Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal Anti-inflammatory medicines (NSAIMs), are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects.

The term "nonsteroidal" is used to distinguish these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic.

The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen, all of which are available over the counter in many areas.

Medical uses

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.

NSAIDs are generally indicated for the symptomatic relief of the following conditions:

Rheumatoid arthritis

Osteoarthritis

Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome)

Acute gout

Dysmenorrhoea (menstrual pain)

Metastatic bone pain

Headache and migraine

Postoperative pain

Mild-to-moderate pain due to inflammation and tissue injury

Pyrexia (fever)

Ileus

Renal colic

They are also given to neonate infants whose ductus arteriosus is not closed within 24 hours of birth

Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation. This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A₂.

In 2001 NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.

Adverse effects

The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly prevalent. The two main adverse drug reactions (ADRs) associated with NSAIDs relate to gastrointestinal (GI) effects and renal effects of the agents.

These effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. An estimated 10-20% of NSAID patients experience dyspepsia, and NSAID-associated upper gastrointestinal adverse events are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States, and represent 43% of drug-related emergency visits. Many of these events are avoidable; a review of physician visits and prescriptions estimated that unnecessary prescriptions for NSAIDs were written in 42% of visits.

NSAIDs, like all drugs, may interact with other medications. For example, concurrent use of NSAIDs and quinolones may increase the risk of quinolones' adverse central nervous system effects, including seizure.

Combinational risk

If a COX-2 inhibitor is taken, one should not use a traditional NSAID (prescription or over-the-counter) concomitantly. In addition, people on daily aspirin therapy (e.g. for reducing cardiovascular risk) need to be careful if they also use other NSAIDs, as the latter may block the cardioprotective effects of aspirin.

Cardiovascular

NSAIDs aside from aspirin, both newer COX-2 antagonists and traditional anti-inflammatories, increase the risk of myocardial infarction and stroke. They are not recommended in those who have had a previous heart attack as they increase the risk of death and / or recurrent MI. Naproxen seems least harmful.

NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of symptomatic heart failure in patients without a history of cardiac disease. In patients with such a history, however, use of NSAIDs (aside from low-dose aspirin) was associated with more than 10-fold increase in heart failure. If this link is found to be causal, NSAIDs are estimated to be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs increase mortality risk by approximately 1.2-1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1 for diclofenac.

Erectile dysfunction risk

A 2005 study linked long term (over 3 months) use of NSAIDs, including ibuprofen, with a 1.4 times increased risk of erectile dysfunction. The report by Kaiser Permanente and published in the Journal of Urology, considered that "regular non-steroidal anti-inflammatory drug use is associated with erectile dysfunction beyond what would be expected due to age and other condition". The director of research for Kaiser Permanente added that "There are many proven benefits of non steroidals in preventing heart disease and for other conditions. People shouldn't stop taking them based on this observational study. However, if a man is taking this class of drugs and has ED, it's worth a discussion with his doctor".

Gastrointestinal

The main adverse drug reactions (ADRs) associated with use of NSAIDs relate to direct and indirect irritation of the gastrointestinal (GI) tract. NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins. Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished trophic effects on epithelial mucosa.

Common gastrointestinal ADRs include:

Nausea/Vomiting

Dyspepsia

Gastric ulceration/bleeding.

Diarrhea

Clinical NSAID ulcers are related to the systemic effects of NSAID administration. Such damage occurs irrespective of the route of administration of the NSAID (e.g., oral, rectal, or parenteral) and can occur even in patients with achlorhydria.

Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time, a practice which studies show is not often followed. Recent studies show that over 50% of patients taking NSAIDs have sustained some mucosal damage to their small intestine. Studies show that risk of ulceration is less with nabumetone than with ibuprofen alone.

There are also some differences in the propensity of individual agents to cause gastrointestinal ADRs. Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.

Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations which are claimed to reduce the incidence of gastrointestinal ADRs. Similarly, there is a belief that rectal formulations may reduce gastrointestinal ADRs. However, in consideration of the mechanism of such ADRs and indeed in clinical practice, these formulations have not been shown to have a reduced risk of GI ulceration.

Commonly, gastric (but not necessarily intestinal) adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g. omeprazole, esomeprazole; or the prostaglandin analogue misoprostol. Misoprostol is itself associated with a high incidence of gastrointestinal ADRs (diarrhea). While these techniques may be effective, they prove to be expensive for maintenance therapy.

Inflammatory bowel disease

NSAIDs should be used with caution in individuals with inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration in the gastric lining. Pain relievers such as paracetamol (also known as acetaminophen) or drugs containing codeine (which slows down bowel activity) are safer medications for pain relief in IBD.

Renal

NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions (ADRs). The mechanism of these renal ADRs is due to changes in renal haemodynamics (blood flow), ordinarily mediated by prostaglandins, which are affected by NSAIDs. Prostaglandins normally cause vasodilation of the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of renal function. This is particularly important in renal failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts. Prostaglandins serve to dilate the afferent arteriole; by blocking this prostaglandin-mediated effect, particularly in renal failure, NSAIDs cause unopposed constriction of the afferent arteriole and decreased renal perfusion pressure. Horses are particularly prone to these adverse effects compared with other domestic animal species.

Common ADRs associated with altered renal function include:

Salt and fluid retention

Hypertension (high blood pressure)

These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor (which removes angiotensin II's vasoconstriction of the efferent arteriole) and a diuretic (which drops plasma volume, and thereby RPF) - the so-called "triple whammy" effect.

