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Prednisone

Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids. It is taken by mouth.

Common side effects may include cataracts, bone loss, easy bruising, muscle weakness, and thrush. Other side effects include weight gain, swelling, high blood sugar, increased risk of infection, and psychosis. It is generally considered safe in pregnancy and low doses appear to be safe while the user is breastfeeding. After prolonged use, prednisone must be stopped gradually.

Prednisone is a prodrug and must be converted to prednisolone by the liver before it becomes active. Prednisolone then binds to glucocorticoid receptors, activating them and triggering changes in gene expression.

Prednisone was patented in 1954 and approved for medical use in the United States in 1955. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2021, it was the 28th most commonly prescribed medication in the United States, with more than 19million prescriptions.

Medical uses
Prednisone is used for many different autoimmune diseases and inflammatory conditions, including asthma, gout, COPD, CIDP, rheumatic disorders, allergic disorders, ulcerative colitis and Crohn's disease, granulomatosis with polyangiitis, adrenocortical insufficiency, hypercalcemia due to cancer, thyroiditis, laryngitis, severe tuberculosis, hives, eczema, lipid pneumonitis, pericarditis, multiple sclerosis, nephrotic syndrome, sarcoidosis, to relieve the effects of shingles, lupus, myasthenia gravis, poison oak exposure, Ménière's disease, autoimmune hepatitis, giant cell arteritis, the Herxheimer reaction that is common during the treatment of syphilis, Duchenne muscular dystrophy, uveitis, and as part of a drug regimen to prevent rejection after organ transplant.

Prednisone has also been used in the treatment of migraine headaches and cluster headaches and for severe aphthous ulcer. Prednisone is used as an antitumor drug.

Prednisone is often also prescribed as a form of treatment for sudden sensorineural hearing loss (SSNHL).

Prednisone can be used in the treatment of decompensated heart failure to increase renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. In terms of the mechanism of action for this purpose: prednisone, a glucocorticoid, can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, thereby inducing a potent diuresis.

At high doses it may be used to prevent rejection following organ transplant.

Side effects

Short-term side effects, as with all glucocorticoids, include high blood glucose levels (especially in patients with diabetes mellitus or on other medications that increase blood glucose, such as tacrolimus) and mineralocorticoid effects such as fluid retention. The mineralocorticoid effects of prednisone are minor, which is why it is not used in the management of adrenal insufficiency, unless a more potent mineralocorticoid is administered concomitantly.

It can also cause depression or depressive symptoms and anxiety in some individuals.

Long-term side effects include Cushing's syndrome, steroid dementia syndrome, truncal weight gain, glaucoma and cataracts, diabetes mellitus type 2, and depression upon dose reduction or cessation. Long-term steroids can also increase the risk of osteoporosis, but research has found that few of these people were taking medications to protect bones. Prednisone also results in leukocytosis.

Major
Source:

 * Steroid myopathy
 * Increased blood sugar for individuals with diabetes
 * Difficulty in regulating emotion
 * Difficulty in maintaining linear thinking
 * Weight gain due to increased appetite
 * Immunosuppression
 * Corticosteroid-induced lipodystrophy (moon face, central obesity)
 * Depression, mania, psychosis, or other psychiatric symptoms
 * Unusual fatigue or weakness
 * Mental confusion
 * Memory and attention dysfunction (steroid dementia syndrome)
 * Muscle atrophy
 * Blurred vision
 * Abdominal pain
 * Peptic ulcer
 * Painful hips or shoulders
 * Steroid-induced osteoporosis
 * Stretch marks
 * Osteonecrosis – same as avascular necrosis
 * Insomnia
 * Severe joint pain
 * Cataracts or glaucoma
 * Anxiety
 * Black stool
 * Stomach pain or bloating
 * Severe swelling
 * Mouth sores or dry mouth
 * Avascular necrosis
 * Hepatic steatosis
 * Hiccups and burping
 * Weakening and breakage of tendons

Minor
Source:

 * Nervousness
 * Acne
 * Skin rash
 * Appetite gain
 * Hyperactivity
 * Increased thirst
 * Frequent urination
 * Diarrhea
 * Reduced intestinal flora
 * Leg pain/cramps
 * Sensitive teeth
 * Headache
 * Induced vomiting

Dependency
Adrenal suppression will begin to occur if prednisone is taken for longer than seven days. Eventually, this may cause the body to temporarily lose the ability to manufacture natural corticosteroids (especially cortisol), which results in dependence on prednisone. For this reason, prednisone should not be abruptly stopped if taken for more than seven days; instead, the dosage should be gradually reduced. This weaning process may be over a few days if the course of prednisone was short but may take weeks or months if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addisonian crisis. For those on chronic therapy, alternate-day dosing may preserve adrenal function and thereby reduce side effects.

Glucocorticoids act to inhibit feedback of both the hypothalamus, decreasing corticotropin-releasing hormone (CRH), and corticotrophs in the anterior pituitary gland, decreasing the amount of adrenocorticotropic hormone (ACTH). For this reason, glucocorticoid analogue drugs such as prednisone down-regulate the natural synthesis of glucocorticoids. This mechanism leads to dependence in a short time and can be dangerous if medications are withdrawn too quickly. The body must have time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again.

Prednisone may start to result in the suppression of the hypothalamic–pituitary–adrenal (HPA) axis if used at doses 7–10 mg or higher for several weeks. This is approximately equal to the amount of endogenous cortisol produced by the body every day. As such, the HPA axis starts to become suppressed and atrophy. If this occurs the patient should be tapered off prednisone slowly to give the adrenal gland enough time to regain its function and endogenous production of steroids.

Withdrawal
The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:

 * received more than 40 mg prednisone (or equivalent) daily for more than one week
 * been given repeat doses in the evening
 * received more than three weeks of treatment
 * recently received repeated courses (particularly if taken for longer than three weeks)
 * taken a short course within one year of stopping long-term therapy
 * other possible causes of adrenal suppression

Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and who have received treatment for three weeks or less and who are not included in the patient groups described above.

During corticosteroid withdrawal, the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.

Pharmacology
Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties. Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone.

Pharmacokinetics
Prednisone is absorbed in the gastrointestinal tract and has a half-life of 2–3 hours. it has a volume of distribution of 0.4–1 L/kg. The drug is cleared by hepatic metabolism using cytochrome P450 enzymes. Metabolites are excreted in the bile and urine.

Lodotra
"Lodotra" is the brand name of an oral formulation, which releases prednisone four hours after ingestion. It is indicated for rheumatoid arthritis with morning stiffness. Taken at 10 p.m., it releases the drug at around 2 a.m. The plasmic peak level is reached at 4 a.m., which is considered to be the optimal time for relieving morning stiffness. The drug was approved in the European Union, in January 2009.

Industry
The pharmaceutical industry uses prednisone tablets for the calibration of dissolution testing equipment according to the United States Pharmacopeia (USP).

Chemistry
Prednisone is a synthetic pregnane corticosteroid and derivative of cortisone and is also known as δ1-cortisone or 1,2-dehydrocortisone or as 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione.

History
The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile. The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation, by Arthur Nobile and coworkers. They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone.

The enhanced adrenocorticoid activity of these compounds over cortisone and hydrocortisone was demonstrated in mice.

Prednisone and prednisolone were introduced in 1955 by Schering and Upjohn, under the brand names Meticorten and Delta-Cortef, respectively.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Prednisone


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Newton Falls

Newton Falls may refer to:

 * Newton Falls, Ohio
 * Newton Falls, New York
 * Newton Lower Falls, Massachusetts
 * Newton Upper Falls, Massachusetts

title: Newton Falls


text: User talk:193.173.106.62

title: User talk:193.173.106.62


text:
User:Conrad Leviston~enwiki

 * My current projects on Wikipedia

title: User:Conrad Leviston~enwiki


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Hydrocortisone

Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD. It is the treatment of choice for adrenocortical insufficiency. It can be given by mouth, topically, or by injection. Stopping treatment after long-term use should be done slowly.

Side effects may include mood changes, increased risk of infection, and edema (swelling). With long-term use common side effects include osteoporosis, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections). It is unclear if it is safe for use during pregnancy. Hydrocortisone is a glucocorticoid and works as an anti-inflammatory and by immune suppression.

Hydrocortisone was patented in 1936 and approved for medical use in 1941. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2021, it was the 192nd most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses
Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an adrenal crisis. It may also be injected into inflamed joints resulting from diseases such as gout.

It may be used topically for allergic rashes, eczema, psoriasis, itching and other inflammatory skin conditions. Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only.

It may also be used rectally in suppositories to relieve the swelling, itch, and irritation in haemorrhoids.

It may be used as an acetate form (hydrocortisone acetate), which has slightly different pharmacokinetics and pharmacodynamics.

Pharmacodynamics
Hydrocortisone is a corticosteroid, acting specifically as both a glucocorticoid and as a mineralocorticoid. That is, it is an agonist of the glucocorticoid and mineralocorticoid receptors.

