Anthony Irwin Kornheiser (; born July 13, 1948) is an American television sports talk show host and former sportswriter and columnist. Kornheiser is best known for his endeavors in three forms of media: as a writer for The Washington Post from 1979 to 2008, as a co-host of ESPN's Emmy Award-winning sports debate show Pardon the Interruption since 2001, and as the host of The Tony Kornheiser Show, a radio show and podcast. Longtime ESPN executive John Walsh once declared that "in the history of sports media, [Kornheiser] is the most multitalented person ever."

Early life
Kornheiser was born in New York City and raised in nearby Lynbrook. He was the only child of Estelle (née Rosenthal; 1915–1978) and Ira Kornheiser (1910–2000). His father was a dress cutter. During his youth, Kornheiser spent his summers at Camp Keeyumah in Pennsylvania. One of his counselors was future NCAA and NBA basketball coach Larry Brown. Kornheiser attended George W. Hewlett High School, where he was the sports editor of the school newspaper. He graduated in 1965.

After high school, Kornheiser went to Harpur College (now Binghamton University), where he majored in English literature and began his journalism career at the Colonial News (now called Pipe Dream). He graduated with a Bachelor of Arts in 1970. Kornheiser has frequently spoken positively of his college years. For a brief period of time after college, he worked with children with disabilities.

Print career

Early writing career
Kornheiser began his career in New York City, where he wrote for Newsday between 1970 and 1976. His first work at Newsday consisted of covering high school sports. Kornheiser then moved to The New York Times, where he wrote between 1976 and 1979.

In 1979, George Solomon recruited Kornheiser to join The Washington Post as a general assignment reporter in Style and Sports. In 1980, Kornheiser also authored a profile of Nolan Ryan that served as the cover story for the charter issue of Inside Sports. He became a full-time sports columnist at the Post in 1984. He also began writing columns for the Post's Style Section on November 12, 1989.

In the 1990s, Kornheiser usually wrote three columns per week, which were a Tuesday column and a Thursday column in the Sports Section and a Sunday column (written for a more general audience) in the Style Section. He also started working for ESPN Radio in 1997 and kept his column at the Post. As part of his ESPN Radio contract, Kornheiser wrote columns called "Parting Shots" for ESPN The Magazine between 1998 and 2000.

Writing style
Kornheiser's columns were usually sarcastic with touches of humor. The most distinct style of his columns was that he often used an alter ego in italics to question his points of views for self-deprecation, like "Excuse me, Tony..." At times, he would also use exaggeration for the sake of humor. According to Stephanie Mansfield of Sports Illustrated, Kornheiser was regarded by many as "the wittiest columnist" in American newspapers. Robert Weintraub of the Columbia Journalism Review praised him, in retrospect, for his "blend of beauty and precision." Kornheiser was also capable of being "deadly serious" when need be.

The Bandwagon columns
In 1991, Kornheiser created a string of now-famous Bandwagon columns to describe the Washington Redskins' Super Bowl run that year. He first came up with the idea when the Redskins trounced the Detroit Lions, 45–0, in the opening game of the season. He officially unveiled the first "Bandwagon" column when the team had an undefeated 4–0 record. From then on, the Bandwagon column appeared every Tuesday, celebrating "the fun and hilarity of sports." As the season progressed and the team's performances improved, a growing number of fans read the Bandwagon column in earnest.

When the Redskins advanced to Super Bowl XXVI, Kornheiser and his Post colleagues Jeanne McManus and Norman Chad drove in a 38-foot recreational vehicle decorated as the Bandwagon for a 1,200-mile journey to Minneapolis, Minnesota. Kornheiser later described the Bandwagon columns as "the most fun I ever had as a writer."

Late writing career
In the early 2000s – because of his work on both radio and Pardon the Interruption – Kornheiser stopped writing Style Section columns and only wrote one column a week. His last Style Section column was published on September 30, 2001. Three of his books – Pumping Irony, Bald as I Wanna Be, and I'm Back for More Cash – are compilations of his Style Section columns.

In 2005, Kornheiser started to write short columns called A Few Choice Words with his photo in the Post's Sports Section. These short, sports-related columns appeared on the second page of the Post'''s Sports section and were much shorter than the full-length columns Kornheiser used to write for the paper. This was the first time that the Post displayed a columnist's photo beside his column. He called these short columns "columnettes," writing three per week unless he had other duties. He did not write columns between April 26, 2006, and August 7, 2006, to prepare as an analyst of ESPN's Monday Night Football. Starting August 8, 2006, he wrote columns called Monday Night Diary to describe his adventures on Monday Night Football. His short-column space was later replaced by Dan Steinberg's D.C. Sports Bog.

On May 14, 2008, it was announced that Kornheiser had accepted a buyout from the Post. "I love the paper. They were great to me every day that I was there," he told Reuters. "But I don't do much for the paper anymore." Kornheiser had not written a regular column for the paper's print edition since 2006. However, Kornheiser and Wilbon continued to tape a "Talking Points" mini online TV feature for the Washington Post until June 2, 2009, when an installment termed the final one was posted on the Post's site. In it Wilbon says he thinks there will be further installments while Kornheiser seems certain it is a permanent decision management has made.

On May 20, 2010, Kornheiser said on his radio show that in fact he was fired by the Washington Post, saying "they fired me in a despicable way." On September 11, 2013, Kornheiser repeated his account: "Raju Narisetti fired me from the Washington Post and I hate his guts."

Radio and podcast career

 Radio era
Kornheiser hosted The Tony Kornheiser Show first locally on WTEM – known as Sports Radio 570 – in Washington, D.C. between May 25, 1992, and November 14, 1997. The Kornheiser-led show was part of WTEM's original lineup. The show was then syndicated by ESPN Radio between January 5, 1998, and March 26, 2004. He was back on WTEM locally between November 10, 2004, and April 28, 2006, after which point Kornheiser put the show on hiatus in order to prepare for his duties with Monday Night Football. His show was also carried for a short while by XM Satellite Radio, airing between February 28, 2005 and April 28, 2006.

After completing the 2006 season on Monday Night Football, Kornheiser signed with WTWP, Washington Post Radio, to relaunch his radio show on February 20, 2007. The show aired live from 8:30 a.m. to 10:30 a.m. and was then replayed from 10:30 a.m. to 12:30 p.m. XM Radio carried his show on a thirty-minute delay, from 9 a.m. to 11 a.m., beginning March 5, 2007, on XM Sports Nation, Channel 144. Kornheiser went on hiatus from the show following the June 28, 2007, broadcast because of his Monday Night Football duties. The show was hosted by David Burd and included the same supporting cast. The show was called The Tony Kornheiser Show Starring David Burd during the hiatus.

Kornheiser returned to the show as the full-time host from January 21, 2008, to June 27, 2008, after which point WWWT – the successor to WTWP – declined to renew his contract due to declining ratings. The show aired live from 8:00 a.m. to 10:00 a.m. and was replayed from 2:00 p.m. to 4:00 p.m on WWWT, as well as on XM Sports Nation, XM channel 144 from 8:15 a.m. to 10:00 a.m. He announced during this period in 2008 that he would not be back on the radio until he was done with Monday Night Football.The Tony Kornheiser Show was on the air daily Monday through Friday from 10:00 a.m. to noon on Washington, D.C. radio station WTEM and streamed live on the station's website, ESPN980.com, until June 2016. The show was also available as a podcast. There was originally a 24-hour "podcast delay," a source of many jokes amongst fans and show members alike. The delay ended in 2015, allowing listeners to download episodes a few minutes after the live broadcast.

 Podcast era
On June 2, 2016, Kornheiser announced that his show will be relaunched as a podcast-only show. According to Kornheiser, the reason to do a podcast-only show was to own his content and do the podcast a little closer to his home. However, the show format would still be the same as the radio show, albeit slightly shorter in length. Kornheiser's son, Michael, handled the social media for the podcast and launched a website with information about how to subscribe.

On September 6, 2016, Kornheiser returned from his summer vacation with the first full episode of the new podcast. The first episode was titled "We're Back!!! The Tony Kornheiser Show Returns" and ran for 1 hour and four minutes. Most parts of the old show – including "Old Guy Radio" and the Mailbag – were retained. Gary Braun and Chris Cillizza joined Kornheiser in studio. Michael Wilbon of ESPN and Steve Sands of the Golf Channel were the first guests joining by phone.

The podcast-only show is produced in partnership with sports talent agency IMG and on-demand audio company DGital Media. The podcast is available at 11 a.m. ET via iTunes, Google Play, Spotify, Stitcher, and TuneIn.

Throughout its many iterations, a central quality of the show has been its eagerness to discuss issues other than sports, including news, politics, entertainment, and the idiosyncrasies of modern life. In its early years, the show amassed a large and loyal following that remains to this day. The fans – who refer to themselves as "littles" – have an annual musical convention and use "La Cheeserie" as a catch phrase (in reference to a cheese counter at D.C.-area liquor store Calvert Woodley).

Television career
Kornheiser appeared on a local weekly Washington Redskins TV show during the NFL football season on Washington's Channel 50 in the early 1980s with Pete Wysocki, a popular former Redskins linebacker and local hero, which was televised from a local restaurant/bar in Washington, D.C. called "Champions."

He appeared on ESPN's The Sports Reporters beginning in 1988 and continuing during the 1990s. He sometimes guest-hosted the program when the then-host of the show, Dick Schaap, was away. He was also a panelist on Full Court Press hosted by George Michael on WRC-TV in Washington, D.C. during the NFL off-season until that show was canceled in December 2008 due to budget cuts. He also made a number of appearances on Redskins Report on WRC. He has appeared on numerous other ESPN productions, including SportsCenter, Who's Number One?, and multiple player's/sportspeople's profiles for SportsCentury.

Pardon the InterruptionPardon the Interruption (abbreviated PTI) is a sports television show that airs weekdays on various ESPN TV channels, TSN, BT Sport ESPN, XM, and Sirius satellite radio services, and as a downloadable podcast. On PTI, Kornheiser and co-host Michael Wilbon discuss, and frequently argue over, the top stories of the day in "sports... and other stuff" (as Kornheiser put it in the show's original promo).