In rarer instances NSAIDs may also cause more severe renal conditions:

Interstitial nephritis

Nephrotic syndrome

Acute renal failure

Acute tubular necrosis

NSAIDs in combination with excessive use of phenacetin and/or paracetamol (acetaminophen) may lead to analgesic nephropathy.

Photosensitivity

Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs. The 2-arylpropionic acids have proven to be the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac and benzydamine.

Benoxaprofen, since withdrawn due to its hepatotoxicity, was the most photoactive NSAID observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism. While ibuprofen has weak absorption, it has been reported to be a weak photosensitising agent.

During pregnancy

NSAIDs are not recommended during pregnancy, particularly during the third trimester. While NSAIDs as a class are not direct teratogens, they may cause premature closure of the fetal ductus arteriosus and renal ADRs in the fetus. Additionally, they are linked with premature birth and miscarriage. Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies.. Additionally, Indomethacin is used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal renal blood flow.

In contrast, paracetamol (acetaminophen) is regarded as being safe and well-tolerated during pregnancy. Doses should be taken as prescribed, due to risk of hepatotoxicity with overdoses.

In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.

Other

Common adverse drug reactions (ADR), other than listed above, include: raised liver enzymes, headache, dizziness. Uncommon ADRs include: hyperkalaemia, confusion, bronchospasm, rash. Rapid and severe swelling of the face and/or body. Ibuprofen may also rarely cause irritable bowel syndrome symptoms. NSAIDs are also implicated in some cases of Stevens–Johnson syndrome.

Most NSAIDs penetrate poorly into the central nervous system (CNS). However, the COX enzymes are expressed constitutively in some areas of the CNS, meaning that even limited penetration may cause adverse effects such as somnolence and dizziness.

In very rare cases, ibuprofen can cause aseptic meningitis.

As with other drugs, allergies to NSAIDs might exist. While many allergies are specific to one NSAID, up to 1 in 5 people may have unpredictable cross-reactive allergic responses to other NSAIDs as well.

Drug Interactions

NSAIDs reduce renal blood flow and thereby decrease the efficacy of diuretics, and inhibit the elimination of lithium and methotrexate.

NSAIDs cause hypocoagulability, which may be serious when combined with other drugs that also decrease blood clotting, such as warfarin.

NSAIDs may aggravate hypertension (high blood pressure) and thereby antagonize the effect of antihypertensives, such as ACE Inhibitors.

NSAIDs may interfere and reduce efficiency of SSRI antidepressants

Mechanism of action

Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A₂). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927–2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin). Many aspects of the mechanism of action of NSAIDs remain unexplained, for this reason further COX pathways are hypothesized. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed. NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin synthase.

Antipyretic activity

NSAIDS have antipyretic activity and can be used to treat fever. Fever is caused by elevated levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. PGE2 signals to the hypothalamus to increase the body's thermal set point. Ibuprofen has been shown to be more effective as an antipyretic than acetaminophen. Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.

Classification

NSAIDs can be classified based on their chemical structure or mechanism of action. Older NSAIDs were known long before their mechanism of action was elucidated and were for this reason classified by chemical structure or origin. Newer substances are more often classified by mechanism of action.

Naproxen

Fenoprofen

Ketoprofen

Dexketoprofen

Flurbiprofen

Oxaprozin

Loxoprofen

Acetic acid derivatives

Indomethacin

Sulindac

Etodolac

Ketorolac

Diclofenac (Safety alert by FDA)

Nabumetone

Enolic acid (Oxicam) derivatives

Piroxicam

Meloxicam

Tenoxicam

Droxicam

Lornoxicam

Isoxicam

Fenamic acid derivatives (Fenamates )

Mefenamic acid

Meclofenamic acid

Flufenamic acid

Tolfenamic acid

Selective COX-2 inhibitors (Coxibs)

Celecoxib (FDA alert) Rofecoxib (withdrawn from market) Valdecoxib (withdrawn from market)

Parecoxib FDA withdrawn, licenced in the EU

Lumiracoxib TGA cancelled registration

Etoricoxib FDA withdrawn, licenced in the EU

Firocoxib used in dogs and horses

Sulphonanilides

Nimesulide (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)

Others

Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX inhibitor

Lysine clonixinate

Main practical differences

NSAIDs within a group will tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds tend to be with regards to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile.

Regarding adverse effects, selective COX-2 inhibitors have lower risk of gastrointestinal bleeding, but a substantially more increased risk of myocardial infarction than the increased risk from nonselective inhibitors. Some data also supports that the partially selective nabumetone is less likely to cause gastrointestinal events. The nonselective naproxen appears to be risk-neutral with regard to cardiovascular events.

A consumer report noted ibuprofen, naproxen and salsalate to be less expensive than other NSAIDs and to be essentially as effective and safe as any of them when used appropriately in treating osteoarthritis and pain.

Pharmacokinetics

Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are absorbed well from the stomach and intestinal mucosa. They are highly protein-bound in plasma (typically >95%), usually to albumin, so that their volume of distribution typically approximates to plasma volume. Most NSAIDs are metabolised in the liver by oxidation and conjugation to inactive metabolites which are typically excreted in the urine, although some drugs are partially excreted in bile. Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.

Ibuprofen and diclofenac have short half-lives (2–3 hours). Some NSAIDs (typically oxicams) have very long half-lives (e.g. 20–60 hours).

