6-10 freeze-dried mushrooms, purported to be A muscaria, which he obtained from the Internet. Paramedics found him in cardiac arrest, and he eventually died 10 days later with anoxic brain injury. Whether the mushroom was confirmed to be A muscaria was not mentioned.
• In 2005, poison control centers reported 42% of cases had no or minor effects, 39% had moderate effects, 3% suffered severe effects, and the outcome was unknown in 16%.⁵
• Most toxic effects of mushrooms containing ibotenic acid are temporary, lasting 2-6 hours to 2 days.
• In Slovenia, a 48-year-old man consumed several A muscaria mushrooms and, within 30 minutes, developed vomiting and lethargy.⁶ He was found comatose, having a seizurelike episode. He awoke and was oriented 10 hours after ingestion. His condition deteriorated 18 hours after ingestion, and he became confused and uncooperative. Paranoid psychosis with visual and auditory hallucinations appeared, persisted for 5 days, and resolved with short-term drug therapy without later recurrence.
• Descriptions of cases reported to the North American Mycological Association, toxicology section, illustrate the typical course of many mushroom poisonings; however, these were not necessarily confirmed by health care professionals.⁷

Age

Adults are frequently involved as foragers for morels. Because of errors in identification, they may ingest toxin-containing look-alike mushrooms. Adults may also be inadvertently poisoned when they consume mushrooms, picked from the ground or purchased dried, to achieve intoxication.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Query the patient about how many mushrooms were consumed, how they were prepared, and when the mushrooms were eaten. The concentration of psychoactive substances is low in any one plant, and, in general, about 6 or more plants must be ingested to produce toxic symptoms. However, the effects of mushrooms vary. An amount as small as a mouthful can cause symptoms.

• Obtain a history of the exposure that includes the following:
• • Quantity of mushrooms ingested
  • Preparation of the mushroom (eg, raw, cooked)
  • Time of the ingestion
  • Symptoms and their time of onset after ingestion
  • Treatment before the patient's arrival, including home remedies
  • Medications regularly taken and any coingestants
• The timing of symptom onset is a crucial element of the history in differentiating life-threatening mushroom poisonings from those involving the cyclopeptide group (including A phalloides, which causes symptoms within 6-24 h of ingestion) and from those that typically have an onset of symptoms within 6 hours of ingestion (eg, mushrooms of the ibotenic acid group).^{1, 2, 8, 9}
• Identification of the actual mushroom consumed is important but is typically impossible because the mushroom in question has already been digested.
• • A muscaria has a scarlet cap, is 5-30 cm in diameter, and contains white warts. The stalk is white, is frequently hollow, and is often as long as 15-20 cm. A prominent cup (volva) is found at the bottom of the stalk, with numerous rings superiorly. The gills of A muscaria are free and white. The spores are also white. Its appearance can vary depending on the geographic location. The scarlet cap is predominantly found in western North America. Caps that are orange to yellow-orange caps are most frequent in eastern North America.
  • A muscaria can occur alone or in groups on the ground of forests, in grassy areas and lawns, and especially under trees.
  • Different types of mushrooms can be found in the same location, and a single sample can lead to false identification of the mushroom that was ingested. Considering all possible mushrooms in the immediate vicinity of where the ingestion occurred is wise.
  • When no specimen is brought in with a patient with a suspected mushroom ingestion, sending an experienced forager to the site to collect any mushrooms growing in the area might be helpful.
  • When mushrooms are obtained for identification, the entire mushroom should be dug up to preserve the architecture of the bulb, stem, and cap. Place individual mushrooms in a dry paper bag, not a plastic or cloth bag. Transporting the mushrooms in a careful, dry manner minimizes destruction of the natural architecture of the mushrooms, discoloration of the cap or gills, and premature release of the spores. Do not refrigerate or crush the mushrooms.
  • Collecting the patient's gastric contents by means of gastric lavage or after emesis might yield identifiable spores.
  • Remote viewing by digital photography and Internet transmission may aid the identification of unknown mushrooms by mycologists.¹⁰