Kornheiser's lively segments with Wilbon on the radio and on Full Court Press – which mirrored their actual discussions in the newsroom of The Washington Post – sparked the idea for PTI well before the end of his run at ESPN Radio. The show won a Sports Emmy Award for best Daily Outstanding Studio Show in 2010, 2017, and 2019.

Monday Night Football

When Monday Night Football moved from ABC to ESPN, Kornheiser received and accepted an offer to be a color analyst on Monday Night Football in early 2006.Reinardy and Wanta, p. 5. He was originally passed over in favor of Sunday Night Football commentator Joe Theismann; however, when play-by-play man Al Michaels left ABC to call Sunday Night Football for NBC, Kornheiser was brought in alongside Theismann and new play-by-play announcer Mike Tirico. As such, Kornheiser was part of the broadcast team covering the New Orleans Saints' 23–3 victory over the Atlanta Falcons in the Saints' first game in the Superdome after Hurricane Katrina.

Unlike Wilbon, Kornheiser does most episodes of PTI in-studio due to his self-admitted fear of flying. Prior to joining MNF, his last trips outside of the studio were to cover Super Bowl XXXVI in New Orleans and to attend the NFL owners meetings in Orlando in 2006; Kornheiser both times traveled via train, though returned from the Orlando trip via airplane. On the April 6, 2006 edition of PTI, he expressed his dismay at the amount of travel required for MNF. Though he has mentioned on his radio program that he is taking steps to overcome his aviophobia, he in fact spent a five-week period on the road traveling to mainly western MNF sites, doing PTI via satellite.

Kornheiser returned for a second season of Monday Night Football. On January 9, 2007, Kornheiser told Newsday, "If they would like to have me back, my inclination is that I would like to do it again."

On May 18, 2009, ESPN announced that Kornheiser would be leaving Monday Night Football due to fear of flying. Former Oakland Raiders and Tampa Bay Buccaneers head coach Jon Gruden replaced Kornheiser in the MNF booth.

Entertainment
The 2004–2005 sitcom Listen Up, which aired on CBS, was loosely based on Kornheiser's life. It featured Jason Alexander as Tony Kleinman. The sitcom's material mostly came from Kornheiser's columns (collected in I'm Back for More Cash) that he contributed to the "Style" section of the Washington Post, which took a humorous view of his family life.

Kornheiser had a cameo appearance as a bar patron in a 2015 episode of The Americans.

In June 2016, Kornheiser participated in the roast of political commentator and strategist James Carville.

Restaurant
In January 2017, it was announced that Kornheiser was part of a new ownership group for Chad's (formerly Chadwick's), a bar and restaurant located in the Friendship Heights area of Washington, D.C. The group also included former Maryland basketball coach Gary Williams, TV host Maury Povich, and D.C. businessman and socialite Alan Bubes. Kornheiser is quoted as saying: "Did I always want to be part of a restaurant? No. But now with a podcast and trying to own my own content, the ability to put it on during the mornings or during the day and to have other people use it, that would be fun for me."

In April 2017, Kornheiser announced that Chad's would be renamed Chatter. The new owners made several improvements, including remodeling the interior and adding a podcast studio. Kornheiser began recording episodes of The Tony Kornheiser Show at Chatter on May 1, 2017. Many fans of the show visited the restaurant to listen live.

On June 28, 2019, Kornheiser announced that the podcast would move to a new location after the summer break due to the closure of Chatter.

 Personal life
Kornheiser currently resides in the Chevy Chase neighborhood of Washington, D.C., as well as Rehoboth Beach, Delaware, with his wife Karril.Kornheiser's wife's name is sometimes incorrectly given as "Carol" They have two children, Michael and Elizabeth. Kornheiser is Jewish.

Kornheiser was a member of the Young Democrats club while in high school. As of 1990, Kornheiser was a registered Republican, although he did so because his wife was a registered Democrat and the couple wanted to "receive mailings from both sides." Later, he referred to the decision to register as a Republican as a "mistake." Kornheiser voted for Barack Obama during the 2008 and 2012 presidential elections. During a podcast episode released on January 31, 2017, Kornheiser stated: "I land on the liberal side of the fence almost all the time, certainly on social issues."

Kornheiser has a pronounced fear of flying. He regularly goes to bed early. He can name all fifty U.S. states and their capitals in alphabetical order.

In 2006, Kornheiser revealed that he had skin cancer and had received treatment.

Criticism
 General
While earning a name as a critic of many people and organizations, he has appeared sensitive to criticism directed toward his own work.

Stephen Rodrick wrote for Slate that Kornheiser was allowed by ESPN to argue aimlessly on television and that his Washington Post column was being used to plug side projects rather than gather news from cited sources. Kornheiser called on Slate, owned by the Post's parent company, to fire Rodrick.

After Kornheiser's first game on Monday Night Football, Paul Farhi wrote in The Washington Post that Kornheiser had emphasized the obvious, played third fiddle, and was reminiscent of Dennis Miller "in a bad way." Kornheiser responded during an interview on The Dan Patrick Show on August 15, 2006, saying that Farhi was a "two-bit weasel slug" and his own newspaper had back-stabbed him. His response generated more criticism from media outlets, including the Post. Other criticism came from Toronto Argonauts play-by-play commentator Mike Hogan, who said, "The thing that really bothers me is that Kornheiser doesn't seem to know his place. If you're there for comic relief, that's one thing. But for God's sake, leave the football analysis to guys who actually played the game." Former NFL offensive lineman Mike Schad also criticized Kornheiser, saying that "when people watch a game, they want to learn something. I don't need a guy who's sarcastic or trying to be funny. I love listening to Ron Jaworski on Monday Nights. He played the game and has lots of good insight and Kornheiser just gets in his way."

Mike Golic – an ESPN colleague of Kornheiser's who had expressed skepticism regarding the latter's prospects as an on-air analyst because he was never an athlete – said that Kornheiser's performance on MNF was "fine." Kornheiser's response was, "I just want to wring Golic's neck and hang him up over the back of a shower rod like a duck."

 Controversial remarks
During a Monday Night Football telecast on September 15, 2008, Kornheiser made a comment about a clip of the ESPN Deportes crew's call of a Felix Jones touchdown, saying, "I took high-school Spanish, and that either means 'nobody is going to touch him' or 'could you pick up my dry cleaning in the morning.'" Later in the broadcast, Kornheiser apologized on-air for the remark.

On February 23, 2010, it emerged that ESPN had suspended Kornheiser for two weeks for comments he made on his radio show about fellow high-profile ESPN personality Hannah Storm's wardrobe that day.

In March 2010, Kornheiser commented: "The last time I looked, the roads were made for automobiles...We're going to be dominated as if this was Beijing by hundreds of thousands of bicyclists... They all wear... my God... with the little water bottle in the back and the stupid hats and their shiny shorts. They are the same disgusting poseurs that in the middle of a snowstorm come out with cross-country skiing on your block. Run 'em down... Let them use the right, I'm okay with that. I don't take my car and ride on the sidewalk because I understand that's not for my car... Why do these people think that these roads were built for bicycles?... They dare you to run them down." Cyclist Lance Armstrong replied. "Disgusting, ignorant, foolish. What a complete f-ing idiot." Kornheiser later apologized to Armstrong on-air and offered to go on a bike ride with him.

In June 2010, Green Bay Packer quarterback Aaron Rodgers criticized Kornheiser's performance on Monday Night Football, saying: "He's terrible... I don't think he's funny. I don't think he's insightful. I don't think he knows, really, anything about sports." Rodgers also criticized ESPN analyst Ron Jaworski and other ESPN employees during the interview. Kornheiser responded in an interview by saying: "If he thinks I'm no good, he wouldn't be the first. Or the last," and "I tried to establish some rapport with that. I guess that rapport didn't exist." The two have since reconciled. Kornheiser and Rodgers even played a round of golf together with Barack Obama and Mark Kelly in April 2016.

In October 2015, Kornheiser was interviewing Huffington Post editor Howard Fineman about the conservative movement in Congress when he asked if Tea Party members are "like ISIS trying to establish a caliphate here," which Fineman called a "good analogy" but without the violence.

 Honors
Kornheiser was a finalist for the 1997 Pulitzer Prize for Commentary.

In 2008, Kornheiser was inducted into the National Jewish Sports Hall of Fame.

In 2012, Kornheiser was ranked No. 8 in the list of the 100 most important sports talk radio hosts in America compiled by Talkers Magazine. In 2016, the Tony Kornheiser Show was ranked No. 1 as America's Top 20 Local Sports Midday Shows for 2015 by Barrett Sports Media.

In May 2017, Binghamton University – Kornheiser's alma mater – awarded him an honorary Doctor of Humane Letters.

On July 9, 2017, Kornheiser was inducted into the Washington, D.C. Sports Hall of Fame alongside such notable names as Olympic swimmer Katie Ledecky and former NFL commissioner Paul Tagliabue.

On October 4, 2017, Kornheiser and Michael Wilbon shared the National Press Club's 2017 Fourth Estate Award, which "recognizes journalists who have made significant contributions to the field."

White House visits
On July 12, 2013, Kornheiser, Michael Wilbon and Tony Reali were guests at the White House. After lunch, the trio met in the Oval Office with President Barack Obama. Obama invited Kornheiser and Wilbon to play golf with him the following day, which happened to be Kornheiser's 65th birthday.

Kornheiser also played golf with Obama on a number of other occasions, including in September 2013, June 2014, July 2014, July 2015, April 2016, and May 2016.