Chirality

Most NSAIDs are chiral molecules (diclofenac is a notable exception). However, the majority are prepared in a racemic mixture. Typically, only a single enantiomer is pharmacologically active. For some drugs (typically profens), an isomerase enzyme exists ''in vivo'' which converts the inactive enantiomer into the active form, although its activity varies widely in individuals. This phenomenon is likely to be responsible for the poor correlation between NSAID efficacy and plasma concentration observed in older studies, when specific analysis of the active enantiomer was not performed.

Ibuprofen and ketoprofen are now available in single, active enantiomer preparations (dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-effect profile. Naproxen has always been marketed as the single active enantiomer.

Selective COX inhibitors

COX-2 inhibitors

The discovery of COX-2 in 1991 by Daniel L. Simmons at Brigham Young University raised the hope of developing an effective NSAID without the gastric problems characteristic of these agents. It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastroprotective prostaglandins.

COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, these protective effects are lost and ulcers of the stomach or duodenum and potentially internal bleeding can result. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.

The relatively selective COX-2 inhibiting oxicam, meloxicam, was the first step towards developing a true COX-2 selective inhibitor. Coxibs, the newest class of NSAIDs, can be considered as true COX-2 selective inhibitors, and include celecoxib, rofecoxib, valdecoxib, parecoxib and etoricoxib.

Acetaminophen does also work mainly by blocking COX-2, unlike the newly developed COX-2 inhibitors it has weaker peripheral inhibitory activity.

Controversies with COX-2 inhibitors

While it was hoped that this COX-2 selectivity would reduce gastrointestinal adverse drug reactions (ADRs), there is little conclusive evidence that this is true. The original study touted by Searle (now part of Pfizer), showing a reduced rate of ADRs for celecoxib, was later revealed to be based on preliminary data - the final data showed no significant difference in ADRs when compared with diclofenac.

Rofecoxib however, which has since been withdrawn, had been shown to produce significantly fewer gastrointestinal ADRs compared with naproxen. This study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs - a statistically insignificant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a statistically significant relative risk of cardiovascular events of 1.97 versus placebo - a result which resulted in the worldwide withdrawal of rofecoxib in October 2004.

COX-3 inhibitors

Simmons also co-discovered COX-3 in 2002 and analyzed this new isozyme's relation to paracetamol (acetaminophen), arguably the most widely used analgesic drug in the world. The authors postulated that inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.

The relevance of this research has been called into question as the putative COX-3 gene encodes proteins with completely different amino acid sequences than COX-1 or COX-2. The expressed proteins do not show COX activity and it is unlikely that they play a role in prostaglandin mediated physiological responses.

Veterinary use

Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves. The best effect is obtained by combining a short-term local anesthetic such as lidocaine with an NSAID acting as a longer term analgesic. However, as different species have varying reactions to different medications in the NSAID family, little of the existing research data can be extrapolated to animal species other than the specific species studied, and the relevant government agency in one area will sometimes prohibit uses which are approved in other jurisdictions.

For example, ketoprofen's effects have been studied in horses more than in ruminants but, due to controversy over its use in racehorses, veterinarians treating livestock in the United States more commonly prescribe flunixin meglumine, which while labeled for use in such animals is not indicated for post-operative pain.

In the United States, meloxicam is approved for use only in canines, whereas (due to concerns about liver damage) it carries warnings against its use in cats except for one-time use during surgery. In spite of these warnings, meloxicam is frequently prescribed "off-label" for non-canine animals including cats and livestock species. In other countries (for example EU and CAN), by contrast, there is a label claim for use in cats.

References

ar:مضادات التهاب لاستيرويدية bg:НСПВС bs:Nesteroidni antiupalni lijekovi ca:Antiinflamatori no esteroïdal cs:Nesteroidní antiflogistikum cy:Cyffur gwrthlid ansteroidol da:NSAID de:Nichtsteroidales Antirheumatikum es:Antiinflamatorio no esteroideo eu:Antiinflamatorio ez esteroideo fa:داروهای ضد التهاب غیر استروئیدی fr:Anti-inflammatoire non stéroïdien ga:Druga Frith-athlastach Neamhstéaróideach ko:비스테로이드 항염증제 hr:Nesteroidni protuupalni lijekovi it:FANS hu:Nem-szteroid gyulladáscsökkentő gyógyszerek nl:NSAID ja:非ステロイド性抗炎症薬 no:Ikkesteroid antiinflammatorisk middel pa:ਨੌਨ ਸਟੀਰੌਇਡਲ ਐਂਟੀ ਇਨਫ਼ਲਾਮੇਟਰੀ ਦਵਾਈਆਂ pl:Niesteroidowe leki przeciwzapalne pt:Anti-inflamatórios não esteroides ru:Нестероидные противовоспалительные препараты simple:Non-steroidal anti-inflammatory drug sk:Nesteroidné antiflogistikum sr:Нестероидни антиинфламаторни лек sh:Nesteroidni antiupalni lijekovi fi:Tulehduskipulääke sv:NSAID ta:அழற்சிக்கு எதிரான இயக்க ஊக்கிகள் இல்லாத மருந்துகள் th:ยาแก้อักเสบชนิดไม่ใช่สเตอรอยด์ tr:Non steroidal antienflamatuar ilaçlar ur:لااسٹیرودی مانع سوزش دوا vi:Thuốc chống viêm không steroid zh:非甾体抗炎药

name	Jessica Rogers
residence	Springfield, Virginia, USA
birth date	March 09, 1997
birth place	Sao Carlos, Brazil
height	(2010)
weight	(2011)
sport	Wheelchair racing Swimming Wheelchair Basketball
event	All Events - Track 100 Brestroke - Swimming 200 Brestroke - Swimming
team	FISH swim team, McLean, VA
coach	Andy Ciprano
show-medals	}}

Jessica Rogers is an accomplished athlete participating in Wheelchair basketball, wheelchair racing and numerous swimming events. She is also the founder of the ''Caudal Regression Syndrome Association'', an organization for information sharing, support, and networking.