Hydrocortisone has low potency relative to synthetic corticosteroids. Compared to hydrocortisone, prednisolone is about 4times as potent and dexamethasone about 40times as potent in terms of anti-inflammatory effect. Prednisolone can also be used as cortisol replacement, and at replacement dose levels (rather than anti-inflammatory levels), prednisolone is about 8times more potent than cortisol. The equivalent doses and relative potencies of hydrocortisone compared to various other synthetic corticosteroids have also been reviewed and summarized.

The endogenous production rate of cortisol is approximately 5.7 to 9.9mg/m2 per day, which corresponds to an oral hydrocortisone dose of approximately 15 to 20mg/day (for a 70-kg person). One review described daily cortisol production of 10mg in healthy volunteers and reported that daily cortisol production could increase up to 400mg in conditions of severe stress (e.g., surgery).

The total and/or free concentrations of cortisol/hydrocortisone required for various glucocorticoid effects have been determined.

Absorption
The bioavailability of oral hydrocortisone is about 96% ± 20% (SD). The pharmacokinetics of hydrocortisone are non-linear. The peak level of oral hydrocortisone is 15.3 ± 2.9 (SD) μg/L per 1mg dose. The time to peak concentrations of oral hydrocortisone is 1.2 ± 0.4 (SD) hours.

The topical percutaneous absorption of hydrocortisone varies widely depending on experimental circumstances and has been reported to range from 0.5 to 14.9% in different studies. Some skin application sites, like the scrotum and vulva, absorb hydrocortisone much more efficiently than other application sites, like the forearm. In one study, the amount of hydrocortisone absorbed ranged from 0.2% to 36.2% depending on the application site, with the ball of the foot having the lowest absorption and the scrotum having the highest absorption. The absorption of hydrocortisone by the vulva has ranged from 4.4 to 8.1%, relative to 1.3 to 2.8% for the arm, in different studies and subjects.

Distribution
Most cortisol in the blood (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and serum albumin. A pharmacokinetic review stated that 92% ± 2% (SD) (92–93%) of hydrocortisone is plasma protein-bound. Free cortisol passes easily through cellular membranes. Inside cells it interacts with corticosteroid receptors.

Metabolism
Hydrocortisone is metabolized by 11β-hydroxysteroid dehydrogenases (11β-HSDs) into cortisone, an inactive metabolite. It is additionally 5α-, 5β-, and 3α-reduced into dihydrocortisols, dihydrocortisones, tetrahydrocortisols, and tetrahydrocortisones.

Elimination
The elimination half-life of hydrocortisone ranges from about 1.2 to 2.0 (SD) hours, with an average of around 1.5hours, regardless of oral versus parenteral administration. The duration of action of systemic hydrocortisone has been listed as 8 to 12hours.

Chemistry
Hydrocortisone, also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a naturally occurring pregnane steroid. A variety of hydrocortisone esters exist and have been marketed for medical use.

Legal status
In March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Efmody, intended for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older. The applicant for this medicinal product is Diurnal Europe BV. Hydrocortisone (Efmody) was approved for medical use in the European Union, in May 2021, for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older.

Anti-competitive practices
In the UK, the Competition and Markets Authority (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and Actavis plc had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "generic" rather than branded products and thereby escape price controls until eventually other companies entered the market. Auden and Actavis overcharged the UK's National Health Service for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of competition law.

COVID-19
Hydrocortisone was found to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo.

title: Hydrocortisone


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Roddy Doyle

Roddy Doyle (born Roderick Doyle, 8 May 1958) is an Irish novelist, dramatist and screenwriter. He is the author of eleven novels for adults, eight books for children, seven plays and screenplays, and dozens of short stories. Several of his books have been made into films, beginning with The Commitments in 1991. Doyle's work is set primarily in Ireland, especially working-class Dublin, and is notable for its heavy use of dialogue written in slang and Irish English dialect. Doyle was awarded the Booker Prize in 1993 for his novel Paddy Clarke Ha Ha Ha.

Personal life
Doyle was born in Dublin and grew up in Kilbarrack, in a middle-class family. His mother, Ita (née Bolger) was a first cousin of the short story writer Maeve Brennan.

In addition to teaching, Doyle, along with Seán Love, established a creative writing centre, "Fighting Words", which opened in Dublin in January 2009. It was inspired by a visit to his friend Dave Eggers' 826 Valencia project in San Francisco. He has also engaged in local causes, including signing a petition supporting journalist Suzanne Breen, who faced gaol for refusing to divulge her sources in court, and joining a protest against an attempt by Dublin City Council to construct 9 ft-high barriers which would interfere with one of his favourite views.

In 1989, Doyle married Belinda Moller. She is the granddaughter of former Irish President Erskine Childers. They have three children; Rory, Jack and Kate.

Doyle is an atheist.

Education
Doyle attended University College Dublin, where he studied English and geography, and graduated with a BA in 1979. He went on to complete a Higher Diploma in Education (HDipEd) in 1980. He spent several years as an English and geography teacher before becoming a full-time writer in 1993.

Work
Doyle's writing is marked by heavy use of dialogue between characters, with little description or exposition. His work is largely set in Ireland, with a focus on the lives of working-class Dubliners. Themes range from domestic and personal concerns to larger questions of Irish history. His personal notes and workbooks reside at the National Library of Ireland.

Novels for adults
Doyle's first three novels, The Commitments (1987), The Snapper (1990) and The Van (1991) compose The Barrytown Trilogy, a trilogy centred on the Rabbitte family. All three novels were made into successful films.

The Commitments is about a group of Dublin teenagers, led by Jimmy Rabbitte Jr., who decide to form a soul band in the tradition of Wilson Pickett. The novel was made into a film in 1991. The Snapper, made into a film in 1993, focuses on Jimmy's sister, Sharon, who becomes pregnant. She is determined to have the child but refuses to reveal the father's identity to her family. In The Van, which was shortlisted for the 1991 Booker Prize and made into a film in 1996, Jimmy Sr. is laid off, as is his friend Bimbo; the two buy a used fish and chips van and they go into business for themselves.

In 1993, Doyle published Paddy Clarke Ha Ha Ha, winner of the 1993 Booker Prize, which showed the world as described, understood and misunderstood by a ten-year-old Dubliner living in 1968.

Doyle's next novel dealt with darker themes. The Woman Who Walked into Doors, published in 1996, is the story of a battered wife, Paula Spencer, who was introduced in his 1994 television series Family, and is narrated by her. Despite her husband's increasingly violent behaviour, Paula defends him, using the classic excuse "I walked into a door" to explain her bruises. Ten years later, the protagonist returned in Paula Spencer, published in 2006.

Doyle's most recent trilogy of adult novels is The Last Roundup series, which follows the adventures of protagonist Henry Smart through several decades. A Star Called Henry (published 1999) is the first book in the series, and tells the story of Henry Smart, an IRA volunteer and 1916 Easter Rebellion fighter, from his birth in Dublin to his adulthood when he becomes a father. Oh, Play That Thing! (2004) continues Henry's story in 1924 America, beginning in the Lower East Side of New York City, where he catches the attention of local mobsters by hiring kids to carry his sandwich boards. He also goes to Chicago where he becomes a business partner with Louis Armstrong. The title is taken from a phrase that is shouted in one of Armstrong's songs, "Dippermouth Blues". In the final novel in the trilogy, The Dead Republic (published 2010), Henry collaborates on writing the script for a Hollywood film. He returns to Ireland and is offered work as the caretaker in a school when circumstances lead to him re-establishing his link with the IRA.

Doyle frequently posts short comic dialogues on his Facebook page which are implied to be between two older men in a pub, often relating to current events in Ireland (such as the 2015 marriage referendum ) and further afield. These developed into the novella Two Pints (2012). Other recent works are The Guts (2013), which continues the story of the Rabbitte family from the Barrytown Trilogy, focusing on a 48-year-old Jimmy Rabbite and his diagnosis of bowel cancer and Two More Pints (2014).

Novels for children
Doyle has also written many novels for children, including the "Rover Adventures" series, which includes The Giggler Treatment (2000), Rover Saves Christmas (2001), and The Meanwhile Adventures (2004).

Other children's books include Wilderness (2007), Her Mother's Face (2008), and A Greyhound of a Girl (2011).

Plays, screenplays, short stories and non-fiction
Doyle is also a prolific dramatist, composing four plays and two screenplays. His plays with the Passion Machine Theatre Company include Brownbread (1987) and War (1989), directed by Paul Mercier with set and costume design by Anne Gately. Later plays include The Woman Who Walked into Doors (2003); and a rewrite of The Playboy of the Western World (2007) with Bisi Adigun. This latter play was the subject of litigation about copyright which ended with the Abbey Theatre agreeing to pay Adigun €600,000.

Screenplays include the television screenplay for Family (1994), which was a BBC/RTÉ serial and the forerunner of the 1996 novel The Woman Who Walked into Doors. Doyle also authored When Brendan Met Trudy (2000), which is a romance about a timid schoolteacher (Brendan) and a free-spirited thief (Trudy).