Books

References

 Bibliography

External links

  for The Tony Kornheiser Show  for The Tony Kornheiser Show''
@MrTonySays – An unofficial Twitter feed for Tony Kornheiser quotes from TV and Radio. Endorsed by the folks at Pardon The Interruption
TV Guide Bio

1948 births
Living people
American color commentators
American columnists
American sports radio personalities
ESPN people
Harpur College alumni
George W. Hewlett High School alumni
National Football League announcers
People from Lynbrook, New York
The Washington Post people
Sportswriters from New York (state)
Jewish American writers
Binghamton University alumni

Tony Kornheiser


Luis Javier Méndez Moza (Santa Cruz de la Sierra, 12 de julio de 1985) es un exfutbolista boliviano.  Se desempeñaba como defensa.

Clubes

Palmarés

Campeonatos nacionales

Enlaces externos
 Ficha en BDFA

 Ficha en Soccerway

Nacidos en Santa Cruz de la Sierra
Futbolistas de Bolivia
Futbolistas de la selección de fútbol de Bolivia
Futbolistas del Club San José
Futbolistas del Club Deportivo Oriente Petrolero
Futbolistas del Club The Strongest

Luis Méndez


Zvonimir "Zvonko" Vujin (* 28. Juni 1943 in Zrenjanin, Jugoslawien; † 8. Dezember 2019 ebenda) war ein jugoslawischer Amateurboxer im Leichtgewicht (57 bis 60 kg) und Halbweltergewicht (60 bis 63,5 kg). Er wurde 1967 Vize-Europameister und gewann Bronzemedaillen bei den Olympischen Spielen 1968 und 1972.

Boxkarriere
Vujin trainierte im Club "Banat Zrenjanin" und bei der jugoslawischen Nationalmannschaft, für die er 57 Länderkämpfe bestritt. Er wurde 1965, 1966, 1969 und 1972 jeweils Jugoslawischer Meister im Leichtgewicht, 1966 und 1967 Balkanmeister im Leichtgewicht, sowie 1971 auch Balkanmeister im Halbweltergewicht. Darüber hinaus gewann er 1967 im Leichtgewicht die Mittelmeerspiele.

Im Laufe seiner Karriere startete er bei drei Europameisterschaften im Leichtgewicht; 1965 in Berlin verlor er im Viertelfinale gegen den späteren Goldmedaillengewinner Wilikton Barannikow, während er 1967 in Rom, mit Siegen gegen Wolfgang Schmitt, Sven Erik Paulsen und Dieter Dunkel in das Finale kam und dort gegen Józef Grudzień unterlag. 1969 in Bukarest schied er im Viertelfinale gegen den späteren Europameister Calistrat Cuțov aus.

Seine größten Erfolge waren der zweimalige Gewinn einer olympischen Bronzemedaille; 1968 in Mexiko-Stadt schlug er im Leichtgewicht Peter Rieger, Waleri Beloussow und Luis Minami, ehe er im Halbfinale gegen Józef Grudzień ausschied. 1972 in München kam er im Halbweltergewicht mit Siegen gegen Robert Mwakosya, Sodnomyn Gombo und Graham Moughton erneut in das Halbfinale, wo er gegen Ray Seales unterlag.

Tod
Zvonimir Vujin starb am 8. Dezember 2019 im Alter von 76 Jahren in Zrenjanin und wurde im Rahmen einer Gedenkveranstaltung im Rathaus der Stadt verabschiedet. Seine Beisetzung erfolgte am 10. Dezember 2019 am Evangelischen Friedhof in Zrenjanin.

Sonstiges
2021 wurde die Sporthalle von Zrenjanin nach ihm benannt.

Weblinks

Einzelnachweise

Boxer (Jugoslawien)
Mittelmeerspielesieger (Boxen)
Teilnehmer der Mittelmeerspiele 1963
Teilnehmer der Mittelmeerspiele 1967
Olympiateilnehmer (Jugoslawien)
Teilnehmer der Olympischen Sommerspiele 1968
Teilnehmer der Olympischen Sommerspiele 1972
Jugoslawe
Serbe
Geboren 1943
Gestorben 2019
Mann

Zvonimir Vujin


Gefangenenaustausch steht für:
 Agentenaustausch, Austausch von gefangenen Geheimdienstagenten

Siehe auch:

Gefangenenaustausch


The New Archies is an American animated television series and sitcom produced by DIC Animation City, based upon the characters by Archie Comics. The series, originally produced for NBC's Saturday morning schedule and broadcast from September 12 to December 5, 1987, depicted the characters of Archie Andrews, Betty Cooper, Veronica Lodge, Jughead Jones, Reggie Mantle, and other students of Riverdale High School as pre-teens in junior high.

Archie produced an identically named and themed comic book series that ran alongside the animated series.

In the series, Veronica uses the dialect of an archetypal valley girl. In the animated series produced by Filmation and the radio show, she had a southern accent. Dilton Doiley did not appear on The New Archies, and was replaced by an African American child named Eugene. Eugene's girlfriend Amani was also introduced in The New Archies, as was Archie's dog, Red.

Cast
 J. Michael Roncetti as Archie Andrews
 Lisa Coristine as Betty Cooper
 Alyson Court as Veronica Lodge
 Michael Fantini as Jughead Jones
 Sunny Besen Thrasher as Reggie Mantle
 Marvin Goldhar as Mr. Weatherbee
 Colin Waterman as Eugene
 Greg Swanson as Coach
 Karen Burthwright as Amani
 Victor Erdos as Big Moose
 Jazzmin Lausanne as Big Ethel
 Linda Sorenson as Miss Grundy

Episodes
"The Visitor" / "Ballot Box Blues" – September 12, 1987: written by Kimmer Ringwald
"The Last Laugh" / "Thief of Hearts" – September 19, 1987: written by Kimmer Ringwald (The Last Laugh), Jon Cohen (Thief of Hearts)
"I Gotta Be Me or Is It You?" / "Sir Jughead Jones" – September 26, 1987: written by Jon Cohen (I Gotta Be Me or Is It You?), Kimmer Ringwald (Sir Jughead Jones)
"The Awful Truth" / "Jughead Predicts" – October 3, 1987: written by Scott Anderson (The Awful Truth), Eleanor Burian-Mohr and Jack Hanrahan (Jughead Predicts)
"Future Shock" / "Stealing the Show" – October 10, 1987: written by Scott Anderson (Future Shock), Herb Engelhardt (Stealing the Show)
"Hamburger Helpers" / "Goodby Ms. Grundy" – October 17, 1987: written by Pat Allee and Ben Hurst (Hamburger Helpers), Herb Engelhardt (Goodby Ms. Grundy)
"Red to the Rescue" / "Jughead the Jinx" – October 24, 1987: written by Eleanor Burian-Mohr and Jack Hanrahan (Red to the Rescue), Pat Allee and Ben Hurst (Jughead the Jinx)
"Telegraph, Telephone, Tell Reggie" / "Wooden It Be Loverly" – October 31, 1987: written by Eleanor Burian-Mohr and Jack Hanrahan
"I Was a 12 Year Old Werewolf" / "The Prince of Riverdale" – November 7, 1987: written by Dennis O'Flaherty
"Loose Lips Stops Slips" / "A Change of Minds" – November 14, 1987: written by Eleanor Burian-Mohr and Jack Hanrahan (Loose Lips Stops Slips), Gary Greenfield (A Change of Minds)
"Incredible Shrinking Archie" / "Gunk for Gold" – November 21, 1987: written by Gary Greenfield (Incredible Shrinking Archie), Eleanor Burian-Mohr and Jack Hanrahan (Gunk for Gold)
"Jughead's Millions" / "Making of Mr. Righteous" – November 28, 1987: written by Gary Greenfield (Jughead's Millions), Pat Allee and Ben Hurst (Making of Mr. Righteous)
"Take My Butler, Please" / "Horray for Hollywood"  – December 5, 1987: written by Gary Greenfield (Take My Butler, Please), Pat Allee and Ben Hurst (Horray for Hollywood)

References

External links

1987 American television series debuts
1987 American television series endings
1980s American animated television series
1980s American sitcoms
American animated sitcoms
American animated television spin-offs
American children's animated comedy television series
American prequel television series
Animated television series about children
Anime-influenced Western animated television series
Child versions of cartoon characters
English-language television shows
NBC original programming
Television series by Claster Television
Television series by DIC Entertainment
Television series by Saban Entertainment
Television shows based on Archie Comics

The New Archies


Mohamed Lamine Diallo est un médecin et homme politique guinéen.

Il est conseiller depuis le  au sein du Conseil national de la transition dirigé par Dansa Kourouma en tant que représentant des organisations culturelles.

Notes et références

Voir aussi
 Conseil national de la transition

Membre du Conseil national de transition guinéen de 2021

Mohamed Lamine Diallo


es un libro de memorias de Murakami Haruki en el que escribe acerca de su interés y participación en carreras de larga distancia. Murakami empezó a correr a principios de la década de 1980 y desde entonces ha competido en más de veinte maratones y una ultramaratón.

El título del libro fue inspirado en la colección de cuentos cortos de Raymond Carver titulada De qué hablamos cuando hablamos de amor.

Bibliografía

Enlaces externos
Crítica en The New York Times.
Crítica en The New York Sun.
 Crítica en The Los Angeles Times.
Crítica en The Times.
Crítica en The Christian Science Monitor.
Crítica en The Guardian.
Crítica en The Daily Telegraph.
 Crítica en The Daily Telegraph.t

Libros de 2007
Libros de 2010
Libros biográficos
Obras literarias en japonés
Obras literarias de Japón
Autobiografías
Obras de Haruki Murakami
Maratón

De qué hablo cuando hablo de correr


A blood donation occurs when a person voluntarily has blood drawn and used for transfusions and/or made into biopharmaceutical medications by a process called fractionation (separation of whole blood components). Donation may be of whole blood, or of specific components directly (apheresis). Blood banks often participate in the collection process as well as the procedures that follow it.