Biography

Rogers has lumbo sacral agenesis/caudal regression syndrome and bilateral leg amputations. Her spine ends at approximately T 7-10. She has resulting paralysis and very small lower anatomy. She has one kidney.

Early life

Rogers spent the first part of her life in an isolated crib in a care facility for adults with severe cognitive limitations. She was adopted from Brazil into a single parent household by Phyllis Rogers, as one of eight children, all of whom have disabilities. Three of her brothers and sisters are hearing-impaired, whilst Jessica uses a wheelchair. Rogers overcame her initial delays and proved to be a determined and bright young lady.

In the news

In July 2005, Rogers made national headlines while attending the National Junior Disability Championships (NJDC) in Tampa, Florida. She was there to participate in the 25-meter breast stroke event. Rogers and her family took a side trip to Busch Gardens. While at the park Rogers was denied access to three Busch Gardens rides, including the 6-inch-deep kiddy water rapids. Ride attendants at Busch Gardens called their managers and turned her away, not wanting to be responsible if she were hurt.

When Rogers returned to the NJDC games the next day, her wheelchair carried a sign asking fellow athletes to boycott Busch Gardens because of this incident. After going to the news media about the Busch Gardens incident, Busch Gardens later on allowed Jessica on some of the park's rides.

Filmography

Documentaries and other television appearances include:

First aired	Title	Episode	Distributor	Produced by	Awards
			valign="top" style="font-size:90%"

Charity work

Jessica Rogers is the founding member of The Caudal Regression Syndrome (CRS) Association, the only known active association offering information, support, and networking for persons with CRS and their families- anywhere in the world. Jessica started the association as a way to bring together these resources after years of finding it hard to find others who have CSR and even information on her condition of lumbo sacral agenesis/caudal regression syndrome.

Sports career

Early sports involvement

Jessica Rogers started participating in her first organized sport activity at the age five years. Since that time Jessica has taken part in numerous sporting events which have included wheelchair racing, field, Ice sledge hockey, swimming, wheelchair basketball, and hand cycling. In spite of the fact Jessica has to coordinate both the schedule and the expense of her many activities with the demands of 7 other siblings in her family, she has demonstrated her abilities in many areas. On the basketball court Jessica is fearless and fast and can read the court well.

Her hook shot under pressure has resulted in team wins on numerous occasions. She always has an encouraging word for other players and has worked with younger players to help them develop their skills. A frequent participant in the National Junior Disability Championships with her team, the ''Bennett Blazers'', she had to stop competing when she outgrew her racing wheelchair.

2010 the ''IM Able Foundation'' a organization whose goal is to help disabled individuals find the physical fitness modality that meets their needs, put Rogers back on track, literally, with a new racing wheechair. The same year she returned to wheelchair racing Rogers went on to gold in the 100, 200, 400 and 800-meter events at the 2010 NJDC.

Swimming

In 2009 aged 12 Rogers joined FISH, a local Potomac Valley Swimming team and USA Swimming Club member. Rogers was an unknown to the Potomac Valley Swim leagues, but had already made her mark on the junior national scene as a record holder in 7 swimming events. The reason Jessica says she joined FISH looking was she was looking for some training closer to home to help her bridge the gap between junior championships and Paralympics level swimming.Jessica trains at the new FISH location, Audrey Moore RECenter at Wakefield Park, under the direction of Coach Julie and Coach Megan.

Paralympic athletes are classed according to the impact their level of disability has on their swimming. Jessica swims in an S-4 classification, meaning that she is using only her arms for swimming. In 2009, Jessica Rogers competed in the Eastern Regional Junior Disability Meet in New Jersey. She swam in 8 events, placing first in all, and easily qualifying for junior nationals. Most importantly, Jessica's times have dropped significantly, so that she now meets the official cut off times in all of these events for the Paralympic Trials.

Rogers's current goal is to make the 2012 USA Paralympics team, swimming in 50M and 100M events at the 2012 Summer Paralympics, in London, England.

Major Achievements

In 2011 Jessica Rogers was selected by ''SPORTS 'N SPOKES'' Magazine as their Junior Athlete of the Year. As Prt of her winnings for being selected Junior Althete of the Year, Jessica received a beautifully engraved plaque, a year's subscription to ''SPORTS 'N SPOKES'', and a brand new custom fitted wheelchair courtesy of TiLite Wheelchairs.

Awards and Achievements include:

2011: Parapan American Games, Guadalajara, Mexico, silver medal 100 M breastroke

2011: ''SPORTS 'N SPOKES'' Magazine's Junior Athlete of the Year

2010: Junior National Champion, 100, 200, 400, 800 M wheelchair track

2010: ''Im Able Foundation's'' Racing Wheelchair Recipient

2010: American Paralympic record holder, women's 100 SCY breaststroke

2010: American Paralympic record holder, women's 200 SCY IM

2010: Canadian American Paralympic National Champion women's 100 M breastroke

2009: Canadian American Paralympic National Champion women's 100 M breastroke

2009: Canadian American Paralympic National Champion women's 200 M breastroke

2008: National Junior Disability Championships, First place 100Meter, 200Meter, 400Meter wheelchair track

See also

Caudal regression syndrome

References

External links

Caudal Regression Syndrome Association- Organization founded by Jessica Rogers

A Child's Courage - The REBUILT: The Human Body Shop segment featuring Jessica Rogers