Doyle has written many short stories, several of which have been published in The New Yorker; they have also been compiled in two collections. The Deportees and Other Stories was published in 2007, while the collection Bullfighting was published in 2011. Doyle's story "New Boy" was adapted into a 2008 Academy Award-nominated short film directed by Steph Green.

Rory and Ita (2002) is a work of non-fiction about Doyle's parents, based on interviews with them.

The Commitments was adapted by Doyle for a musical which began in the West End in 2013.

Two Pints (2017) was produced by the Abbey Theatre initially in pubs and later in the theatre itself.

In 2018 the Gate Theatre commissioned Doyle to write a stage adaptation of The Snapper. The show was directed by Róisín McBrinn and was revived in 2019.

Awards and honours

 * 1991 Booker Prize shortlist for The Van
 * 1991 BAFTA Award (Best Adapted Screenplay) for The Commitments
 * 1993 Booker Prize for Paddy Clarke Ha Ha Ha
 * 2003 Royal Society of Literature Fellow
 * 2009 Irish PEN Award
 * 2011 French Literary Award ("Prix Littéraire des Jeunes Européens") for The Snapper
 * 2013 Bord Gáis Energy Irish Book Awards (Novel of the Year) for The Guts
 * 2015 Honorary Doctor of Laws (LLD) from University of Dundee
 * 2021 Dalkey Literary Awards, Shortlist

In popular culture
In the television series Father Ted, the character Father Dougal McGuire's unusual sudden use of (mild) profanities (such as saying "I wouldn't know, Ted, you big bollocks!") is blamed on his having "been reading those Roddy Doyle books again".

Novels

 * Smile (2017)
 * Charlie Savage (2019)
 * Love (2020)

 * The Barrytown Pentalogy
 * The Commitments (1987, 1991 film)
 * The Snapper (1990, 1993 film)
 * The Van (1991) ; 1996 film)
 * Paddy Clarke Ha Ha Ha (1993)
 * The Guts (2013)
 * Paula Spencer novels
 * The Woman Who Walked into Doors (1996)
 * Paula Spencer (2006)
 * The Women Behind The Door (2024)
 * The Last Roundup
 * A Star Called Henry (1999)
 * Oh, Play That Thing! (2004)
 * The Dead Republic (2010)

Short fiction

 * Collections
 * The Deportees and Other Stories, September 2007.
 * Bullfighting, April 2011.
 * Life Without Children: Stories (2021)
 * Stories

 * "The Slave" (2000)
 * "Teaching" (2007)
 * "The Dog" (2007)
 * "Bullfighting" (2008)
 * "The Child" (2004)
 * "Sleep" (2008).
 * "The Bandstand" (2009)
 * "Brilliant" (2011)

 * Not Just for Christmas (1999) (part of the Open Door Series of novellas for adult literacy)
 * Mad Weekend (2006) (part of the Open Door Series)
 * Two Pints (2012)
 * Two More Pints (2014)
 * Two for the Road (2019)
 * Dead Man Talking (2015) (part of the Quick Reads Initiative)

Plays

 * Brownbread (1987)
 * War (1989)
 * Guess Who's Coming for the Dinner? (2001)
 * The Woman Who Walked into Doors (2003)
 * Rewrite of The Playboy of the Western World (2007) with Bisi Adigun
 * Two Pints (2017)
 * The Snapper (2018)

Screenplays

 * The Commitments (1991)
 * The Snapper (1993)
 * Family (1994)
 * The Van (1996)
 * When Brendan Met Trudy (2000)
 * New Boy (2008)
 * Rosie (2018)

Children's books

 * Wilderness (2007)
 * Her Mother's Face (2008)
 * A Greyhound of a Girl (2011)
 * Brilliant
 * The "Rover Adventures" series
 * The Giggler Treatment (2000)
 * Rover Saves Christmas (2001)
 * The Meanwhile Adventures (2004)
 * Rover and the Big Fat Baby (2016)

Non-fiction

 * Rory and Ita (2002) – about Doyle's parents
 * The Second Half (2014) – memoirs of Roy Keane

title: Roddy Doyle


text:
Hillah

Hillah (ٱلْحِلَّة al-Ḥillah), also spelled Hilla, is a city in central Iraq on the Hilla branch of the Euphrates River, 100 km south of Baghdad. The population was estimated to be about 455,700 in 2018. It is the capital of Babylon Province and is located adjacent to the ancient city of Babylon, and close to the ancient cities of Borsippa and Kish. It is situated in a predominantly agricultural region which is extensively irrigated with water provided by the Hilla canal, producing a wide range of crops, fruit and textiles. Its name may be derived from the word "beauty" in Arabic. The river runs in the middle of the town, and it is surrounded by date palm trees and other forms of arid vegetation, reducing the harmful effects of dust and desert wind.

The city was once a major center of Islamic scholarship and education. The tomb of the Abrahamic prophet Ezekiel is reputed to be located in a nearby village, Al Kifl.

It became a major administrative centre during the rule of the Ottoman and British Empires. In the 19th century, the Hilla branch of the Euphrates started to silt up and much agricultural land was lost to drought, but this process was reversed by the construction of the Hindiya Barrage in 1911–1913, which diverted water from the deeper Hindiya branch of the Euphrates into the Hilla canal. It saw heavy fighting in 1920 during an uprising against the British, when 300 men of the Manchester Regiment were apparently defeated in the city.

Babylon
Hillah is located near the ruins of ancient Babylon. It is likely that Babylon was founded in the third millennium BC and rose to prominence over the next thousand years. By the 18th century BC the city was the centre of the empire of Hammurabi. Various empires controlled Babylon over the following centuries. Babylon briefly regained independence during the Neo-Babylonian empire towards the end of the 7th century BC, most notably under the reign of king Nebuchadnezzar II, but came under Persian occupation in the 6th century BC.

The ruins of Babylon have suffered greatly due to looting and destructive policies. Parts of Nebuchadnezzar's palace and some of the old city walls still remain. Saddam Hussein commissioned a restoration of ancient Babylon on part of the site. A modern palace was restored on Nebuchadnezzar ancient palace. A reconstruction of the Ishtar Gate is displayed in the Pergamon Museum in Berlin.

Birth of Hillah
In the 10th century, the town of Al Jami'ayn was founded on the eastern bank of the Euphrates. The location of that town is in modern-day Hillah now. In 1101 AD a new town was founded near Al Jami'ayn. Bricks were taken from Babylon to build houses and so Hillah expanded. During the 18th century, the town became an administrative center in the Ottoman Empire. In the 19th century, the flow in the al-Hillah stream decreased, and that led to worsening conditions for agriculture, which affected them greatly. To solve the problem, al-Hindiya Barrage was built.

2003 US invasion
Hillah was the scene of relatively heavy fighting in the 2003 invasion of Iraq on and around April 1, 2003. Iraqi casualties from the Medina Division of the Republican Guard were unknown but casualties reached in the several hundreds for the United States Army's 2-70th Armor. Following the invasion, 1st Battalion 4th Marines had its headquarters at the abandoned Tariq Pistol Factory for 6 months in 2003.

Shortly after the invasion a mass grave site was reported by locals to be in the area around Hillah. Local citizens and members of ORHA, and NMCB-15 (Naval Mobile Construction Battalion) worked together to exhume thousands of Iraqis who had been killed by Iraq's security forces during the uprising against the government in 1991.

The 1st Marine Division had established a base at one of Saddam Hussein's palaces about one mile north of Hillah. The 372nd Military Police Company had performed law and order and Iraqi Police training in the city from June 2003 to October 2003 prior to moving on to Abu Ghraib prison. The city was part of the Polish military zone during the occupation of Iraq.

After the initial invasion, Hilla was relatively peaceful, but it then became the scene of numerous bomb attacks.
 * In February, 2004, insurgents tried but failed to blow up a camp run by Hungarian troops with truck bombs.
 * February 28, 2005 saw the deadliest single insurgent attack up till then, when a car bomb killed 125 people outside a medical clinic.
 * On May 30, 2005, two suicide bombers killed 31, and wounded 108, Shia police.
 * On September 30, 2005, a car bomb exploded in a vegetable market in Hilla, killing 10 and wounding 30 others.
 * On January 2, 2007, at least 73 people were killed and more than 160 were injured when two suicide bombers blew up themselves at a gathering of Shia militias.
 * On February 1, 2007, a pair of suicide bombers detonated explosives among shoppers at a crowded outdoor market, killing at least 45 people and wounding approximately 150.
 * On March 6, 2007, 114 people were killed and at least 147 people were wounded in two car bomb attacks targeting Shia pilgrims.
 * On May 10, 2010, a series of three to four suicide car bombs at the 'State Company for Textile Industries' in the city killed a total of 45 people and left 140 wounded.
 * On March 6, 2016, a truck bomb hit a military checkpoint in Hillah, killing at least 60 people and wounding more than 70. The Islamic State of Iraq and the Levant (ISIL) claimed responsibility for the bombing.

Climate
Hillah has a hot desert climate (BWh) in the Köppen–Geiger climate classification system. Most rain falls in the winter. The average annual temperature in Hillah is 23.1 °C. About 114 mm of precipitation falls annually.