Today in the developed world, most blood donors are unpaid volunteers who donate blood for a community supply. In some countries, established supplies are limited and donors usually give blood when family or friends need a transfusion (directed donation).  Many donors donate for several reasons, such as a form of charity, general awareness regarding the demand for blood, increased confidence in oneself, helping a personal friend or relative, and social pressure.  Despite the many reasons that people donate, not enough potential donors actively donate.  However, this is reversed during disasters when blood donations increase, often creating an excess supply that will have to be later discarded.  In countries that allow paid donation some people are paid, and in some cases there are incentives other than money such as paid time off from work. People can also have blood drawn for their own future use (autologous donation). Donating is relatively safe, but some donors have bruising where the needle is inserted or may feel faint.

Potential donors are evaluated for anything that might make their blood unsafe to use. The screening includes testing for diseases that can be transmitted by a blood transfusion, including HIV and viral hepatitis. The donor must also answer questions about medical history and take a short physical examination to make sure the donation is not hazardous to their health. How often a donor can donate varies from days to months based on what component they donate and the laws of the country where the donation takes place. For example, in the United States, donors must wait 56 days (eight weeks) between whole-blood donations but only seven days between platelet apheresis donations and twice per seven-day period in plasmapheresis.

The amount of blood drawn and the methods vary. The collection can be done manually or with automated equipment that takes only specific components of the blood. Most of the components of blood used for transfusions have a short shelf life, and maintaining a constant supply is a persistent problem. This has led to some increased interest in autotransfusion, whereby a patient's blood is salvaged during surgery for continuous reinfusion—or alternatively, is self-donated prior to when it will be needed. Generally, the notion of donation does not refer to giving to one's self, though in this context it has become somewhat acceptably idiomatic.

History

Charles Richard Drew (1904–1950) was an American surgeon and medical researcher. He researched in the field of blood transfusions, developing improved techniques for blood storage, and applied his expert knowledge to developing large-scale blood banks early in World War II. This allowed medics to save thousands of lives of the Allied forces. As the most prominent African American in the field, Drew protested against the practice of racial segregation in the donation of blood, as it lacked scientific foundation, and resigned his position with the American Red Cross, which maintained the policy until 1950.

Types of donation

Blood donations are divided into groups based on who will receive the collected blood. An 'allogeneic' (also called 'homologous') donation is when a donor gives blood for storage at a blood bank for transfusion to an unknown recipient. A 'directed' donation is when a person, often a family member, donates blood for transfusion to a specific individual. Directed donations are relatively rare when an established supply exists. A 'replacement donor' donation is a hybrid of the two and is common in developing countries. In this case, a friend or family member of the recipient donates blood to replace the stored blood used in a transfusion, ensuring a consistent supply. When a person has blood stored that will be transfused back to the donor at a later date, usually after surgery, that is called an 'autologous donation'. Blood that is used to make medications can be made from allogeneic donations or from donations exclusively used for manufacturing.

Blood is sometimes collected using similar methods for therapeutic phlebotomy, similar to the ancient practice of bloodletting, which is used to treat conditions such as hereditary hemochromatosis or polycythemia vera. This blood is sometimes treated as a blood donation, but may be immediately discarded if it cannot be used for transfusion or further manufacturing.

The actual process varies according to the laws of the country, and recommendations to donors vary according to the collecting organization. The World Health Organization gives recommendations for blood donation policies, but in developing countries many of these are not followed. For example, the recommended testing requires laboratory facilities, trained staff, and specialized reagents, all of which may not be available or too expensive in developing countries.

An event where donors come to donate allogeneic blood is sometimes called a 'blood drive' or a 'blood donor session'. These can occur at a blood bank, but they are often set up at a location in the community such as a shopping center, workplace, school, or house of worship.

Screening

Donors are typically required to give consent for the process, and meet a certain criteria such as weight and hemoglobin levels, and this requirement means minors cannot donate without permission from a parent or guardian. In some countries, answers are associated with the donor's blood, but not name, to provide anonymity; in others, such as the United States, names are kept to create lists of ineligible donors. If a potential donor does not meet these criteria, they are 'deferred'. This term is used because many donors who are ineligible may be allowed to donate later. Blood banks in the United States may be required to label the blood if it is from a therapeutic donor, so some do not accept donations from donors with any blood disease. Others, such as the Australian Red Cross Blood Service, accept blood from donors with hemochromatosis. It is a genetic disorder that does not affect the safety of the blood.

The donor's race or ethnic background is sometimes important since certain blood types, especially rare ones, are more common in certain ethnic groups. Historically, in the United States donors were segregated or excluded on race, religion, or ethnicity, but this is no longer a standard practice.

Recipient safety

Donors are screened for health risks that could make the donation unsafe for the recipient. Some of these restrictions are controversial, such as restricting donations from men who have sex with men (MSM) because of the risk of transmitting HIV. In 2011, the UK (excluding Northern Ireland) reduced its blanket ban on MSM donors to a narrower restriction which only prevents MSM from donating blood if they have had sex with other men within the past year. A similar change was made in the US in late 2015 by the Food and Drug Administration (FDA). In 2017, the UK and US further reduced their restrictions to three months. In 2023, the FDA announced new policies easing restrictions on gay and bisexual men donating blood. These updated guidelines stipulate that men in monogamous relationships with other men, or who have not recently had sex, can donate. Individuals who report having sex with people who are HIV positive or have had sex with a new partner who has engaged in anal sex are still barred from blood donation. Autologous donors are not always screened for recipient safety problems since the donor is the only person who will receive the blood. Since the donated blood may be given to pregnant women or women of child-bearing age, donors taking teratogenic (birth defect-causing) medications are deferred. These medications include acitretin, etretinate, isotretinoin, finasteride, and dutasteride.

Donors are examined for signs and symptoms of diseases that can be transmitted in a blood transfusion, such as HIV, malaria, and viral hepatitis. Screening may include questions about risk factors for various diseases, such as travel to countries at risk for malaria or variant Creutzfeldt–Jakob disease (vCJD). These questions vary from country to country. For example, while blood centers in Québec and the rest of Canada, Poland, and many other places defer donors who lived in the United Kingdom for risk of vCJD, donors in the United Kingdom are only restricted for vCJD risk if they have had a blood transfusion in the United Kingdom.

Donor safety
The donor is also examined and asked specific questions about their medical history to make sure that donating blood is not hazardous to their health. The donor's hematocrit or hemoglobin level is tested to make sure that the loss of blood will not make them anemic, and this check is the most common reason that a donor is ineligible. Accepted hemoglobin levels for blood donations, by the American Red Cross, is 12.5g/dL (for females) and 13.0g/dL (for males) to 20.0g/dL, anyone with a higher or lower hemoglobin level cannot donate. Pulse, blood pressure, and body temperature are also evaluated. Elderly donors are sometimes also deferred on age alone because of health concerns. In addition to age, weight and height are important factors when considering the eligibility for donors. For example, the American Red Cross requires a donor to be  or more for whole blood and platelet donation and at least  (males) and at least  (females) for power red donations (double red erythrocytapheresis). The safety of donating blood during pregnancy has not been studied thoroughly, and pregnant women are usually deferred until six weeks after the pregnancy.

Blood testing

The donor's blood type must be determined if the blood will be used for transfusions. The collecting agency usually identifies whether the blood is type A, B, AB, or O and the donor's Rh (D) type and will screen for antibodies to less common antigens. More testing, including a crossmatch, is usually done before a transfusion. Type O negative is often cited as the "universal donor" but this only refers to red cell and whole blood transfusions. For plasma and platelet transfusions the system is reversed: AB positive is the universal platelet donor type while both AB positive and AB negative are universal plasma donor types.

Most blood is tested for diseases, including some STDs. The tests used are high-sensitivity screening tests and no actual diagnosis is made. Some of the test results are later found to be false positives using more specific testing. False negatives are rare, but donors are discouraged from using blood donation for the purpose of anonymous STD screening because a false negative could mean a contaminated unit. The blood is usually discarded if these tests are positive, but there are some exceptions, such as autologous donations. The donor is generally notified of the test result.

Donated blood is tested by many methods, but the core tests recommended by the World Health Organization are these four:
 Hepatitis B surface antigen
 Antibody to hepatitis C
 Antibody to HIV, usually subtypes 1 and 2
 Serologic test for syphilis

The WHO reported in 2006 that 56 out of 124 countries surveyed did not use these basic tests on all blood donations.

A variety of other tests for transfusion transmitted infections are often used based on local requirements. Additional testing is expensive, and in some cases the tests are not implemented because of the cost. These additional tests include other infectious diseases such as West Nile fever and babesiosis. Sometimes multiple tests are used for a single disease to cover the limitations of each test. For example, the HIV antibody test will not detect a recently infected donor, so some blood banks use a p24 antigen or HIV nucleic acid test in addition to the basic antibody test to detect infected donors. Cytomegalovirus is a special case in donor testing in that many donors will test positive for it. The virus is not a hazard to a healthy recipient, but it can harm infants and other recipients with weak immune systems.

Obtaining the blood

There are two main methods of obtaining blood from a donor. The most frequent is to simply take the blood from a vein as whole blood. This blood is typically separated into parts, usually red blood cells and plasma, since most recipients need only a specific component for transfusions.

The amount of blood donated in one session – generally called a 'unit' – is defined by the WHO as 450 millilitres. Some countries like Canada follow this standard, but others have set their own rules, and sometimes there is variation even among different agencies within a country. For example, whole blood donations in the United States are in the 460–500 ml range, while those in the EU must be in the 400-500 ml range. Other countries have smaller units – India uses 350 ml, Singapore 350 or 450 ml, and Japan 200 or 400 ml. Historically, donors in the People's Republic of China would donate only 200 ml, though larger 300 and 400 ml donations have become more common, particularly in northern China and for heavier donors. In any case, an additional 5-10 ml of blood may be collected separately for testing.

The other method is to draw blood from the donor, separate it using a centrifuge or a filter, store the desired part, and return the rest to the donor. This process is called apheresis, and it is often done with a machine specifically designed for this purpose. This process is especially common for plasma, platelets, and red blood cells.

For direct transfusions a vein can be used but the blood may be taken from an artery instead. In this case, the blood is not stored, but is pumped directly from the donor into the recipient. This was an early method for blood transfusion and is rarely used in modern practice.  It was phased out during World War II because of problems with logistics, and doctors returning from treating wounded soldiers set up banks for stored blood when they returned to civilian life.