‪

Category:Living people Category:1997 births Category:American swimmers Category:American amputees Category:American disabled sportspeople Category:Disabled sportspeople Category:American wheelchair basketball players

name	Mandy Moore
alt	Moore smiling faintly at a 2009 concert promoted by Gain Detergent. She wears a dark blazer and a black and white striped blouse, and the word "Gain" is visible in the background.
background	solo_singer
birth name	Amanda Leigh Moore
birth date	April 10, 1984
birth place	Nashua, New Hampshire, U.S.
origin	Orlando, Florida, U.S.
spouse	Ryan Adams (2009-present)
genre	Pop, dance, folk pop, pop rock
occupation	Singer-songwriter, actress, model, fashion designer
years active	1999–present
label	Epic, Sire, The Firm Music, EMI, Storefront Recordings, RED Distribution
website	}}

Amanda Leigh "Mandy" Moore (born April 10, 1984) is an American singer-songwriter, actress and fashion designer. Moore became famous as a teenager in the late 1990s, after the release of her teen pop albums ''So Real,'' ''I Wanna Be with You,'' and ''Mandy Moore.'' In 2007, she took an adult pop-folk direction with the release of ''Wild Hope''. Her most recent album, ''Amanda Leigh,'' was released on May 26, 2009. Moore has sold more than 10 million records worldwide. Moore subsequently branched out into film, starring in 2002's ''A Walk to Remember'' and later in other movies, such as ''Chasing Liberty'', ''Saved!'' and ''License to Wed''. Most recently Moore provided the voice of Rapunzel in ''Tangled''. In April 2011, she ranked 5th in ''People''s annual Most Beautiful issue.

Early life

Moore was born in Nashua, New Hampshire. Her mother, Stacy (née Friedman), is a former news reporter who once worked for the ''Orlando Sentinel'', and her father, Donald "Don" Moore, is a pilot for American Airlines. Moore's father is of Irish and Cherokee descent, and her mother is of half English and half Jewish ancestry. Moore, who has an older brother Scott and a younger brother Kyle, grew up in Longwood, Florida, outside of Orlando, where the family moved shortly after her birth because of her father's job as an airline pilot. She was raised Catholic (though she is no longer practicing), and attended Bishop Moore High School, in Orlando, as well as Lake Brantley High School in Altamonte Springs.

Moore's interest in singing grew after seeing the musical ''Oklahoma!''. She was also encouraged to perform by her English-born maternal grandmother, who was her inspiration. Some of Moore's first public exposure occurred when she sang the national anthem at several Florida sporting events. She subsequently came to the attention of the head of the artists and repertoire department at Epic Records after his friend, a FedEx employee, overheard her as she sang at a recording studio.

Music career

1999–2002

''So Real''

Moore toured with N'SYNC throughout the first half of 1999. Her debut album, ''So Real,'' was released in December 1999 and reached No.31 on the U.S. ''Billboard'' 200 album charts. Unfortunately for her image, at the time of the album's release, reviewers considered Moore the latest in a series of heavily-marketed female teen singers described as "pop princesses," akin to Britney Spears and Christina Aguilera. ''Entertainment Weekly'' Magazine's review of ''So Real,'' written by Elizabeth Vincentelli, accused Moore's songs of revolving around "not-yet-experienced love," of having been performed with "suffocating professionalism," and called the album's ballads "nauseating."

Moore reached mainstream radio later, and at a younger age, than Aguilera and Spears had, and she was initially not as successful as they were. However, ''So Real'' was still certified platinum in the U.S. in early 2000 and sold nearly one million copies. Moore's debut teen-oriented pop hit single "Candy," which Yahoo! Movies described as "strangely provocative," peaked just outside the top 40 on the U.S. ''Billboard'' Hot 100 charts, and was certified gold. The single was more successful in Europe, especially in the UK, where it reached number 6. Allmusic called the single "mediocre" and "typical," containing lyrics that described love "in terms of sugar treats."

''I Wanna Be with You''

Moore released ''I Wanna Be with You'' in May 2000. The album, which was mostly completed with synthesizers, bass, guitar, and drums comprised new songs alongside tracks and remixes from ''So Real.'' Several reviewers criticized it on the basis that it was a remix album and not a true follow-up, with Allmusic accusing its style of being "trashier, flashier, gaudier, and altogether more disposable" than that of ''So Real.'' It peaked at No.21 on the ''Billboard'' 200, was certified gold in the U.S., selling nearly 1,000,000 copies. The title track, "I Wanna Be with You," was the album's only single and reached No.24 on the Hot 100, Moore's highest peak to date. It was also featured on the soundtrack of the film ''Center Stage'' in 2000.

''Mandy Moore''

In June 2001, Moore released her second full-length album, her third overall, the self-titled album ''Mandy Moore.'' She promoted the album with her first headlining concert, "Mandy Moore Live@ShoutBack." The album contained uptempo tracks and influences from Eastern music, and Allmusic described it as a "lush, layered production." It received mixed reviews from other critics. The album debuted at No.35 on the ''Billboard'' 200, and was later certified gold in the U.S., selling 443,000 copies. The lead single was "In My Pocket," which ''Entertainment Weekly'' said contained "pumping, Indian influenced Euro disco." The album's follow-up single was titled "Crush." The early 2002 release of the final single, "Cry", tied in with the film ''A Walk to Remember,'' Moore's debut as a lead actress.