Physical

Once ingested, A muscaria produces symptoms within 30-90 minutes. Peak effects have been noted at 2-3 hours. The initial symptom is drowsiness, followed by confusion, ataxia, dizziness, euphoria, and intoxication. These symptoms can proceed to hyperkinesis, muscle jerks, spasms, and delirium. Deep sleep or coma can occur and generally lasts 4-8 hours. If symptoms such as vomiting, diarrhea, and abdominal pain begin 6 hours or more after ingestion, poisoning with the potentially life-threatening cyclopeptide mushrooms (eg, A phalloides) should be considered.

• Vital signs: Pulse and blood pressure are usually unchanged.
• Respiration: Breathing is slow and regular, similar to that in deep sleep.
• GI: GI upset and vomiting occur but are not common. When vomiting or diarrhea does occur, fluid and electrolyte changes are uncommon.
• Integumentary: Skin may be reddened and warm to the touch.
• Musculoskeletal: Muscle spasms may occur.
• Neurologic: Agitation and CNS depression may occur.
• • Especially in children, tonic-clonic seizures, fasciculations, and myoclonic jerking lasting 6-9 hours may occur. Seizures in adults are uncommon.
  • Initial excitation leads to stupor, then coma; severe lethargy alternating with agitation is common, and deep deathlike sleep may occur.
  • Agitation, babbling, confusion, screaming, irritability, hallucinations, dizziness, ataxia, euphoria progressing to muscle jerks, spasms, delirium, racing thoughts, and giddiness may be seen.
  • Headache may last weeks.
  • Illusions are produced by misinterpretation of sensory input.

Causes

• Incorrect mushroom identification by a forager, often an immigrant who mistakes one of the local poisonous varieties for an edible mushroom native to his or her homeland or a novice mushroom harvester
• Intentional ingestion by a suicidal person
• Accidental ingestion by a child who found mushrooms growing around his or her home
• Foul play in which an individual poisoned by someone else
• Inadvertent poisoning from dried mushrooms purchased on the Internet or from other sources where the composition of the mushroom is unreliable or where the mushroom might contaminated with unknown toxic compounds

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Ingestions

Psilocybe species
Tricholoma muscarium
A pantherina
Amanita cothurnata
Amanita smithiana
Amanita strobiliformis
Amanita gemmata

When other members of the Amanita genus are suspected

Ketamine toxicity
Meningoencephalitis
Amphetamine toxicity
Dextromethorphan toxicity
gHydroxybutyrate toxicity

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Several texts, such as Goldfrank's Toxicological Emergencies,¹¹ describe how to determine if the suspect botanical contains amatoxin, a potent toxin found in some of the Amanita species. However, for symptomatic patients, identification of the mushroom by a mycologist is desirable. (See Consultations.)
• Obtain a CBC count because mushroom toxins other than amatoxin (eg, gyromitrin) can cause hemolytic anemia.
• Liver function studies are indicated because possible ingestion of other toxic mushrooms, such as cyclopeptide-type mushrooms, can cause hepatotoxicity.
• Obtain a basic metabolic profile (sodium, potassium, chlorine, carbon dioxide, creatinine, glucose, and calcium levels) to evaluate for fluid and electrolyte disturbances due to other offending ingestants.
• Urine drug screening should be considered, especially if the patient has unexplained behavioral changes, if suicidal intent or foul play is suspected, or if ingestion of other toxins is possible.
• The patient's urine may be analyzed for muscimol to confirm muscimol poisoning, but this test is not typically available in hospital laboratories.
• Chromatographic techniques (eg, thin-layer chromatography [TLC], gas-liquid chromatography [GLC], high-pressure liquid chromatography [HPLC]) are available to detect amanitins, orellanine, muscimol and ibotenic acid, psilocybin, muscarine, and the gyromitrins. However, these techniques are typically unavailable to the general practitioner because they are limited to laboratories conducting research on these compounds.