Site preparation and drawing blood

The blood is drawn from a large arm vein close to the skin, usually the median cubital vein on the inside of the elbow. The skin over the blood vessel is cleaned with an antiseptic such as iodine or chlorhexidine to prevent skin bacteria from contaminating the collected blood and also to prevent infections where the needle pierced the donor's skin.

A large needle (16 to 17 gauge) is used to minimize shearing forces that may physically damage red blood cells as they flow through the needle. A tourniquet is sometimes wrapped around the upper arm to increase the pressure of the blood in the arm veins and speed up the process. The donor may also be prompted to hold an object and squeeze it repeatedly to increase the blood flow through the vein.

Whole blood

The most common method is collecting the blood from the donor's vein into a container. The amount of blood drawn varies from 200 millilitres to 550 millilitres depending on the country, but 450 millilitres is typical. The blood is usually stored in a flexible plastic bag that also contains sodium citrate, phosphate, dextrose, and adenine. This combination keeps the blood from clotting and preserves it during storage up to 42 days. Other chemicals are sometimes added during processing.

The plasma from whole blood can be used to make plasma for transfusions or it can also be processed into other medications using a process called fractionation. This was a development of the dried plasma used to treat the wounded during World War II and variants on the process are still used to make a variety of other medications.

Apheresis

Apheresis is a blood donation method where the blood is passed through an apparatus that separates out one particular constituent and returns the remainder to the donor. Usually the component returned is the red blood cells, the portion of the blood that takes the longest to replace. Using this method an individual can donate plasma or platelets much more frequently than they can safely donate whole blood. These can be combined, with a donor giving both plasma and platelets in the same donation.

Platelets can also be separated from whole blood, but they must be pooled from multiple donations. From three to ten units of whole blood are required for a therapeutic dose. Plateletpheresis provides at least one full dose from each donation.

During a platelet donation, the blood is drawn from the patient and the platelets are separated from the other blood components. The remainder of the blood, red blood cells, plasma, and white blood cells are returned to the patient. This process is completed several times for a period of up to two hours to collect a single donation.

Plasmapheresis is frequently used to collect source plasma that is used for manufacturing into medications much like the plasma from whole blood. Plasma collected at the same time as plateletpheresis is sometimes called concurrent plasma.

Apheresis is also used to collect more red blood cells than usual in a single donation (commonly known as "double reds") and to collect white blood cells for transfusion.

Recovery and time between donations

Donors are usually kept at the donation site for 10–15 minutes after donating since most adverse reactions take place during or immediately after the donation. Blood centers typically provide light refreshments, such as orange juice and cookies, or a lunch allowance to help the donor recover. The needle site is covered with a bandage and the donor is directed to keep the bandage on for several hours. In hot climates, donors are advised to avoid dehydration (strenuous exercise and games, alcohol) until a few hours after donation.

Donated plasma is replaced after 2–3 days. Red blood cells are replaced by bone marrow into the circulatory system at a slower rate, on average 36 days in healthy adult males. In one study, the range was 20 to 59 days for recovery. These replacement rates are the basis of how frequently a donor can donate blood.

Plasmapheresis and plateletpheresis donors can donate much more frequently because they do not lose significant amounts of red cells. The exact rate of how often a donor can donate differs from country to country. For example, plasmapheresis donors in the United States are allowed to donate large volumes twice a week and could nominally donate 83 litres (about 22 gallons) in a year, whereas the same donor in Japan may only donate every other week and could only donate about 16 litres (about 4 gallons) in a year.

Iron supplementation decreases the rates of donor deferral due to low hemoglobin, both at the first donation visit and at subsequent donations. Iron-supplemented donors have higher hemoglobin and iron stores. On the other hand, iron supplementation frequently causes diarrhea, constipation and epigastric abdominal discomfort. The long-term effects of iron supplementation without measurement of iron stores are unknown.

Complications
Donors are screened for health problems that would put them at risk for serious complications from donating. First-time donors, teenagers, and women are at a higher risk of a reaction.
One study showed that 2% of donors had an adverse reaction to donation. Most of these reactions are minor. A study of 194,000 donations found only one donor with long-term complications. In the United States, a blood bank is required to report any death that might possibly be linked to a blood donation. An analysis of all reports from October 2008 to September 2009 evaluated six events and found that five of the deaths were clearly unrelated to donation, and in the remaining case they found no evidence that the donation was the cause of death.

Hypovolemic reactions can occur because of a rapid change in blood pressure. Fainting is generally the worst problem encountered.

The process has similar risks to other forms of phlebotomy. Bruising of the arm from the needle insertion is the most common concern. One study found that less than 1% of donors had this problem. A number of less common complications of blood donation are known to occur. These include arterial puncture, delayed bleeding, nerve irritation, nerve injury, tendon injury, thrombophlebitis, and allergic reactions.

Donors sometimes have adverse reactions to the sodium citrate used in apheresis collection procedures to keep the blood from clotting. Since the anticoagulant is returned to the donor along with blood components that are not being collected, it can bind the calcium in the donor's blood and cause hypocalcemia. These reactions tend to cause tingling in the lips, but may cause convulsions, seizure, hypertension, or more serious problems. Donors are sometimes given calcium supplements during the donation to prevent these side effects.

In apheresis procedures, the red blood cells are returned. If this is done manually and the donor receives the blood from a different donor, a transfusion reaction can take place. Manual apheresis is extremely rare in the developed world because of this risk and automated procedures are as safe as whole blood donations.

The final risk to blood donors is from equipment that has not been properly sterilized. In most cases, the equipment that comes in direct contact with blood is discarded after use. Re-used equipment was a significant problem in China in the 1990s, and up to 250,000 blood plasma donors may have been exposed to HIV from shared equipment.

Storage, supply and demand

Storage and blood shelf life

The collected blood is usually stored in a blood bank as separate components, and some of these have short shelf lives. There are no storage methods to keep platelets for extended periods of time, though some were being studied as of 2008. The longest shelf life used for platelets is seven days.

Red blood cells (RBC), the most frequently used component, have a shelf life of 35–42 days at refrigerated temperatures. For (relatively rare) long-term storage applications, this can be extended by freezing the blood with a mixture of glycerol, but this process is expensive and requires an extremely cold freezer for storage. Plasma can be stored frozen for an extended period of time and is typically given an expiration date of one year and maintaining a supply is less of a problem.

Demand for blood
The American Red Cross states that in the United States, someone needs blood every two seconds, and someone needs platelets every thirty seconds.  There is not a consistent demand for each blood type.  One type of blood being in stock does not guarantee that another type is.  Blood banks may have some units in stock but lack others, ultimately causing the patients that need units for specific blood types to have delayed or canceled procedures.  Additionally, every year there is an increase of around 5-7% for transfusions without an increase of donors to balance it as well as a growing population of elderly people that will need more transfusions in the future without a predicted increase in donations to reflect those growing numbers. This was supported in 1998 where blood donations to the Red Cross increased to 8%, totaling 500,000 units but hospitals' need for donations increased by 11%.

Blood donations tend to always be high in demand with numerous accounts repeatedly stating periodic shortages over the decades.  However, this trend is disrupted during national disasters.  The trend demonstrates that people are donating the most during catastrophes when, arguably, donations are not as needed compared to periods without disasters.  From 1988 to 2013, it has been reported that during every national disaster, there was a surplus of donations; a surplus that consisted of over 100 units.  One of the most notable examples of this pattern was the September 11th attacks. A study observed that compared to the four weeks before September 11, there was an estimated increase of 18,700 donations from first-time donors for the first week after the attack: 4,000 was the average of donations from first-time donors before the attack which increased to about 22,700 donations; while repeat donors increased their donations by 10,000 per week:  initially, donations were estimated to be around 16,400 which increased to 26,400 donations after September 11.  Therefore, in the first week after the attack on 9/11, there was an overall estimated 28,700 increase in donations compared to the average weekly donations made four weeks prior to the attack.  Increases in donations were observed in all blood donation centers, beginning on the day of the attack. While blood donations were above average after the first few weeks following 9/11, the number of donations fell from an estimated 49,000 donations in the first week to 26,000–28,000 donations between the second and fourth weeks after 9/11. Despite the substantial increase of donors, the rate that first-time donors would become repeat donors were the same before and after the attack.

The limited storage time means that it is difficult to have a stockpile of blood to prepare for a disaster. The subject was discussed at length after the September 11 attacks in the United States, and the consensus was that collecting during a disaster was impractical and that efforts should be focused on maintaining an adequate supply at all times. Blood centers in the U.S. often have difficulty maintaining even a three-day supply for routine transfusion demands.

Donation levels
The World Health Organization (WHO) recognizes World Blood Donor Day on 14 June each year to promote blood donation. This is the birthday of Karl Landsteiner, the scientist who discovered the ABO blood group system. The theme of the 2012 World Blood Donor Day campaign, "Every blood donor is a hero" focuses on the idea that everyone can become a hero by giving blood. Based on data reported by 180 countries between 2011 and 2013, the WHO estimated that approximately 112.5 million units of blood were being collected annually.

In the United States it is estimated that 111 million citizens are eligible blood donors, or 37% of the population. However less than 10% of the 37% eligible blood donors donate annually. In the UK the NHS reports blood donation levels at "only 4%" while in Canada the rate is 3.5%.

Donator's incentive and deterrence
Multiple studies have shown that the main reason people donate is due to selflessness, charity, general awareness regarding the demand for blood, increased confidence in oneself, helping a personal friend/relative, and social pressure.  On the other hand, lack of blood donations can occur due to fear, lack of faith in the medical professionals, inconvenience, and the lack of consideration for donating.  Pathologist Leo McCarthy states that blood shortages routinely occur between July 4 and Labor day and between Christmas and New Year.