In 2006, Moore commented on her early albums, noting that although she believed that her first album was appropriate for her age at the time when she released it, she felt it "sucked" and that her first albums were "just awful." Moore also said that she "would give a refund to everyone who bought my first two albums" if she could; during a radio interview in April 2006, the show's co-host—who had seen her comments—asked her for a refund on the first album, a request that Moore fulfilled.

2003–2006

In October 2003, Moore released her fourth album ''Coverage'', which Allmusic characterized as a "leap to musical maturity" and which ''Entertainment Weekly'' called an "effort to shed her bubblegum-blond image". The album peaked at No.14 on the ''Billboard'' 200; but "Have a Little Faith in Me" and "Senses Working Overtime", its only two singles, did not perform well on the charts. Moore's cover of "I Feel the Earth Move" appeared on ''Love Rocks'', a compilation CD of songs from gay rights supporters.

Due to creative differences between Moore and her label, a split was announced. The company released the hits compilation album ''The Best of Mandy Moore'', which reached No.148 on the ''Billboard'' 200 in November 2004 as a final obligation to Moore's contract. Another compilation, ''Candy'', followed in 2005. During this time period, the only music Moore had recorded was a song demo, "Hey!", written by James Renald, and a cover version of Lori McKenna's "Beautiful Man". Moore also voiced the character "Nita" in the 2006 film, ''Brother Bear 2''.

2007–2009

In early 2006, Moore stated that she missed her music career and that singing is what she was the "most passionate about." Moore had signed to Sire Records after her contract with Epic Records ended, but she left the company in May 2006. She signed with a new EMI Music-owned record company, The Firm, in July that year, describing her new contract as "especially exciting," and adding that she left Sire Records because she did not want to "follow the mainstream," but rather have "complete control and freedom" over her work. Moore's new album, ''Wild Hope,'' was released on June 19, 2007, and includes collaborations with artists Chantal Kreviazuk, Rachael Yamagata, Lori McKenna and The Weepies. Moore stayed alone in a house in Woodstock in Upstate New York while recording the album in late 2006. She performed new material from ''Wild Hope'' at the Sundance Film Festival; her first single, "Extraordinary," premiered on her MySpace profile on January 29, 2007. Moore performed the song at the Brick Awards on April 12, 2007 and launched a tour in the summer of 2007.

The album was released in the USA in June 2007 to positive reviews. It fared moderately well on the charts, debuting at number thirty on the ''Billboard'' 200 (Moore's third highest charting album in the U.S.), and at number 84 in Canada. In August 2007, Moore toured with Paula Cole, and Rachael Yamagata, playing at mid-size venues in the United States and Canada. ''Wild Hope'' was placed at number 10 on ''Entertainment Weekly's'' "The Must List" and also named Reader's Choice for that August 10 issue, two months after its release. Moore surprised many with a free concert in Boston on July 18, 2007.

On February 23, 2008, Moore released ''Wild Hope'' in Australia, and subsequently toured with Ben Lee and the West Australian Symphony Orchestra in Western Australia, supporting Kelly Clarkson on her tour. In October 2008, Moore posted on her website blog live videos of three new songs she's been working on, along with singer-songwriter, pianist and guitarist Mike Viola. It was at first expected to a be a duo album between the two, but then in January 2009, it was revealed it would be a solo album with a collaboration with him, slated for release in April 2009.

On June 2009, Moore performed 5 tracks of her new ''Amanda Leigh'' album, including “Nothing Everything” and “Love To Love Me Back,” at the Walmart Soundcheck show.

In May 2009, she released her latest album, ''Amanda Leigh,'' to generally positive reviews. ''Rolling Stone'' said about the album: "the title is taken from the singer's real first and middle names, the acoustic instrumentation emits a cozy campfire glow, and the album was recorded in a modest basement home studio. Message: This is real music, not computerized starlet pop." ''Time'' Magazine said that the album was "impeccably recorded." An article on the album by ''Paper'' Magazine said, "Mandy (in the album)... shows real thoughtful and emotional depth." ''Paper'' concluded that "Moore is a far better musician than she's often given credit for."

Moore has a total of singles sales in Australia of more than 241,000 copies, and was ranked at # 281 on the 1000 artists chart of ARIA Music Decade Charts (1980–2010).

2010–present

In 2010, Moore voiced Rapunzel in Disney animation film ''Tangled'' and recorded several songs for the soundtrack, including ''I See the Light'', which she performed live during the Oscar presentation in February 2011.

Acting career

2000–2002

During the summer of 2000, Moore hosted a half-hour MTV talk show, ''The Mandy Moore Show'', which was renamed ''Mandy'' a year later. Moore was also a Neutrogena spokesperson, appearing in commercials and print ads for the product. She has modelled for Penshoppe in the Philippines, Coach handbags in Japan, and was a spokesperson for the School and Youth Programs of the Leukemia & Lymphoma Society. Her first acting role was in the straight-to-video children's film ''Magic Al and the Mind Factory'' in which she plays the character of Brittany Foster.

In 2001, Moore appeared in a small part as the mean and popular cheerleader Lana Thomas opposite actresses Anne Hathaway and Julie Andrews in the film ''The Princess Diaries''. During the film, Moore's character performs "Stupid Cupid," a song from the film's soundtrack. She also had a voiceover role in ''Dr. Dolittle 2'' as the Girl Bear Cub. In 2002, Moore had her first starring role in a major feature film in ''A Walk to Remember'', which co-starred Shane West. Based on the novel by Nicholas Sparks, the film revolved around the developing romance between a Protestant minister's daughter Jamie Sullivan (Moore) and an unruly teenager Landon Carter (West). The film was moderately successful, bringing in $41 million in the United States, and establishing Moore's status as a lead actress. Although the film received mainly negative reviews, Moore received several positive notices for her performance, with critic Roger Ebert calling her "quietly convincing". At that summer's MTV Movie Awards, Moore won an award for "Breakthrough Female Performance" for the role. The same year, she voiced the ''Final Fantasy VII'' character Aerith Gainsborough in the Square-Disney crossover video game ''Kingdom Hearts'', was featured in the music video for Elton John's "Original Sin", and was ranked number sixty-seven in ''Stuff'' magazine's "102 Sexiest Women in the World".