Geology and natural resources
A detailed scientific study at the University of Babylon proved that Babil province is rich with natural untapped oil, gas and minerals of economic and industrial rocks and sediments of rivers and groundwater that can be exploited to intensify studies, geophysical surveys and mining.

Health
Babil governorate has ten hospitals with 1,200 beds. At the beginning of 2005, the local health department announced some plans to build two hospitals with 50 beds each near Al-Khifil and Al-Shomaly. Major hospitals in Hillah, will also receive major renovations. Staff master plan is to raise the level of training of personnel in the field of nursing and re-construction of new health centers across the province.

Hillah contains four major government hospitals and they are: Hillah General Teaching Hospital, Babylon Hospital for Women and Children, Merjan Teaching Hospital, and Al Noor Hospital for Children.

Since 2008, Hillah has hosted an annual medical conference under the slogan "Babylon .. cultural capital of Iraq .. the future of medicine in scientific research". The conference offers a number of scientific presentations that address the medical health and education in the country and projects to support health and medical research in the future. There is also an exhibition of modern medical devices and electric vehicles for people with disabilities, in addition to medicines and treatments. The bast medical laboratory is called Al-Zahawi medical lab. and it is run by the well-known Dr. Anmar D. Ghazalah

Culture
Hillah has a rich cultural history and is widely mentioned in history books, literature, geography, and biographies. The single most famous medieval Shia theologian, Allamah Jamāl ad-Dīn al-Hasan al-Hilli was a native of Hillah. It was chosen as the cultural capital of Iraq in 2008 because of its large cultural gatherings and art galleries, as well as the many talents in all fields of culture and art, particularly poetry, writing, music and vocals.

Many well known Iraqi writers have written about the city, including: Mr. Abdul-Razzaq al-Husseini, Abd al-Qadir al-Zahawi, Mohammad Mehdi Aljawahiri, Rusafi, Sahtia AlHasri, Dr. Fadel Aljamali, Thi Alnun Ayoub, Dr Ali Jawad Tahir, and Ahmad al-Safi al-Najafi.

Many writers, poets, and artists have also come from Hillah, including: Dheyaa Hamio, Saifuddin Al-Hilly, Mohammed Mahdi Albasir, Ali Jawad Tahir, archaeologists Ahmed Sosa, Taha Baqir, and Ahmed Saeed.

Other medieval scholars native to Hillah are Muhaqqiq al-Hilli and Ibn Tawus.

Education
The Ottomans established modern schools, including the school Al-Rashidiya where material was taught in Turkish. The first elementary school in Hillah was Madrasat Al-Sharqia, which was founded in 1918 with one class and twenty students. It was located in the top floor of the Grand Mosque and the first director of it was Mr. Abdul Mahdi al-Hilali. Later the school moved to a building on the Shatt al-Hilla with four classes, but this school was not stable because the majority of students leave these schools to study at the seminary. The first secondary school in Hillah, established in 1927, was Al-Hillah Secondary School. Another school was Moderiat Alm'arif, founded in year 1931.

University education in Hillah started with the founding of the Institute of Management in 1976 and the foundation of the Department of Technology and Management Branch Stores. In 1980 it was called the Technical Institute; today it is called the Technical Institute in Babylon and includes the following fields: scientific (civil and space and electrical and electronic devices, computers and mechanics, machinery and equipment), administrative (accounting, management, and computer systems), and medical (community health and nursing). In 1959 the Technical Institute established a project Musayyib that included these disciplines: technological (Irrigation and mechanics, machinery and equipment), administrative (accounting, warehouse management), and agricultural (plant production, soil and land reclamation, machinery and agricultural equipment, and production of life). Starting in 1991, the University of Babylon offers education in fine arts, law, engineering, science, education, medicine, management, economy, literature, agriculture, science for girls dentistry, veterinary medicine, and nursing. The university includes several scientific centers: Center for Studies Babylonian Center, documents and studies Hillah, electronic calculators, Teaching Methods Development Center, and Continuing Education Center. The province of Babylon contains five universities: Babylon University, Alqasim Green University (introduced in 2012 in Al-Qasim), Al-Nahrain University, Almostaqbal University College, and Hillah University College.

Babylon ruins
Located just 5 km (3.1 mi) north of the city of Hillah, Babylon was a marveled city of the ancient world, especially under the rule of king Nebuchadnezzar (605–562 BC). It was the capital of the Neo-Babylonian Empire and its walls and hanging gardens were considered one of the seven wonders of the world.

Kish ruins (Tel Alahamr)
Kish is located 13 km (8 mi) from city of Hillah and 6 km (3.7 mi) east of the ancient city of Babylon. The ruins including the ziggurat "Inner Cdermh", a ziggurat structure of "Baba deer", god of war.

Alberes
Alberes is situated south of Hillah, approximately 24 km (14.9 mi) away. It has a tower found between Hillah and Al-Khifil. Its current name is a distortion of the name Old Babylonian "بورسيا" (which is now a newspaper) and its Sumerian meaning is "sword of the sea", because it was located on the Ghadeer edge along the banks of the Sea of Najaf.

title: Hillah


text: User talk:212.219.234.97

title: User talk:212.219.234.97


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IXI Limited

IXI Limited was a British software company that developed and marketed windowing products for Unix, supporting all the popular Unix platforms of the time. Founded in 1987, it was based in Cambridge. The product it was most known for was X.desktop, a desktop environment graphical user interface built on the X Window System. IXI was acquired by the Santa Cruz Operation (SCO) in February 1993.

Origins in the Cambridge hi-tech cluster
In the beginning of the 1970s, the so-called Cambridge hi-tech cluster became the site of a network of new firms in the rapidly growing computer field, many of which featured founders and employees who had studied at the University of Cambridge. And in particular, as an article in the journal Regional Studies has noted, IXI was one of many companies started by founders or employees or those in the nexus of Cambridge-based Acorn Computers, the most noted of which is ARM Holdings.

IXI founder Ray Anderson was a graduate of the university who had become director of research and development at Torch Computers, a computer systems firm located in the Cambridge area that was most known for making peripherals for the BBC Micro made by Acorn. Torch built workstations among its products, and also had a license agreement to provide NeXT with aspects of workstation technology.

In the end, Torch was not successful, but its work inspired Anderson to carry the idea on.

Independent company

IXI Limited was founded by Ray Anderson in 1987 as a private company. Anderson originally had a former colleague as a partner, but the partner decided a start-up was too uncertain and pulled out within a year or so. Anderson found funding for IXI from sources in the United Kingdom, Germany, Austria, and Japan, but avoiding US investors as his prior experiences had made him leery of them.

As one former SCO UK employee has succinctly summarised, "IXI specialised in software that ran on Unix and made Unix easier to use." In particular, a goal was to make Unix workstations as easy to use as a Macintosh, which would allow non-technical people to use such platforms. IXI's best-known product was X.desktop, an X11-based graphical desktop environment with finder and file management capabilities for Unix systems. There was an opportunity for such a product because when the X11 version of the X Window System came out in 1987, it made a point of separation of mechanism and policy (indeed, it has been termed a canonical example of that design philosophy). Consequently, while it supported the ability to provide such things, it contained no specification for application user-interface design such as buttons, menus, or window title-bar styles, nor did it provide a standard window manager, file manager, or desktop.

The initial unreleased version of X.desktop, intended as a proof of concept, was programmed to the Xlib level; the first version that saw public release, 1.3, was based on the Xt library and Athena widgets. The X.desktop product then came to be based on Motif toolkit from the Open Software Foundation (OSF), a switch that happened in 1989 with release 2.0.

The first customers for IXI came in the financial industry, who were early adopters of Unix-based workstations. These were generally American companies, with sales to the Japanese market coming soon thereafter. Indeed, IXI has been characterized as an example of a "global start-up", in that instead of following the expected route for a start-up of establishing a domestic business first and then slowly expanding into international operations, it worked to establish an international business right away.

A crucial part of IXI's standard was to capitalize on standards and thus defeat competitors who were based more upon proprietary solutions. This later paid benefits when X.desktop proved cost-effective to internationalize to other languages.

X.desktop was sold as both shrink-wrapped software for end users, at a price of $495 for any platform. But it was also sold on an OEM basis to system manufacturers. Early OEM customers included Locus Computing Corporation, BiiN, Olivetti, Acorn Computers and Compaq. An OEM sale was to IBM in 1989 for its RS/6000 and IBM AIX proved to be a turning point in IXI's fortunes. The SCO OpenDesktop product was another early adopter, and was another key usage of the product for the company. OEM customers gained by 1990 included NCR Corporation, Dell, Uniplex, Parallel Systems International, and Network Computing Devices.

As an InfoWorld article from 1990 stated, the ability to have OEM customers was a key factor in IXI Limited being successful. Part of this success was due to X.desktop coming with a customization toolkit that allowed system manufacturers to modify the appearance and functionality of the desktop environment to match their needs. The customization took the form not just of customizing icons, but the ability to tie icons to arbitrary series of commands.