Donor health benefits
In patients prone to iron overload, blood donation prevents the accumulation of toxic quantities. Donating blood may reduce the risk of heart disease for men, but the link has not been firmly established and may be from selection bias because donors are screened for health problems.

Research published in 2012 demonstrated that in patients with metabolic syndrome, repeated blood donation is effective in reducing blood pressure, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and heart rate.

A study published in JAMA Network Open tracked PFAS levels in a clinical trial and showed that regular blood or plasma donations resulted in a significant reduction in PFAS levels for the participants.

Donor compensation

The World Health Organization set a goal in 1997 for all blood donations to come from unpaid volunteer donors, but as of 2006, only 49 of 124 countries surveyed had established this as a standard. Some countries, such as Tanzania, have made great strides in moving towards this standard, with 20 percent of donors in 2005 being unpaid volunteers and 80 percent in 2007, but 68 of 124 countries surveyed by WHO had made little or no progress. Most plasmapheresis donors in the United States are still paid for their donations. Donors are now paid between $25 and $50 per donation. In some countries, for example Brazil and the United Kingdom, it is illegal to receive any compensation, monetary or otherwise, for the donation of blood or other human tissues.

Regular donors are often given some sort of non-monetary recognition. Time off from work is a common benefit. For example, in Italy, blood donors receive the donation day as a paid holiday from work. Blood centers will also sometimes add incentives such as assurances that donors would have priority during shortages, free T-shirts, first aid kits, windshield scrapers, pens, and similar trinkets. There are also incentives for the people who recruit potential donors, such as prize drawings for donors and rewards for organizers of successful drives. Recognition of dedicated donors is common. For example, the Singapore Red Cross Society presents awards for voluntary donors who have made a certain number of donations under the Blood Donor Recruitment Programme starting with a "bronze award" for 25 donations. In Ireland the Irish Blood Transfusion Service awards a silver pin or pendant for 10 donations, a gold pin or pendant for 20 donations, a gold lapel pin for 50 donations while those reaching 100 donations attend a dinner ceremony where they are presented with a small porcelain statue depicting the logo of the IBTS (a pelican). The government of Malaysia also offers free outpatient and hospitalization benefits for blood donors, for example, 4 months of free outpatient treatment and hospitalization benefits after every donation. In Poland, after donating a specific amount of blood (18 litres for men and 15 for women), a person is gifted with the title of "Distinguished Honorary Blood Donor" as well as a medal. In addition, a popular privilege in larger Polish cities is the right to free use of public transport, but the conditions for obtaining a privilege may vary depending on the city. During the COVID-19 pandemic, many US blood centers advertised free COVID-19 antibody testing as an incentive to donate, however these antibody tests were also useful for blood centers in determining which donors could be flagged for convalescent plasma donations.

Most allogeneic blood donors donate as an act of charity and do not expect to receive any direct benefit from the donation. The sociologist Richard Titmuss, in his 1970 book The Gift Relationship: From Human Blood to Social Policy, compared the merits of the commercial and non-commercial blood donation systems of the US and the UK, coming down in favor of the latter. The book became a bestseller in the US, resulting in legislation to regulate the private market in blood. The book is still referenced in modern debates about turning blood into a commodity. The book was republished in 1997 and the same ideas and principles are applied to analogous donation programs, such as organ donation and sperm donation.

See also
 Blood bank#History (history of blood donation)
 Blood donation restrictions on men who have sex with men
 Blood substitute
 James Harrison (blood donor)
 List of blood donation agencies
 World Blood Donor Day
 Xenotransfusion

References

Further reading

 Deferred Donors: Anemia & Blood Donation
 British guidelines for transfusion medicine

Blood donation
Hematology
Transfusion medicine

Blood donation


Hirokazu Otsubo (født 7. december 1979) er en tidligere japansk fodboldspiller.

Han har spillet for flere forskellige klubber i sin karriere, herunder Ehime FC.

Eksterne henvisninger

Fodboldspillere fra Japan

Hirokazu Otsubo


Erdoğan Olcayto, (d. 1931  ö. 03 Ekim 2012 ) Türk gazetecidir.

Saint Joseph Lisesi'ni bitirdikten sonra İstanbul Üniversitesi Hukuk Fakültesi'ne girdi. Mesleğe 1956 yılında Anadolu Ajansı'nda muhabir olarak başladı. Bu görevinden sonra Almanya'ya gitti. Almanya'da çalışan Türk işçileri için gazete çıkarmaya yönelik bir proje hazırladı ve Alman Basın Yayın Genel Müdürlüğü tarafından 1963 yılında hazırladığı projeyi hayata geçirmekle görevlendirdi. Yedi yıl boyunca bu gazetede yazı işleri müdürlüğü yaptı. 1965-71 döneminde Anadolu Ajansı Almanya temsilciliği yaptı. Anadolu Ajansı tarafından 1972 yılında İstanbul'a çağrıldı ve AA İstanbul Bölge Müdürü olarak görevlendirildi. Bu görevi bir yıl sürdürdükten sonra 1974 yılında tekrar Almanaya'ya döndü. 1979'a kadar Tercüman Gazetesi'nin Almanya temsilciliğini yaptı. 1979'da Almanya'daki Türk işçileri için haftalık Anadolu Gazetesi'ni çıkarmaya başladı. Anadolu Gazetesi 1982'ye kadar devam etti. 1983-87 yılları arasında Hürriyet Gazetesi'nin Bonn temsilciliğini yaptı. 1987'de aylık Almanca ekonomi gazetesi Türkei-Kurier'i çıkarmaya başladı. 1992 yılında bu gazeteyi İstanbul'a taşıdı.

Erdoğan Olcayto aynı zamanda Türkiye Gazeteciler Cemiyeti "Burhan Felek Basın Hizmet Ödülü" ve İstanbul Gazeteciler Derneği'nin "Altın Hizmet Ödülü"ne sahip bulunuyor. 2009 yılı ortalarında EuroTurk Group'a devredilen Türkei-Kurier Gazetesi daha sonra ise yayın hayatına veda etti.

Kaynakça

1931 doğumlular
Saint Joseph Fransız Lisesinde öğrenim görenler
İstanbul Üniversitesi Hukuk Fakültesinde öğrenim görenler
20. yüzyıl Türk gazetecileri
21. yüzyıl Türk gazetecileri
Burhan Felek Basın Hizmet Ödülü sahipleri

Erdoğan Olcayto


Banari (sardisk: Bànari) er en by og en kommune (comune) i provinsen Sassari i regionen Sardinien i Italien. Byen ligger i 419 meters højde og har 580 indbyggere (2016). Kommunen har et areal på 21,25 km² og grænser til kommunerne Bessude, Florinas, Ittiri og Siligo.

Referencer

Henvisninger

Kommuner i provinsen Sassari

Banari


Le paso Hua Hum () est un passage routier frontalier situé dans les Andes, entre le Chili et l'Argentine. Il tire son nom du río Hua-hum qui coule de l'Argentine au Chili sur le site du passage frontalier. Même s'il ne traverse pas la ligne continentale de partage des eaux, il permet de franchir les plus hauts sommets de la cordillère.

Géographie

Le paso Hua Hum est l'un des passages les plus bas du sud des Andes à 685 mètres d'altitude, ce qui signifie que contrairement aux autres cols Chili-Argentine à proximité, il n'est jamais fermé à cause de la de neige et est donc ouvert toute l'année. Ce passage frontalier est principalement à usage touristique, car la route chilienne CH-203 est interrompue par le lac Pirihueico, de forme allongée et sinueuse du nord-ouest au sud-est, qu'il est ensuite possible de franchir en ferry à partir de . Le trajet en ferry dure environ 1 heure 30.

C'est le passage principal de la région chilienne de Los Ríos à la province de Neuquén en Argentine. Les principales villes des deux côtés de la frontière sont Panguipulli au Chili et San Martín de los Andes (à 45 km en Argentine).

Notes et références

Cordillère des Andes
Province de Valdivia
Province de Neuquén

Paso Hua Hum


Francisco de Borbón (Madrid, 16 de noviembre de 1943),  duque de Sevilla, grande de España, es un noble y empresario español.

Familia
Hijo de Francisco de Paula Enrique María Luis de Borbón y Borbón y de su mujer Enriqueta Escasany y Miguel, nieto paterno de la IV duquesa de Sevilla, grande de España, Enriqueta Isabel Josefina Alfonsa Marta María Elena Luisa Carlota de Borbón y Parade y nieto materno de la II marquesa de Pobla de Claramunt, Enriqueta de Miguel y Mas.

Biografía
Licenciado en Económicas, es administrador de empresas y banquero. Inició su trayectoria profesional en 1973 como director del banco de negocios londinense Hill Samuel and Co. Limited, qué dirigió hace treinta años, convirtiéndose luego y desempeñando posteriormente los cargos de presidente y director general del Miami National Bank y presidente del Cannon Group Iberoamérica.

Es primo cuarto del rey emérito Juan Carlos I y hermano de Alfonso Carlos de Borbón y Escasany, con quien comparte puestos ejecutivos y vocalías en los consejos de administración de las empresas familiares. Además, es consejero delegado de Ahorro Familiar, presidente de la Sociedad Internacional de Equipos Clínicos, SA o Sociedad Internacional de Equipos Médicos, con 270 000 € de capital social, que participa en la American Liberty de Equipos Clínicos, en los Estados Unidos, y de Vapor, SA, dedicada al comercio de maquinaria y equipos industriales, y administrador único de Compañía Médica y Educacional de Sevilla, SA, dedicada a la venta de productos sanitarios, con 962 000 € de capital social, y de Kingnoi, SA, de gestión y administración inmobiliaria, y principal accionista de Polaris Inversiones Inmobiliarias y Financieras, SL.