Imaging Studies

• If the diagnosis is uncertain, and if blunt head trauma is part of the differential diagnosis because of changes in mental status, obtain a plain CT scan of the head before lumbar puncture is performed.

Procedures

• No particular diagnostic procedures are available or needed for most patients with toxicity from mushrooms containing muscimol or ibotenic acid.

TREATMENT

Section 6 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Symptomatic patients may be treated with supportive measures.
• The entire episode usually subsides in 6-8 hours; some symptoms may take up to 2 days to fully resolve.
• Patients with severe agitation or seizures may require benzodiazepines.
• Be aware that respiratory depression has been reported when these agents are administered intravenously (IV).
• Be prepared to support the airway.

Consultations

• Consult a mycologist to assist with mushroom identification. A mycologist can be contacted through the local poison center (in the United States, call 800-222-1222), a mycology club, the North American Mycological Association, a botanical garden, or local university.
• Consultation with a medical toxicologist may be helpful, if available.
• Consult a psychiatrist in cases in which the ingestion may have been a suicidal gesture.

MEDICATION

Section 7 of 11  

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Most patients with poisoning due to ibotenic acid mushrooms can be treated without medications. If patients are severely agitated, anxiolytics may be needed. For seizures lasting longer than 5 minutes, various anticonvulsants have been used. If the patient presents within 1 hour of ingestion, oral administration of activated charcoal may be considered, but adsorption to activated charcoal has not been demonstrated for these constituents.¹² No evidence suggests that routine administration of multiple doses of activated charcoal is useful.

Ipecac syrup should generally be avoided because of the relatively rapid onset of CNS symptoms after ingestion of ibotenic acid mushrooms and the lack of evidence for the effectiveness of ipecac. Although these mushrooms are named A muscaria, few muscarinic effects are noted; therefore, the need for anticholinergic drugs is limited. In addition, because the anticholinergic effects are relatively mild, physostigmine is not indicated.

Drug Category: Anxiolytics and anticonvulsants

Benzodiazepines are first-line agents for controlling seizures in patients with toxicity. They are also helpful in sedating patients with extreme agitation.

Drug Name	Lorazepam (Ativan)
Description	Useful for delirium, seizures, or agitation. By increasing action of GABA (major inhibitory neurotransmitter in brain), may depress all levels of CNS, including limbic and reticular formation.
Adult Dose	4-8 mg PO/IV/IM, administer 4 mg initially, may repeat in 10-15 min
Pediatric Dose	0.05-0.1 mg/kg PO/IV/IM; not to exceed 2 mg/dose
Contraindications	Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma
Interactions	CNS toxicity increases when used concurrently with alcohol, phenothiazines, barbiturates, or MAOIs
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Acute narrow-angle glaucoma, caution with impaired renal or hepatic function; may cause cardiovascular collapse, respiratory depression, blood dyscrasias, hypotension, drowsiness, fatigue, ataxia, or confusion

Drug Name	Midazolam (Versed)
Description	Useful for delirium, seizures, or agitation. Used as alternative to terminate refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to achieve peak EEG effects. Therefore, clinician must wait 2-3 min to fully evaluate sedative effects before starting procedure or repeating dose.
Adult Dose	2.5-5 mg PO/IV/IM, may repeat in 10-15 min
Pediatric Dose	0.05-0.1 mg/kg IV/IM 0.4 mg/kg intranasal; not to exceed 2 mg or adult dose
Contraindications	Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent)
Interactions	Theophylline may antagonize sedative effects; narcotics and erythromycin may accentuate sedative effects because of decreased clearance
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Respiratory depression, acute narrow-angle glaucoma, caution with impaired renal or hepatic function; may cause serious reactions (eg, cardiac arrest, respiratory arrest); common reactions similar to diazepam; may cause euphoria or hallucinations