The X.desktop product was stated as being ported to, and sold on, over a dozen different Unix variants. And as a paper published for a 1994 USENIX conference detailed, versions of X.desktop were actually built for over 30 different Unix platforms. The ability to maintain the portability of the X.desktop code base became a key factor in IXI's success with the product.

The primary competitor of X.desktop was the Looking Glass product from the American company Visix Software, Inc. Trade publications ran comparisons of the two desktop environments, and detailed cases where one beat another for an account.

Eventually over a million instances of X.desktop were in use. In 1992 IXI released Deskworks, a suite of productivity tools that included such things as a clock, a text editor, a mail client, a time management tool, and the like.

For 1992, IXI Ltd had revenues of about $6 million. By early 1993, the firm employed around 50 people, and in addition to its Cambridge headquarters, it also had offices in San Ramon, California, in the US and in Tokyo in Japan. According to a later article in MoneyWeek, by this time IXI had some 70% of the workstation market.

Acquisition by SCO
IXI was acquired by the Santa Cruz Operation (SCO), in an announcement made on 25 February 1993. Terms of the purchase were not publicly disclosed, but did involve an exchange of stock. As mentioned, SCO had previously licensed IXI technology in its operating system product, and there were existing ties between the engineering and marketing functions of both companies. Anderson later said of his motivation to sell, that having gotten a 70% share, "getting the remaining 30% of the market would have required heavy reinvestment. I felt ready to move on."

The IXI brand continued on for the next couple of years as a relatively independent subsidiary of SCO. The announcement in mid-1993 by several major Unix vendors of the Common Desktop Environment (CDE) project posed a competitive threat to X.desktop, but it took two years of further development until CDE actually came out.

Several new products were introduced during this time. IXI Panorama, introduced about a month after the acquisition, was a Motif-based window manager, that could run with or without X.desktop; it had the ability to plot and manage a virtual space much greater than the physical space of the monitor itself. Panorama was extended in March 1994 with IXI Mosaic, reflecting the incorporation of the first popular web browser, Mosaic, into the SCO Global Access product, a modified version of SCO Open Desktop that served as an Internet gateway. In doing this, SCO and IXI put out the world's first commercial web browser based on Mosaic, and, according to Anderson, the first commercial web browser of any kind.

IXI Premier Motif was a product that came from IXI taking the OSF-released Motif source code and applying a set of bug fixes and enhancements and then porting it such that it would give identical behavior across platforms. IXI also offered some twenty different Motif training courses for users. The IXI Wintif product, which became available in 1994, built further upon Premier Motif to create a version of Motif that had the look-and-feel of Microsoft Windows 3.1 and thus would enable Windows users to operate Unix applications without confusion or need for additional training. A later version extended this capability to Windows 95.

Then in 1995, the IXI business unit of SCO was merged with another SCO acquisition, the Leeds-based Visionware, to form IXI Visionware. (IXI had previously collaborated with Visionware, going back to 1988 when the Visionware technologies were first being developed within Systime Computers Ltd. ) Later in 1995 the merged business unit was subsumed more fully into its parent and became the Client Integration Division of SCO, which put out products from both former companies under the "Vision"-branded family name. This included the creation of VisionFS, an SMB server that could do network installs of the Windows components of the Vision family from a Unix server with minimal user configuration needed. This division then developed and released the Tarantella terminal services application in 1997 and that became the core of Tarantella, Inc. in 2001. Tarantella, Inc. struggled and following company-wide layoffs, the Cambridge development site closed in the summer of 2003.

Fates
The X.desktop code gradually went into maintenance mode as X.desktop OEM providers migrated to CDE and many end-users abandoned Unix-based workstations altogether and switched to Wintel platforms. Ray Anderson left SCO after several years there, and in 1999 founded Bango plc, a mobile commerce company based in Cambridge.

title: IXI Limited


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Anterograde amnesia

In neurology, anterograde amnesia is the inability to create new memories after an event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories created prior to the event are lost while new memories can still be created. Both can occur together in the same patient. To a large degree, anterograde amnesia remains a mysterious ailment because the precise mechanism of storing memories is not yet well understood, although it is known that the regions of the brain involved are certain sites in the temporal cortex, especially in the hippocampus and nearby subcortical regions.

Signs and symptoms
People with anterograde amnesic syndromes may present widely varying degrees of forgetfulness. Some with severe cases have a combined form of anterograde and retrograde amnesia, sometimes called global amnesia.

In the case of drug-induced amnesia, it may be short-lived and patients can recover from it. In another case, which has been studied extensively since the early 1970s, patients often have permanent damage, although some recovery is possible, depending on the nature of the pathophysiology. Usually, some capacity for learning remains, although it may be very elementary. In cases of pure anterograde amnesia, patients have recollections of events prior to the injury, but cannot recall day-to-day information or new facts presented to them after the injury occurred.

In most cases of anterograde amnesia, patients lose declarative memory, or the recollection of facts, but they retain nondeclarative memory, often called procedural memory. For instance, they are able to remember, and in some cases learn how to do things, such as talking on the phone or riding a bicycle, but they may not remember what they had eaten earlier that day for lunch. One extensively studied anterograde amnesiac patient, codenamed H.M., demonstrated that despite his amnesia preventing him from learning new declarative information, procedural memory consolidation was still possible, albeit severely reduced in power. He, along with other patients with anterograde amnesia, were given the same maze to complete day after day.

Despite having no memory of having completed the maze the day before, unconscious practice of completing the same maze over and over reduced the amount of time needed to complete it in subsequent trials. From these results, Corkin et al. concluded despite having no declarative memory (i.e. no conscious memory of completing the maze exists), the patients still had a working procedural memory (learning done unconsciously through practice). This supports the notion that declarative and procedural memory are consolidated in different areas of the brain. Patients have a diminished ability to remember the temporal context in which objects were presented. Certain authors claim the deficit in temporal context memory is more significant than the deficit in the semantic learning ability (described below).

Causes
This disorder is usually acquired in one of four ways: One cause is benzodiazepine drugs such as midazolam, flunitrazepam, lorazepam, temazepam, nitrazepam, triazolam, clonazepam, alprazolam, diazepam, and nimetazepam. All of these are known to have powerful amnesic effects. This has also been recorded in non-benzodiazepine sedatives or "z-drugs" which act on the same set of receptors, such as zolpidem (also known as Ambien), eszopiclone (also known as Lunesta), and zopiclone (also known by brand names Imovane and Zimovane). A second cause is a traumatic brain injury in which damage is usually done to the hippocampus or surrounding cortices. It may also be caused by PTSD, a shocking event, or an emotional disorder. Illness, though much rarer, can also cause anterograde amnesia if it causes encephalitis, which is the inflammation of brain tissue. There are several types of encephalitis: one such is herpes simplex encephalitis (HSV), which, if left untreated, can lead to neurological deterioration. How HSV gains access to the brain is unknown. The virus shows a distinct predilection for certain parts of the brain. Initially, it is present in the limbic cortices. It may then spread to the adjacent frontal and temporal lobes. Damage to specific areas can result in reduced or eliminated ability to encode new explicit memories, giving rise to anterograde amnesia.

Patients with anterograde amnesia may have episodic, semantic, or both types of explicit memory impaired for events after the trauma that caused the amnesia. This suggests that memory consolidation for different types of memory takes place in different regions of the brain. Despite this, current knowledge on human memory is still insufficient to "map out" the wiring of a human brain to discover which parts of which lobe are responsible for the various episodic and semantic knowledge within a person's memory.

Amnesia is seen in patients who, for the reason of preventing another more serious disorder, have parts of their brains known to be involved in memory circuits removed, the most notable of which is known as the medial temporal lobe (MTL) memory system, described below. Patients with seizures originating in the MTL may have either side or both structures removed (there is one structure per hemisphere). Patients with tumors who undergo surgery will often sustain damage to these structures, as is described in a case below. Damage to any part of this system, including the hippocampus and surrounding cortices, results in amnesic syndromes. This is why after a stroke people have a chance of developing cognitive deficits that result in anterograde amnesia, since strokes can involve the temporal lobe in the temporal cortex, and the temporal cortex houses the hippocampus.

Anterograde amnesia can be the first clinical sign that Alzheimer's disease is developing within the brain. Although later the complications can be much more widespread and strongly impair cognitive processes, at the initial stage of Alzheimer's the changes observed can be restricted to anterograde amnesia and a mild deficit in retaining newly learnt sequences. This is explained by the fact that the disease is initiated within the medial temporal lobe and first affects the entorhinal cortex that directly sends and receives information from the hippocampal formation.

Alcohol intoxication
Anterograde amnesia can also be caused by alcohol intoxication, a phenomenon commonly known as a blackout. Studies show rapid rises in blood alcohol concentration over a short period of time severely impair or in some cases completely block the brain's ability to transfer short-term memories created during the period of intoxication to long-term memory for storage and later retrieval. Such rapid rises are caused by drinking large amounts of alcohol in short periods of time, especially on an empty stomach, as the dilution of alcohol by food slows the absorption of alcohol. Alcohol-related anterograde amnesia is directly related to the rate of consumption of alcohol, and is often associated with binge drinking, and not just the total amount of alcohol consumed in a drinking episode.