Matrimonios y descendencia
Francisco se casó en Baden-Baden el 7 de julio de 1973 con la condesa Beatrice Wilhelmine Paula von Hardenberg-Fürstenberg (Donaueschingen, 28 de junio de 1947 - Marbella, 14 de marzo de 2020), hija del conde Günther Eberhard Kurt Wilhelm von Hardenberg (Schwedt an der Oder, 14 de febrero de 1918 - Baden-Baden, 19 de enero de 1985) y de su esposa, (Donaueschingen, 27 de febrero de 1943) la princesa Maria Josepha Egona Sofia Wilhelmine Joachima Maximiliane Friederike zu Fürstenberg (Werenwag, 23 de abril de 1922 - Baden-Baden, 7 de julio de 2008). Antes de divorciarse en Madrid el 30 de junio de 1989, tuvieron dos hijas y un hijo:
 Olivia Enriqueta María Josefa de Borbón y von Hardenberg-Fürstenberg (Londres, 6 de abril de 1974). Empresaria, creó la firma de joyas Aristocrazy.  Está casada con Julián Porras-Figueroa y Toledano y son padres de dos niños, Flavia y Fernando.
 Cristina Elena de Borbón y von Hardenberg-Fürstenberg (Madrid, 2 de septiembre de 1975 - Madrid, 13 de febrero de 2020), traductora del IECSA de Buenos Aires y del ASAP SL de Madrid, ayudaba a organizar eventos deportivos, estudió Relaciones Internacionales en el College for International Studies (CIS) de Madrid, y tenía una compañía de cáterin. Fallecida en el Hospital Puerta del Hierro tras un accidente el 13 de febrero de 2020.
 Francisco de Paula Joaquín de Borbón y von Hardenberg-Fürstenberg (Madrid, 21 de enero de 1979), conde de Hardenberg-Fürstenberg, trabajó en ASAP SL tras estudiar Gestión Deportiva en la Barry University y vive en Madrid. El día 24 de agosto de 2021 anunció oficialmente que se casará con la madre de su hijo Francisco Máximo que nació el 3 de noviembre de 2017, la empresaria austriaca, Sophie Karoly en Sevilla el 9 de octubre de 2021.  Sophie es directora general de Avantgarde Properties, con sede en Viena (Austria), trabaja entre Viena, Madrid y Marbella.

Volvió a contraer matrimonio en Viena el 19 de octubre de 1991 con Isabelle Eugénie Karanitsch (Viena, 23 de noviembre de 1959), hija de Franz M. Karanitsch y de Tatjana Cimlov Karacevcev. Divorciados en Madrid el 17 de junio de 1993. Sin descendencia.

Se casó por tercera vez en Marbella el 2 de septiembre de 2000 con María de los Ángeles de Vargas-Zúñiga y Juanes (19 de noviembre de 1954), hija de Manuel de Vargas-Zúñiga y la Calzada y de María de los Ángeles de Juanes y Lago y nieta paterna del  conde de la Oliva de Plasencia. Sin descendencia.

Distinciones honoríficas
 Consejero Magistral (Presidente) del Cuerpo de la Nobleza del Principado de Asturias, por acuerdo de la Junta de Gobierno de 15 de abril de 2010.
Hermano Honorario de la Real Cofradía de El Prendimiento de Nuestro Señor Jesucristo de Hellín (Albacete), por acuerdo de la Junta de Gobierno de 31 de mayo de 2015.
Comendador de la Real Orden del Mérito Civil
Gran Maestre Emérito de la Orden Militar y Hospitalaria de San Lázaro de Jerusalén
Presidente de Honor de la Asociación Santos Ángeles Custodios de España, Amigos del Cuerpo Nacional de Policía

Ancestros

Títulos

Referencias

Nobles de la Comunidad de Madrid
Casa de Borbón en España
Duques de Sevilla
Grandeza de España
Economistas de España del siglo XXI
Empresarios de España
Banqueros de España
Grandes maestres de la Orden de San Lázaro de Jerusalén
Nacidos en Madrid

Francisco de Paula de Borbón y Escasany


J. R. "Bob" Dobbs é a figura principal da religião paródia  Igreja do SubGenius. Sua imagem é derivada de uma coleção de clipart distribuída pela Bell Telephone Company of West Texas em 1946.

De acordo com o dogma SubGenius, "Bob" era um vendedor de equipamentos de perfuração que, em 1953, teve uma visão do deus JHVH-1 em um aparelho de televisão que havia construído.  A visão o inspirou a escrever as "PreEscrituras" (conforme descritas no Livro do SubGenius) e fundar a Igreja. A teologia afirma que "Bob" é o maior vendedor que já existiu e enganou a morte várias vezes. Ele também é reverenciado por suas grandes loucuras e acredita-se ser o salvador do "Slack". Ele foi assassinado em São Francisco em 1984, embora a Igreja afirme que ele voltou dos mortos várias vezes desde então.

As aspas no nome de "Bob" sempre são incluídas na grafia de seu nome, segundo a Igreja.

História pessoal
De acordo com Apocalipse X; O "Bob" Apócrifo, "Bob" nasceu em Dallas, Texas, filho de Xinucha-Chi-Xan M. Dobbs (um farmacêutico) e Jane McBride Dobbs.  Em tenra idade, ele possuía o talento de ganhar grandes quantias de dinheiro jogando no mercado de ações pelo telefone. Ele se casou com sua esposa Connie em Las Vegas em 1955 e trabalhou como modelo de fotógrafo enquanto inventava e patenteava itens de mordaça inovadores. Em 1957, ele trabalhava nos fins de semana fazendo pregações cristãs evangélicas "estritamente por dinheiro".

O conto de Robert Anton Wilson "The Horror on Howth Hill" envolve uma conversa entre Dobbs e o cientista louco De Selby.

Connie Dobbs
Constance "Connie" Marsh Dobbs, a esposa de "Bob", tornou-se quase tão lendária nos círculos SubGenius quanto "Bob". Embora "Bob" tenha sido casado com outras mulheres, espíritos, divindades e objetos inanimados, Connie é descrita no documentário SubGenius Arise! como "sua primeira e ainda sua primeira esposa". Connie, uma atriz e modelo que formou o Home for Slackless Children,  é a patrona das mulheres SubGenius e é vista como uma visão de verdadeira libertação para as mulheres. Ela se recusa a se submeter a qualquer pessoa (especialmente "Bob") e é tão livre e promíscua quanto o marido, embora tenha uma cabeça mais equilibrada quando se trata de questões domésticas.

Dobbstown
De acordo com a tradição da Igreja, "Bob" viajou para Sarauaque, na Malásia, e fundou seu quartel-general, um enclave secreto lá, chamado Dobbstown, onde costuma ficar.

Imagens de "Bob"

A imagem "Bob" apareceu pela primeira vez na publicação original da SubGenius, SubGenius Pamphlet #1 (aka "O mundo acaba amanhã e você pode morrer") (1979).  Desde sua aparição inicial, seu rosto apareceu em vários lugares ao redor do mundo, e fez aparições em tudo, desde graffiti em viadutos de rodovias e como parte do conjunto de caracteres gráficos do sistema operacional Atari ST, até álbuns musicais de muitos bandas underground (e várias bandas populares de rock mainstream, variando de Devo a Sublime) e o filme ocasional (The Wizard of Speed and Time), programa de TV (Pee-wee's Playhouse) e desenho animado (SpongeBob SquarePants). Há também dois quadrinhos alemães com "Bob" ("Future Subjunkies" e "Space Bastards", ambos de Gerhard Seyfried e Ziska Riemann). A Igreja do SubGenius mantém a marca registrada e os direitos autorais da imagem  "Bob", embora tenha tentado evitar ações legais, a menos que seja absolutamente necessário. A imagem  "Bob" é comumente vista no grupo de notícias Usenet alt.binaries.slack, onde ele aparece regularmente em imagens de muitos artistas. A etiqueta apropriada no grupo de notícias determina que o crédito seja dado onde é devido, e o reconhecimento da propriedade da imagem de "Bob" pela Igreja é aceito pelos  regulares do grupo de notícias.

J.R. "Bob" Dobbs serviu de inspiração para o personagem do Professor Utônio no desenho animado As Meninas Superpoderosas.  O personagem da DC Comics, Doc Magnus, também tem uma forte semelhança visual com "Bob".

Sacred Ikon
Por volta de 2002, a Igreja adotou um novo símbolo chamado "Sacred Ikon", que é uma cruz estilizada composta por três barras e um cachimbo, colocados em um padrão que combina com os olhos, nariz, boca e cachimbo de "Bob".

Enquete da Time
Em seu primeiro tópico em 1° de janeiro de 2000, uma revista Time baseada em votações na Internet nomeou J.R. "Bob" Dobbs a "Mentira Ou Fraude" número 1 do século XX.

Ligações externas

Estadunidenses fictícios

J. R. "Bob" Dobbs


Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing. In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.

There are about 36 different types of amyloidosis, each due to a specific protein misfolding. Within these 36 proteins, 19 are grouped into localized forms, 14 are grouped as systemic forms, and 3 proteins can identify as either. These proteins can become irregular due to genetic effects, as well as through acquired environmental factors. The four most common types of systemic amyloidosis are light chain (AL), inflammation (AA), dialysis-related (Aβ2M), and hereditary and old age (ATTR and Wild-type transthyretin amyloid).

Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. Due to the variable presentation, a diagnosis can often take some time to reach.

Treatment is geared towards decreasing the amount of the involved protein. This may sometimes be achieved by determining and treating the underlying cause. AL amyloidosis occurs in about 3–13 per million people per year and AA amyloidosis in about 2 per million people per year. The usual age of onset of these two types is 55 to 60 years old. Without treatment, life expectancy is between six months and four years. In the developed world about 1 per 1,000 people die annually from systemic amyloidosis. Amyloidosis has been described since at least 1639.

Signs and symptoms

The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved.

Kidneys
Amyloid deposition in the kidney often involve the glomerular capillaries and mesangial regions, affecting the organ's ability to filter and excrete waste and retain plasma protein. This can lead to high levels of protein in the urine (proteinuria) and nephrotic syndrome. Several types of amyloidosis, including the AL and AA types, are associated with nephrotic syndrome. Approximately 20% and 40–60% of people with AL and AA amyloidosis respectively progress to end-stage kidney disease requiring dialysis.