Drug Name	Phenobarbital (Luminal)
Description	Can be administered PO. In status epilepticus, achieve therapeutic levels as quickly as possible. IV dose may require approximately 15 min to attain peak levels in brain. If injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed those required to control seizures. Use minimal amount required and to wait for anticonvulsant effect to develop before administering second dose.
Adult Dose	Loading dose: 10-20 mg/kg IV or 600-1200 mg; maintenance dose may follow 12 h after loading dose prn
Pediatric Dose	Loading dose: 15-20 mg/kg IV; maintenance dose may follow 12 h after loading dose prn
Contraindications	Documented hypersensitivity; severe respiratory disease, marked impairment of liver function, and nephritis
Interactions	May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients taking anticoagulants may require dose adjustments if drug added to or withdrawn from regimen); coadministration with alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of PO contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur)
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Monitor respirations, especially if used with or shortly after benzodiazepines, observe for hypotension; in prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Administer IV fluids if vomiting becomes prominent, although this is rare.
• Provide psychiatric inpatient care to patients with intentional ingestions and suicidal thinking.

Deterrence/Prevention

• Cautious mushroom hunters eat only one type of mushroom and save a sample in a dry paper bag for later identification, if needed.
• • Identification of mushrooms is best left to experts.
  • Prevention is best achieved by eating only commercially cultivated mushrooms.
• Remove all mushrooms from the site of the ingested mushrooms to avoid accessibility to children.

Prognosis

• The prognosis is excellent because most intoxications are self-limited.

MISCELLANEOUS

Section 9 of 11  

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• Clinical
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• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to refer a suspected suicidal patient to appropriate psychiatric inpatient care
• Failure to provide inpatient care for possible vomiting, seizures, or severe agitation
• Failure to suspect mushroom poisoning
• Misidentification of the offending mushroom; not consulting a mycologist for assistance
• Failure to consider contaminants of dried mushrooms purchased on the Internet or imported from other countries

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Fly agaric (Amanita muscaria).
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
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• Follow-up
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• References

1. Diaz JH. Evolving global epidemiology, syndromic classification, general management, and prevention of unknown mushroom poisonings. Crit Care Med. Feb 2005;33(2):419-26. [Medline].
2. Diaz JH. Syndromic diagnosis and management of confirmed mushroom poisonings. Crit Care Med. Feb 2005;33(2):427-36. [Medline].
3. Watson WA, Litovitz TL, Rodgers GC, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].
4. Michelot D, Melendez-Howell LM. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol Res. Feb 2003;107(Pt 2):131-46. [Medline].
5. Lai MW, Klein-Schwartz W, Rodgers GC, et al. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila). 2006;44(6-7):803-932. [Medline]. [Full Text].
6. Brvar M, Mozina M, Bunc M. Prolonged psychosis after Amanita muscaria ingestion. Wien Klin Wochenschr. May 2006;118(9-10):294-7. [Medline].
7. North American Mycological Association. Annual reports. North American Mycological Association, Toxicology Section. Available at http://www.namyco.org/toxicology. Accessed June 4, 2007.
8. Berger KJ, Guss DA. Mycotoxins revisited: Part I. J Emerg Med. Jan 2005;28(1):53-62. [Medline].
9. Berger KJ, Guss DA. Mycotoxins revisited: Part II. J Emerg Med. Feb 2005;28(2):175-83. [Medline].
10. Fischbein CB, Mueller GM, Leacock PR, et al. Digital imaging: a promising tool for mushroom identification. Acad Emerg Med. Jul 2003;10(7):808-11. [Medline].
11. Goldfrank LR. Mushrooms. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS. Goldfrank's Toxicologic Emergencies. 8^th ed. New York: McGraw-Hill; 2006:1564-76.
12. Chyka PA, Seger D, Krenzelok EP, Vale JA, American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61-87. [Medline]. [Full Text].
13. Poisindex managements, mushrooms – muscimol / ibotenic acid. Poisindex System, internet version [database online]. Greenwood Village (CO): Thomson Micromedex; May 31, 2007.

Article Last Updated: Feb 12, 2008