Test subjects have been found not to experience amnesia when drinking slowly, despite being heavily intoxicated by the end of the experiment. When alcohol is consumed at a rapid rate, the point at which most healthy people's long-term memory creation starts to fail usually occurs at approximately 0.20% BAC, but can be reached as low as 0.14% BAC for infrequent drinkers. The exact duration of these blackout periods is hard to determine, because most people fall asleep before they black out. Upon reaching sobriety, usually after waking, long-term memory creation is completely restored.

Chronic alcoholism often leads to a thiamine (vitamin B1) deficiency in the brain, causing Korsakoff's syndrome, a neurological disorder which is generally preceded by an acute neurological condition known as Wernicke's encephalopathy (WE). The memory impairment that is pathognomonic to Korsakoff's syndrome predominantly affects the declarative memory, leaving non-declarative memory that is often procedural in nature relatively intact. The disproportionate severity in anterograde episodic memory processes in contrast to other cognitive processes is what differentiates Korsakoff syndrome from other conditions such as alcohol-related dementia. Evidence for the preservation of certain memory processes in the presence of severe anterograde episodic memory serve as an experimental paradigm to investigate the components of human memory.

Pathophysiology
The pathophysiology of anterograde amnesic syndromes varies with the extent of damage and the regions of the brain that were damaged. The most well-described regions indicated in this disorder are the medial temporal lobe (MTL), basal forebrain, and fornix. Beyond the details described below, the precise process of how we remember – on a micro scale – remains a mystery. Neuropsychologists and scientists are still not in total agreement over whether forgetting is due to faulty encoding, accelerated forgetting, or faulty retrieval, although a great deal of data seem to point to the encoding hypothesis.

Neuroscientists are in disagreement about the length of time involved in memory consolidation. Though most researchers, including Hasselmo et al., have found the consolidation process is spread out over several hours before transitioning from a fragile to a more permanent state, others, including Brown et al., posits that memory consolidation can take months or even years in a drawn-out process of consolidation and reinforcement. Further research into the length of time of memory consolidation will shed more light on why anterograde amnesia sometimes affects some memories gained after the event(s) that caused the amnesia, but does not affect other such memories.

Medial temporal lobe
The MTL memory system includes the hippocampal formation (CA fields, dentate gyrus, subicular complex), perirhinal, entorhinal, and parahippocampal cortices. It is known to be important for the storage and processing of declarative memory, which allows for factual recall. It is also known to communicate with the neocortex in the establishment and maintenance of long-term memories, although its known functions are independent of long-term memory. Nondeclarative memory, on the other hand, which allows for the performance of different skills and habits, is not part of the MTL memory system. Most data point to a "division of labor" among the parts of this system, although this is still being debated and is described in detail below.

In animal models, researchers have shown monkeys with damage to both the hippocampus and its adjacent cortical regions were more severely impaired in terms of anterograde amnesia than monkeys with damage localized to hippocampal structures. However, conflicting data in another primate study points to the observation that the amount of tissue damaged does not necessarily correlate with the severity of the memory loss. The data does not explain the dichotomy that exists in the MTL memory system between episodic memory and semantic memory (described below).

An important finding in amnesic patients with MTL damage is the impairment of memory in all sensory modalities – sound, touch, smell, taste, and sight. This reflects the fact that the MTL is a processor for all of the sensory modalities, and helps store these kind of thoughts into memory. In addition, subjects can often remember how to perform relatively simple tasks immediately, in the order of 10 seconds. When the task becomes more difficult, even on the same time scale, subjects tend to forget. This demonstrates the difficulty of separating procedural memory tasks from declarative memory; some elements of declarative memory may be used in learning procedural tasks.

MTL amnesic patients with localized damage to the hippocampus retain other perceptual abilities, such as the ability to intelligently function in society, to make conversation, to make one's bed, etc. Anterograde amnesics without combined retrograde disorders (localized damage to the MTL system) have memories prior to the traumatic event. For this reason, the MTL is not the storage place of all memories; other regions in the brain also store memories. The key is the MTL is responsible for the learning of new materials.

Other memory systems
A limited number of cases have been described in which patients with damage to other parts of the brain acquired anterograde amnesia. Easton and Parker observed damage to either the hippocampus or the surrounding cortices does not seem to result in severe amnesia in primate models. They suggested damage to the hippocampus and surrounding structures alone does not explain the amnesia they saw in patients, or increasing damage does not correlate with the degree of impairment.

The data does not explain the dichotomy that exists in the MTL memory system between episodic and semantic memory. To demonstrate their hypothesis, they used a primate model with damage to the basal forebrain. They proposed that the disruption of neurons that project from the basal forebrain to the MTL are responsible for some of the impairment in anterograde amnesia. Easton and Parker also reported MRI scans of patients with severe anterograde amnesia showed damage beyond to cortical areas around the hippocampus and amygdala (a region of brain involved in emotions) and to surrounding white matter. White matter in the brain consists of axons, long projections of neuronal cell bodies.

Another case described the onset of anterograde amnesia as a result of cell death in the fornix, another structure that carries information from the hippocampus to the structures of the limbic system and the diencephalon. The patient in this case did not show any disconnection syndrome, which is unexpected since the structures involved divide the brain hemispheres. Both sides of her brain were able to communicate. Instead, she showed signs of amnesia. The final diagnosis was made by MRI. This particular amnesic syndrome is difficult to diagnose and is often misdiagnosed by physicians as an acute psychiatric disorder.

Reorganization of memory
When there is damage to just one side of the MTL, there is opportunity for normal functioning or near-normal function for memories. Neuroplasticity describes the ability of the cortex to remap when necessary. Remapping can occur in cases like the one above and with time the patient can recover and become more skilled at memory retention. A case report describing a patient who had two lobectomies – in the first, doctors removed part of her right MTL first because of seizures originating from the region, and later her left because she developed a tumor – demonstrates this.

This case is unique because it is the only one in which both sides of the MTL were removed at different times. The authors observed that the patient was able to recover some ability to learn when she had only one MTL, but observed the deterioration of function when both sides of the MTL were affected. The reorganization of brain function for epileptic patients has had limited investigation, but imaging results show that it may occur.

Rehabilitation
Approaches used to treat those with anterograde amnesia often use interventions which focus on compensatory techniques, such as beepers, written notes, diaries or through intensive training programs involving the active participation of the individual concerned, along with their supporting network of family and friends. In this perspective, environmental adaptation techniques are used, such as the compensatory technique education to training (exercise), organizational strategies, visual imagery and verbal labeling. Other techniques are used in rehabilitation, such as implicit tasks, speech and mnemotechnic methods.

So far, it has been proven that education techniques of compensatory strategies for memory disorders are effective in individuals with minor traumatic brain injuries. In moderately or severely injured individuals, effective interventions are those appealing to external aids, such as reminders in order to facilitate particular knowledge or skill acquisition. In reality, orientation techniques are also considered; their purpose is to enhance orientation using stimulation and repetition of the basic orientation information. These techniques are regularly applied in populations of patients primarily presenting dementia and head injuries.

Episodic versus semantic memory
As described above, patients with anterograde amnesia have a wide range of forgetfulness. Declarative memory can be further subdivided into episodic and semantic memory. Episodic memory is the recollection of autobiographical information with a temporal and/or spatial context, whereas semantic memory involves recall of factual information with no such association (language, history, geography, etc.). In a case study of a girl who developed anterograde amnesia during childhood, it was determined that the patient ("C.L.") retained semantic memory while having an extreme impairment of episodic memory.

One patient, known by the codename "Gene", was involved in a motorcycle accident that damaged significant portions of his frontal and temporal lobes, including his left hippocampus. As a result, he could not remember any specific episode in his life, such as a train derailment near his house. However, his semantic memory was intact; he remembered that he owned a car and two motorcycles, and he could even remember the names of his classmates in a school photograph.

In stark contrast, a woman whose temporal lobes were damaged in the front due to encephalitis lost her semantic memory. She lost her memory of many simple words, historical events, and other trivial information categorized under semantic memory. Her episodic memory was left intact. She could recall episodes such as her wedding and her father's death with great detail.

Vicari et al. describe that it remains unclear whether neural circuits involved in semantic and episodic memory overlap partially or completely, and this case seems to suggest that the two systems are independent. Both of the patient's hippocampal and diencephalic structures on the right and left sides were disconnected. When C.L. came to Vicari et al.'s office, her chief complaint was forgetfulness involving both semantic and episodic memory. After administering a battery of neuropsychological tests, Vicari determined that C.L. performed well in tests of visual naming and sentence comprehension, visual-spatial ability, and "general semantic knowledge about the world". They also noted an improved vocabulary and general knowledge base after 18 months.

C.L.'s episodic memory, on the other hand, was far below expectations: She could not retain daily events, where she had gone on vacation, the names of places she had been, and other such information. However, this study and others like it are susceptible to subjectivity, since it is not always possible to clearly distinguish between episodic and semantic memory. For this reason, the topic remains controversial and debated.