2003–2005

In 2003, Moore starred in the romantic comedy film ''How to Deal'', which failed to draw in teenage crowds in the U.S. and grossed a total of $14 million domestically. Her next film was 2004's ''Chasing Liberty,'' a romantic comedy that grossed approximately $12 million. Both films received negative reviews; however, Ebert once again singled Moore's performances out, noting in his review of ''How to Deal'' that Moore has "an unaffected natural charm" and "almost makes the movie worth seeing," and adding in his ''Chasing Liberty'' review that she has "undeniable screen presence and inspires instant affection." Other critics described her as an "actress of limited range," though one review of ''Chasing Liberty'' noted that she was the "most painless of former pop princesses." Later in 2004, Moore appeared in a lead role in the religion satire ''Saved!'' in which she played Hilary Faye, a proper and popular girl at a Christian school. The film was positively reviewed, though it did not receive a wide release. Moore received praise for her performance, with one critic calling her a "demented delight" and another naming it her best performance to date. She sang a cover version of The Beach Boys 1966 hit "God Only Knows", with Michael Stipe, that bookended the movie.

In 2005, Moore lent her voice to the film ''Racing Stripes'' as Sandy the white horse and appeared on the television series ''Entourage;'' she was also originally scheduled to star in the films ''Cursed,'' ''Havoc,'' and ''The Upside of Anger,'' all of which were eventually released in 2005 without Moore's involvement.

2006–2007

In 2006, Moore guest-starred in two episodes of ''Scrubs'': "My Half-Acre" and "Her Story II". The same year, she lent her voice to ''The Simpsons'', playing Tabitha Vixx in the episode "Marge and Homer Turn a Couple Play".

Moore also appeared in the film ''American Dreamz'', which was released in April 2006. In the film, she played a deranged contestant on a television series modeled after ''American Idol''. Director Paul Weitz stated that he had Moore in mind for the role before she was cast, explaining that "there's something inherently sweet about Mandy; it makes it all the more interesting to see her in a villainess role". Moore has said that she enjoys playing mean-spirited characters but fears being typecast as a villain. ''American Dreamz'' opened at number nine at the U.S. box office, eventually totaling barely $7 million, and received mixed reviews; critic Owen Gleiberman of ''Entertainment Weekly'', however, wrote that Moore and co-star Hugh Grant have a "wicked barbed chemistry" in their roles, while ''Variety''s Robert Koehler said Moore's role was a "pitch-perfect study of a woman for whom a reality show is reality".

Later that year, in what ComingSoon.net's review described as a "surprisingly good performance", Moore voiced Nita, the heroine of the Disney animated sequel ''Brother Bear 2'', which was released directly-to-DVD on August 29. She was also originally cast to appear in that year's ensemble film ''Bobby'', but was replaced by Mary Elizabeth Winstead.

Moore, citing her conservative upbringing, has expressed dissatisfaction with her appearance on a May 2006 cover of ''Cosmopolitan''; the magazine's headline is "orgasms unlimited", which refers to an article unrelated to her. In her movie following this, ''Because I Said So'', co-starring Gabriel Macht, Lauren Graham and Diane Keaton, Moore's character describes in detail the feeling of an orgasm to her mother. It was released on February 2, 2007 and received mixed reviews. In ''License to Wed'', Moore portrays a young bride-to-be who has to complete a three-week prenup course before her wedding. Co-starring John Krasinski as her fiance and Robin Williams as a priest, the film was released on July 3, 2007 to mostly negative reviews. Nevertheless, ''Variety'' described Moore's performance as "appealing." In 2007, Moore returned to the small screen in an episode of ''How I Met Your Mother'' entitled "Wait for It".

2009–present

After a break of almost two years from big screen roles, Moore filmed the romantic comedy ''Swinging with the Finkels'' in the United Kingdom in 2009 for a 2011 release. Moore also starred with actor Kellan Lutz in the 2010 film, ''Love, Wedding, Marriage''. She was a guest star on the sixth season finale of ''Grey's Anatomy'' on May 20, 2010, her first television role since 2007. She returned in a guest role for an episode of the show's seventh season. Also that year, Moore voiced Princess Rapunzel in the CGI animated film ''Tangled''. Moore, alongside Zachary Levi, performed the film's theme song, "I See the Light" at the 83rd Academy Awards where it was nominated for Best Original Song.

In October 2011, it was announced that she is set to star in an ABC comedy titled ''Us and Them''.

Along with her voice role in the upcoming 2012 ''Tron: Uprising'' animated series, she is also set to be the title character voice in the Disney Junior series ''Oki’s Oasis''.

Fashion career

Moore branched into the fashion world in 2005 with her own fashion line named ''Mblem.'', a brand of contemporary knitwear and cashmere. One of her aims was to provide clothing for taller women (Moore herself is 5'10). In February 2009, Moore announced that the line would be shutting down, but that she hoped to reenter the fashion world again under different circumstances in the future.