Familiarity and the fractionation of memory
The right hippocampus is clearly necessary for familiarity in spatial tasks, whereas the left hippocampus is necessary for familiarity-based recollection in verbal tasks. Some researchers claim the hippocampus is important for the retrieval of memories, whereas adjacent cortical regions can support familiarity-based memories. These memory decisions are made based on matching already-existing memories, before the onset of pathology, to the current situation. According to Gilboa et al., patients with localized hippocampal damage can score well on a test if it is based on familiarity.

Poreh et al. describe a case study of patient A.D., whose damage to the fornix rendered the hippocampus useless, but spared adjacent cortical areas – a fairly rare injury. When the patient was given a test with something with which he had some familiarity, the patient was able to score well. In general, A.D. had severely impaired episodic memory, but had some ability to learn semantic knowledge. Other studies show animals with similar injuries can recognize objects with which they are familiar, but, when the objects are presented in an unexpected context, they do not score well on recognition tests.

Islands of memory
Patients with anterograde amnesia have trouble recalling new information and new autobiographical events, but the data is less consistent in regard to the latter. Medveds and Hirst recorded the presence of islands of memory – detailed accounts – that were described by such patients. The island memories were a combination of semantic and episodic memories. The researchers recorded patients giving long narratives with a fair amount of detail that resembled memories that the patients had prior to the trauma. The appearance of islands of memory could have something to do with the functioning of adjacent cortical areas and the neocortex. In addition, the researchers suspect that the amygdala played a role in the narratives.

Notable cases
The most famous case reported is that of patient Henry Molaison, known as H.M., in March 1953. Molaison's chief complaint was the persistence of severe seizures and therefore had a bilateral lobectomy, with both his medial temporal lobes removed. As a result, Molaison had bilateral damage to both the hippocampal formation and the perirhinal cortex. Molaison had average intelligence and perceptual ability, and a decent vocabulary. However, he could not learn new words or remember things that had happened more than a few minutes earlier. He could remember anything from his childhood. If the memory was created from before his lobectomy, he still had the ability to retrieve it and remember. However, he was able to learn some new skills. He was the first well-documented case of severe anterograde amnesia, and was studied until his death in 2008.

A similar case involved Clive Wearing, an accomplished musicologist who contracted a cold sore virus that attacked his brain, causing herpes simplex encephalitis. As a result, Wearing developed both anterograde and retrograde amnesia. He has little memory of what happened before the virus struck him in 1985, and cannot learn new declarative knowledge after the virus struck him. As a result of anterograde amnesia, Wearing repeatedly "wakes up" every day, usually in 30-second intervals. He has a history of repeatedly recording these moments of waking up in his journal (e.g., On Sept 2, 2013, I woke up, etc. etc.) and crossing out prior entries, as if the other moments of waking up were not real. His episodic memory is nonfunctional, so he does not consciously recall having woken up 30 seconds prior.

Clive is often elated to see his wife, as if he has not seen her for a while. Despite this, Wearing maintained his ability to play the piano and conduct choirs. This case is significant because it demonstrates declarative and procedural memory are separate. Therefore, despite anterograde amnesia preventing Wearing from learning new bits of information that can be explained in words (declarative memory), and preventing him from storing new memories of events or episodes (also part of declarative memory), he has little trouble in retaining his musical abilities (procedural memory), though he has no conscious memory of having learned music.

Another case in the literature is Eugene Pauly, known as E.P., a severely amnesic patient, owing to viral encephalitis, who was able to learn three-word sentences. He performed better on consecutive tests over a 12-week period, of 24 study sessions. However, when asked how confident he was about the answers, his confidence did not appear to increase. Bayley and Squire proposed his learning was similar to the process required by procedural memory tasks. E.P. could not get the answers right when one word in the three-word sentence was changed, or the order of words was changed. His ability to answer correctly, thus, became more of a "habit". Bayley and Squire claim the learning may have happened in the neocortex, and it happened without the conscious knowledge of E.P. They hypothesized the information may be acquired directly by the neocortex (to which the hippocampus projects) when there is repetition. This case illustrates the difficulty in separating procedural from declarative tasks. This adds another dimension to the complexity of anterograde amnesia.

In film
Notable examples include Lucy Whitmore in 50 First Dates, Joseph Gordon-Levitt in The Lookout, Kaori Fujimiya in One Week Friends, Chihiro Shindou in Ef: A Fairy Tale of the Two, Christine Lucas in Before I Go to Sleep, Gus in Remember Sunday.

Christopher Nolan's psychological crime film Memento (2000) contains a distinguished depiction of anterograde amnesia, in that the memory-impaired protagonist Leonard Shelby is trying to identify and kill the man who raped and murdered his wife, and does so through a system of writing crucial details related to the search on his body and on the blank spaces of Polaroid photographs. Mental health experts have described Memento as one of the most accurate depictions of amnesia in film history, an accuracy that was enhanced by the film's fragmented, non-linear structure that mimics the protagonist's memory problems.

Dory, the happy-go-lucky Regal Blue Tang from Finding Nemo (2003) and Finding Dory (2016), suffers from anterograde amnesia. While Dory forgets conversations within minutes of having them, she never quite forgets who she is, or the fact that she has short-term memory loss, and can therefore explain her bizarre behavior to those around her.

Ghajini (2008), a Hindi language film from India based on Memento, in which the main protagonist Sanjay Singhania played by Amir Khan has short-term memory loss, a variant of amnesia. In the film he is the one behind Ghajini, the killer of his fiancée Kalpana. In the TV series Perception, an episode revolved around a crime victim with this condition. The main character Latro in Gene Wolfe's novels Soldier of the Mist, and the anime characters Vash the Stampede from Trigun and Index and Tōma from A Certain Magical Index had both retrograde and anterograde amnesia. The disorder has also been portrayed in music by English musician the Caretaker in Theoretically Pure Anterograde Amnesia (2005) and Additional Amnesiac Memories (2006).

In the 1964 film 36 Hours, Rod Taylor plays Nazi Major Walter Gerber, a psychiatrist who has developed an effective method for treating German soldiers with what is now known as PTSD – and for painlessly extracting information from Allied prisoners. The technique involves convincing patients that years have passed, the war is over, and that they have anterograde amnesia, which supposedly can be cured with talk therapy. A few days before D-Day, U.S. Army Major Jeff Pike (James Garner) is drugged, kidnapped and taken to what appears to be a hospital run by American Occupation Forces, where his appearance is altered overnight. Pike knows that the invasion is aimed at Normandy, not Pas de Calais, as the Nazi high command expects. He buys Gerber's explanation of anterograde amnesia – using the double doors of a wardrobe as illustration – and speaks casually of Normandy. Salt in a papercut alerts him to the horrible truth, and the drama proceeds from there.

In television
In the episode "Pimemento" of Brooklyn Nine-Nine, Adrian Pimento develops an artificial form of anterograde amnesia after being drugged by his therapist, which is the main plot point of the episode.

In the Star Trek: Enterprise episode "Twilight", Jonathan Archer develops anterograde amnesia.

In books
In the 2011 the light novel Danganronpa Zero, the protagonist and "Ultimate Analyst" Ryoko Otonashi has anterograde amnesia as a result of "The Tragedy". She keeps note of her memories by writing into a journal at all times and using her speedreading to keep herself up to date. Seen to be her boyfriend and "Ultimate Neurologist" Yasuke Matsuda, Ryoko witnesses a murder committed by Junko Enoshima, before being mistaken for wanted murderer and Tragedy perpetrator Izuru Kamukura by the "Ultimate Bodyguard" Madarai octuplets. After teaming up with the perverted "Ultimate Secret Agent" Yuto Kamishiro in an attempt to discover the perpetrator behind the Tragedy, Ryoko learns that she herself was personally involved in the event as the true Junko. The Junko she met was her non-identical twin sister Mukuro Ikusaba, with whom she shared Matsuda as a boyfriend, attempting to trigger her memories, which Matsuda had been suppressing on Junko's own request, both to clear her of suspicion in the events of the Tragedy, attempt to cure her depression, and a test to wipe the memories of others. Attempting to subdue Ryoko, Matsuda accidentally restores her memories of being Junko and being fatally stabbed, before wishing Junko success in her planned actions with Izuru and Mukuro: a collapsing world society and launching a "killing game".

In the 2003 novel The Housekeeper and the Professor by Yōko Ogawa, the Professor suffers from anteretograde amnesia following a traffic accident and is unable to store memories for more than eighty minutes.

In video games
In the 2016 video game Phoenix Wright: Ace Attorney – Spirit of Justice, the character Sorin Sprocket is eventually revealed to have anterograde amnesia, which he developed after unintentionally causing a car accident which killed his sister. This causes his memories to completely reset every time he wakes up from sleeping, to the day after this accident. This depiction is notable for demonstrating the relationship issues that arise between Sorin and his fiancée, Ellen Wyatt, as a result of this disorder, most noticeably with how Sorin's feelings towards her comes across as distant and cold.

As the storyline continues, the player comes to uncover that Sorin in fact deeply loves his fiancée, and is able to maintain this love despite his disorder, but in fact feels a sense of guilt over the fact that he has to constantly remind himself of the fact that this love exists inside of him every day, due to his disorder. It is also noticeable that it depicts how Sorin deals with his disorder, by keeping a journal where he writes down every detail of every day after his sister's death. He carries this journal around everywhere he goes as a substitute to his memories, and uses what is written in the notebook to become aware each time he wakes up of the fact that he has this condition, what the current date apparently is, and everything important that have apparently occurred on every day since he first developed the condition.

The episode also deals with legal issues concerning the disorder, when it is debated during Ellen Wyatt's trial as to whether Sorin's journal can be considered a proper substitution to his memories for the sake of viable witness testimony. Dangers imposed by this also come into play when it is revealed that a page in Sorin's journal had been altered by someone, which causes him to go into a mental collapse, afraid that any of his other memories and thoughts could also have arisen from someone else's manipulation.

Other sources

 * Weingartner, H., Parker, E. Memory Consolidation: Psychobiology of Cognition. Hillsdale: Lawrence Erlbaum Associates, Inc., Publishers, 1984.
 * Weingartner, H., Parker, E. Memory Consolidation: Psychobiology of Cognition. Hillsdale: Lawrence Erlbaum Associates, Inc., Publishers, 1984.

title: Anterograde amnesia


text:
Basiliximab

Basiliximab, sold under the brand name Simulect, is a monoclonal antibody used to prevent rejection in kidney transplants. It is a chimeric mouse-human monoclonal antibody to the α chain (CD25) of the IL-2 receptor of T cells. It is used in combination with other medicines used to prevent organ rejection.

The most common side effects (seen in more than 20% of patients) include constipation, urinary tract infections (infection of the structures that carry urine), pain, nausea (feeling sick), peripheral oedema (swelling), hypertension (high blood pressure), anemia (low red blood cell counts), headache, hyperkalaemia (high blood potassium levels), hypercholesterolaemia (high blood cholesterol levels), surgical wound complication, weight increase, increased serum creatinine (a marker of kidney problems), hypophosphataemia (low blood phosphate levels), diarrhea and upper respiratory tract infection (colds).

Basiliximab was approved for medical use in the United States and in the European Union in 1998.

Medical uses
Basiliximab is indicated for the prophylaxis of acute organ rejection in de-novo allogeneic renal transplantation. It is to be used concomitantly with ciclosporin for microemulsion- and corticosteroid-based immunosuppression, in people with panel reactive antibodies less than 80%, or in a triple maintenance immunosuppressive regimen containing ciclosporin for microemulsion, corticosteroids and either azathioprine or mycophenolate mofetil.

Basiliximab is an immunosuppressant agent used to prevent immediate transplant rejection in people who are receiving kidney transplants, in combination with other agents. It has been reported that some cases of lichen planus have been successfully treated with basiliximab as an alternative therapy to cyclosporin. No short-term side effects have been reported.

Mechanism of action
Basiliximab competes with IL-2 to bind to the alpha chain subunit of the IL2 receptor on the surface of the activated T lymphocytes and thus prevents the receptor from signaling. This prevents T cells from replicating and also from activating B cells, which are responsible for the production of antibodies, which would bind to the transplanted organ and stimulate an immune response against the transplant.

Chemistry
It is a chimeric CD25 monoclonal antibody of the IgG1 isotype.

History
It is a Novartis product and was approved by the Food and Drug Administration (FDA) in 1998.

title: Basiliximab


text:
Daclizumab

Daclizumab (trade name Zinbryta) is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells.

In March 2018, it was voluntarily withdrawn from the market by Biogen and Abbvie after reports of autoimmune encephalitis in Europe.

Medical uses
Daclizumab was used to treat adults with relapsing forms of multiple sclerosis. It is administered subcutaneously.

In clinical trials, decreases of 45% in annualized relapse rate have been reported, as well as a 41% reduction in the proportion of patients who relapsed, and a 54% reduction in the number of new lesions. A 2013 Cochrane systematic review concluded that there was insufficient evidence to determine the efficacy of daclizumab relative to placebo in people with relapsing-remitting MS and, prior to its being discontinued, the need to investigate longer lengths of treatment and follow-up.

Discontinued use
Daclizumab was approved and used to prevent acute rejection of kidney transplant, along with cyclosporine and corticosteroids. For that indication, side effects with a frequency of at least 10% included sleeplessness, tremor, headache, arterial hypertension, dyspnoea, gastrointestinal side effects and oedema. In rare cases, the drug could cause severe anaphylaxis.

Contraindications
In the US, daclizumab (while approved) was contraindicated in people with liver impairment, including significantly elevated liver enzymes (ALT, AST) and autoimmune hepatitis.

The European Medicines Agency (EMA) originally approved the drug without any contraindications apart from known hypersensitivity, but required Biogen to implement a hepatic risk management guide for physicians. In July 2017, the EMA has issued a provisional contraindication for patients with pre-existing liver disease or liver impairment. The marketing authorisation was withdrawn in the EU on 27 March 2018. An EMA review concluded that the medicine poses a risk of serious and potentially fatal immune reactions affecting the brain, liver and other organs.

Adverse effects
In clinical trials for MS, there were no treatment-related deaths or increased risk of cancer; side effects that occurred more frequently with daclizumab versus interferon included infections (65% versus 57%), skin rashes (37% versus 19%) and liver complications (approximately 18% versus 12%).

Interactions
As an antibody, daclizumab is expected to have a very low potential for pharmacokinetic interactions with other drugs.

Mechanism of action
Daclizumab blocks IL-2 receptors containing the alpha subunit (CD25), which include the high-affinity receptors. Medium-affinity receptors, on the other hand, consist of two beta subunits (CD122) and are not affected by daclizumab. While the exact mechanism is unknown, the net effect is a reduction of T-cell responses and expansion of CD56bright natural killer cells.

Pharmacokinetics
After subcutaneous injection of a single dose, daclizumab has a bioavailability of about 90% and reaches highest blood plasma levels after 5 to 7 days. Given every four weeks, steady state concentrations are found after the fourth dose. It is expected that daclizumab, like other antibodies, is degraded by proteases to peptides and finally amino acids, and that it does not interact with cytochrome P450 liver enzymes.

The biological half-life is 21 days. Patients who developed antibodies against daclizumab eliminated it 19% faster.

History
Daclizumab was created by scientists at PDL BioPharma (called "Protein Design Labs" at that time) by humanizing the mouse mAb called anti-Tac, which targets CD25, the IL-2 receptor α chain; it blocks the interaction of IL-2 with the IL-2 receptor and prevents activation of T cells. Anti-Tac had been discovered by Thomas A. Waldmann, M.D., chief of the Metabolism Branch at the National Cancer Institute and his team, and they had conducted animal studies and a small clinical trial of anti-Tac in people with T-cell leukemia, with promising results, but people quickly developed their own antibodies rejecting the mouse protein; Waldman, and his colleagues then approached Protein Design Labs to humanize the antibody. PDL and the NIH scientists then approached Roche, a leader in transplant medicine development, to get the drug developed and approved, as PDL didn't have the resources to actually bring the product to market. In March 2018 the drug was removed from the market worldwide.

In December 1997 daclizumab was approved by the FDA for use in preventing acute rejection of kidney transplants, in combination with ciclosporin and corticosteroids; it was the first humanized antibody approved anywhere in the world. At launch, the average wholesale price for the drug was estimated to be $6,800 for five doses and it was estimated that annual sales would be between $100 million and $250 million within five years of the launch and it was thought that the drug's use would be expanded for use in other organ transplants. It was approved in Europe in 1999.

PDL began clinical trials of daclizumab on its own, and in September 2004 after the drug had shown promise in a Phase II trial, PDL and Roche agreed to expand their relationship to include codevelopment of daclizumab for asthma and other respiratory conditions. In August 2005, PDL and Biogen Idec agreed to collaborate to develop daclizumab in indications outside the fields of organ rejection and respiratory disease. In November 2005 Roche and PDL agreed to try to develop a formulation of daclizumab that would be useful as a subcutaneous injection for longterm maintenance in organ transplant. The next year Roche and PDL announced that the collaboration for all indications was ending, and in 2009 it announced that it was discontinuing Zenapax worldwide "in view of available alternative treatments and the diminishing market demand" and "not due to any safety issue."

in 2008 PDL spun out its active development programs into a company called Facet Biotech and development of daclizumab for multiple sclerosis and the partnership with Biogen was included in that spinout. In 2009 Biogen attempted a hostile buy out of Facet for $350M; Facet rejected that offer and was purchased by Abbvie for $450 million in cash the next year. In May 2016 the FDA approved daclizumab for the treatment of relapsing multiple sclerosis in adults in 2016 under the trade name Zinbryta, with requirements for postmarketing studies and to submit a formal Risk Evaluation and Mitigation Strategy.

Research
Daclizumab has been studied in a small clinical trial of people with birdshot chorioretinopathy.

title: Daclizumab