Philanthropy

According to a press release from her own official website, Moore was involved in teaming up with nonprofit organization PSI, and its subsidiary, Five and Alive, in fighting malaria in Africa.

According to ''USA Today'', Moore was also involved in serving as the Honorary Chairperson of the Leukemia and Lymphoma Society's division on awareness for youth. She served as a spokesperson by helping young people be aware of the seriousness of leukemia and lymphoma. She also serves as the spokesperson for Cervical Cancer Awareness Month, held every January. In addition, to increase cervical cancer awareness, Moore teamed up with Dr. Yvonne Collins, The Gynecologic Cancer Foundation (GCF), and GlaxoSmithKline (GSK).

Personal life

Her relationships with Adam Goldstein aka DJ AM, singer Billy Crawford, tennis player Andy Roddick, and actors Wilmer Valderrama and Zach Braff, as well as her marriage to singer Ryan Adams, have become the subject of media coverage. Moore and Adams were married on March 10, 2009, in Savannah.

Moore has become a fan of mixed martial arts, often attending UFC events.

As to her religious beliefs, Moore considers herself spiritual, and has said that she does not think of herself as Christian.

Reporters have mentioned that Moore has a slight lisp in her performances, but Moore denied having one when asked by a fan on her official blog.

Social networking

Moore is the ambassador for the UN Foundations’s “Nothing But Net’s” campaign. The campaign launched a mass distribution of mosquito nets, ensuring that young children, women and newborn babies are not infected with malaria. Through her use of social networking she has brought awareness to the cause. In August 2011, the campaign used the Town hall function on Facebook for the first time ever. Almost $5,000 was raised immediately. With nearly two million twitter followers, Moore continues to tweet about fundraising for the foundation. For further awareness of the cause she created a page on the commonly used site, crowdrise.com.

Discography

Studio albums

''So Real'' (1999)

''I Wanna Be with You'' (2000)

''Mandy Moore'' (2001)

''Coverage'' (2003)

''Wild Hope'' (2007)

''Amanda Leigh'' (2009)

Compilations

''The Best of Mandy Moore'' (2004)

''Candy'' (2005)

''Super Hits'' (2008)

DVDs

''Mandy Moore – The Real Story'' (2001)

''Coverage Bonus DVD'' (2003)

''The Best of Mandy Moore'' (2004)

Filmography

+ Film
! Year	! Title	! Role	! Notes
2000	''Magic Al and the Mind Factory''	Brittany Foster
2001		Lana Thomas
2001	''Dr. Dolittle 2''	Girl Bear Cub	Voice
2002	''A Walk to Remember''	Jamie Sullivan	MTV Movie Award for Best Breakthrough Performance – FemaleTeen Choice Award for Choice Breakout Performance – FemaleTeen Choice Award for Choice Movie Chemistry Nominated—Teen Choice Award for Choice Movie Actress – Drama/Action Adventure
2002		Lisa
2003	''How to Deal''	Halley Martin
2004	''Chasing Liberty''	Anna Foster
2004	''Saved!''	Hilary Faye	Nominated—Teen Choice Awards
2005	''[[Racing Stripes''	Sandy	Voice
2006	''American Dreamz''	Sally Kendoo
2006	''Brother Bear 2''	Nita	Voice
2006	''Romance & Cigarettes''	Baby Murder
2007		Milly Wilder
2007	''License to Wed''	Sadie Jones
2007		Lucy Riley
2007	''Southland Tales''	Madeline Frost Santaros
2010	''Swinging with the Finkels''	Sarah Finkel
2010	''Tangled''	Rapunzel	Voice
2011	''Love, Wedding, Marriage''	Ava

+ Television
! Year	! Title	! Role	! Notes
2003	''Clone High''	Herself?	1 episode
2003	''Punk'd''	Herself	1 episode
2005	''Criss Angel: Mindfreak''	Herself	1 episode
2005		Herself/ Aquagirl	"Oh, Mandy" (Season 2, Episode 8)"I Love You Too" (Season 2, Episode 9)"The Bat Mitzvah" (Season 2, Episode 10)"Blue Balls Lagoon" (Season 2, Episode 11)"Exodus" (Season 2, Episode 13)
2006		Julie Quinn	"My Half-Acre" (Season 5, Episode 9)"Her Story II" (Season 5, Episode 10)
2006		Tabitha Vixx (voice)	"Marge and Homer Turn a Couple Play" (Season 17, Episode 22)
2007	''How I Met Your Mother''	Amy
2010	''Grey's Anatomy''	Mary Portman	"Sanctuary" (Season 6, Episode 23)"Death and All His Friends" (Season 6, Episode 24)"That's Me Trying" (Season 7, Episode 7)"These Arms of Mine" (Season 7, Episode 6)
2012	''Tron: Uprising''	Mara	Voice (In production)

+ Video game
! Year	! Title	! Role	! Notes
2002	''Kingdom Hearts''	Aerith Gainsborough	Voice (English version)

References

External links

Category:1984 births Category:Living people Category:Actors from Florida Category:Actors from New Hampshire Category:American child actors Category:American child singers Category:American female singers Category:American film actors Category:American folk singers Category:American musicians of Irish descent Category:American people of English descent Category:American people of Cherokee descent Category:American people of English descent Category:American people of Irish descent Category:American people of Jewish descent Category:American pop singers Category:American people of Native American descent Category:American singer-songwriters Category:American television actors Category:American voice actors Category:Child pop musicians Category:People from Nashua, New Hampshire Category:People from Orlando, Florida Category:Soubrettes Category:Ryan Adams Category:21st-century actors

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