Heart

Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction. On echocardiography, the heart shows a restrictive filling pattern, with normal to mildly reduced systolic function. AA amyloidosis usually spares the heart. Cardiac amyloidosis can present with symptoms of heart failure including shortness of breath, fatigue, and edema. As cardiac amyloidosis progresses, the amyloid deposition can affect the heart's ability to pump and fill blood as well as its ability to maintain normal rhythm, which leads to worsening heart function and decline in people's quality of life.

Nervous system
People with amyloidosis may have central nervous system involvement, along with peripheral involvement which causes sensory and autonomic neuropathies. Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety. Amyloidosis of the central nervous system can have more severe and systemic presentations that may include life-threatening arrhythmias, cardiac failure, malnutrition, infection, or death.

Neuropathic presentation can depend on the etiology of amyloidosis. People with amyloidosis may experience dysfunction in various organ systems depending on the location and extent of nervous system involvement. For example, peripheral neuropathy can cause erectile dysfunction, incontinence and constipation, pupillary dysfunction, and sensory loss depending on the distribution of amyloidosis along different peripheral nerves.

Gastrointestinal and accessory organs
Accumulation of amyloid proteins in the gastrointestinal system may be caused by a wide range of amyloid disorders and have different presentations depending on the degree of organ involvement. Potential symptoms include weight loss, diarrhea, abdominal pain, heartburn (gastrointestinal reflux), and GI bleeding. Amyloidosis may also affect accessory digestive organs including the liver, and may present with jaundice, fatty stool, anorexia, fluid buildup in the abdomen, and spleen enlargement.

Accumulation of amyloid proteins in the liver can lead to elevations in serum aminotransferases and alkaline phosphatase, two biomarkers of liver injury, which is seen in about one third of people. Liver enlargement is common. In contrast, spleen enlargement is rare, occurring in 5% of people. Splenic dysfunction, leading to the presence of Howell-Jolly bodies on blood smear, occurs in 24% of people with amyloidosis. Malabsorption is seen in 8.5% of AL amyloidosis and 2.4% of AA amyloidosis. One suggested mechanism for the observed malabsorption is that amyloid deposits in the tips of intestinal villi (fingerlike projections that increase the intestinal area available for absorption of food),  begin to erode the functionality of the villi, presenting a sprue-like picture.

Glands
Both the thyroid and adrenal glands can be infiltrated. It is estimated that 10–20% of people with amyloidosis have hypothyroidism. Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to autonomic neuropathy and heart failure.

"Amyloid deposits occur in the pancreas of people who also have diabetes mellitus, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or 'amylin.' This is stored with insulin in secretory granules in [beta] cells and is co secreted with insulin." (Rang and Dale's Pharmacology, 2015.)

Musculoskeletal system
Amyloid proteins deposit most commonly inside the knee, followed by hands, wrists, elbow, hip, and ankle, causing joint pain. In males with advanced age (>80 years), there is significant risk of wild-type transthyretin amyloid deposition in synovial tissue of knee joint, but predominantly in old age deposition of wild type transthyretin is seen in cardiac ventricles. ATTR deposits have been found in ligamentum flavum of patients that underwent surgery for lumbar spinal stenosis.

In beta 2-microglobulin amyloidosis, males have high risk of getting carpal tunnel syndrome. Aβ2MG amyloidosis (Hemodialysis associated amyloidosis) tends to deposit in synovial tissue, causing chronic inflammation of the synovial tissue in knee, hip, shoulder and interphalangeal joints. Amyloid light chains deposition in shoulder joint causes enlarged shoulders, also known as "shoulder pad sign". Amyloid light chain depositions can also cause bilateral symmetric polyarthritis.

The deposition of amyloid proteins in the bone marrow without causing plasma cell dyscrasias is called amyloidoma. It is commonly found in cervical, lumbar, and sacral vertebrae. Those affected may be presented with bone pain due to bone lysis, lumbar paraparesis, and a variety of neurological symptoms. Vertebral fractures are also common.

Eyes
A rare development is amyloid purpura, a susceptibility to bleeding with bruising around the eyes, termed "raccoon-eyes". Amyloid purpura is caused by amyloid deposition in the blood vessels and reduced activity of thrombin and factor X, two clotting proteins that lose their function after binding with amyloid.

Oral cavity
Amyloid deposits in tissue can cause enlargement of structures. Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste. Tongue enlargement does not occur in ATTR or AA amyloidosis. Deposition of amyloid in the throat can cause hoarseness.

Pathogenesis

Amyloidoses can be considered protein misfolding diseases. The vast majority of proteins that have been found to form amyloid deposits are secreted proteins, so the misfolding and formation of amyloid occurs outside cells, in the extracellular space. Of the 37 proteins so far identified as being vulnerable to amyloid formation, only four are cytosolic. Most amyloid-forming proteins are relatively small, but otherwise there is currently no evidence of structural or functional similarities among proteins known to form disease-associated amyloids.  One third of amyloid disease is hereditary, in which case there is normally an early age of onset. Half of amyloid-related diseases are sporadic and have a late age of onset – in these cases, the protein aggregation may be associated with aging-related decline in protein regulation. Some medical treatments are associated with amyloid disease, but this is rare.

Amyloid-forming proteins aggregate into distinctive fibrillar forms with a beta-sheet structure. The beta-sheet form of amyloid is proteolysis-resistant, meaning it can not be degraded or broken down. As a result, amyloid deposits into the body's extracellular space. The process of forming amyloid fibrils is thought to have intermediate oligomeric forms. Both the oligomers and amyloid fibrils can be toxic to cells and can interfere with proper organ function. The relative significance of different aggregation species may depend on the protein involved and the organ system affected.

Diagnosis
Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. Also, thioflavin T stain may be used. A number of imaging techniques such as a PYP scan, DPD scan or SAP scan are also in use.

A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a "fat pad biopsy", due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people.

In the amyloid deposition of the joints, there will be a decreased signal in both T1 and T2 weighted MRI images. In amyloidoma, there will be low T1 signal with gadolinium injection and low T2 signal.

The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on protein electrophoresis or light chain determination); binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry); or extraction of the protein and identification of its individual amino acids. Immunohistochemistry can identify AA amyloidosis the majority of the time, but can miss many cases of AL amyloidosis. Laser microdissection with mass spectrometry is the most reliable method of identifying the different forms of amyloidosis.

AL was previously considered the most common form of amyloidosis, and a diagnosis often begins with a search for plasma cell dyscrasia, memory B cells producing aberrant immunoglobulins or portions of immunoglobulins. Immunofixation electrophoresis of urine or serum is positive in 90% of people with AL amyloidosis. Immunofixation electrophoresis is more sensitive than regular electrophoresis but may not be available in all centers. Alternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cells can be sought in people with a high clinical suspicion for AL amyloidosis but negative electrophoresis.

ATTR is now considered to be the most common form of amyloidosis. It may be either age related in wild-type ATTR (ATTRv) or familial transthyretin-associated amyloidosis, is suspected in people with family history of idiopathic neuropathies or heart failure who lack evidence of plasma cell dyscrasias. ATTR can be identified using isoelectric focusing which separates mutated forms of transthyretin. Findings can be corroborated by genetic testing to look for specific known mutations in transthyretin that predispose to amyloidosis.

AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases. AA can be identified by immunohistochemistry staining.

Classification
Historical classification systems were based on clinical factors. Until the early 1970s, the idea of a single amyloid substance predominated. Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. Most classification systems included primary (i.e., idiopathic) amyloidosis, in which no associated clinical condition was identified, and secondary amyloidosis (i.e., secondary to chronic inflammatory conditions). Some classification systems included myeloma-associated, familial, and localized amyloidosis.

The modern era of amyloidosis classification began in the late 1960s with the development of methods to make amyloid fibrils soluble. These methods permitted scientists to study the chemical properties of amyloids. Descriptive terms such as primary amyloidosis, secondary amyloidosis, and others (e.g., senile amyloidosis), which are not based on cause, provide little useful information and are no longer recommended.

The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the majority of deposits, prefixed with the letter A. For example, amyloidosis caused by transthyretin is termed "ATTR". Deposition patterns vary between people but are almost always composed of just one amyloidogenic protein. Deposition can be systemic (affecting many different organ systems) or organ-specific. Many amyloidoses are inherited, due to mutations in the precursor protein.

Other forms are due to different diseases causing overabundant or abnormal protein production – such as with overproduction of immunoglobulin light chains (termed AL amyloidosis), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloidosis).

About 60 amyloid proteins have been identified so far. Of those, at least 36 have been associated with a human disease.

All amyloid fibril proteins start with the letter "A" followed by the protein suffix (and any applicable specification). See below for a list of amyloid fibril proteins which have been found in humans:

Alternative
An older clinical method of classification refers to amyloidoses as systemic or localised:
 Systemic amyloidoses affect more than one body organ or system. Examples are AL, AA and Aβ2m.
 Localised amyloidoses affect only one body organ or tissue type. Examples are Aβ, IAPP, Atrial natriuretic factor (in isolated atrial amyloidosis), and Calcitonin (in medullary carcinoma of the thyroid)

Another classification is primary or secondary.
 Primary amyloidoses arise from a disease with disordered immune cell function, such as multiple myeloma or other immunocyte dyscrasias.
 Secondary (reactive) amyloidoses occur as a complication of some other chronic inflammatory or tissue-destroying disease. Examples are reactive systemic amyloidosis and secondary cutaneous amyloidosis.

Additionally, based on the tissues in which it is deposited, it is divided into mesenchymal (organs derived from mesoderm) or parenchymal (organs derived from ectoderm or endoderm).

Treatment
Treatment depends on the type of amyloidosis that is present. Treatment with high dose melphalan, a chemotherapy agent, followed by stem cell transplantation has shown promise in early studies and is recommended for stage I and II AL amyloidosis. However, only 20–25% of people are eligible for stem cell transplant. Chemotherapy treatment including cyclophosphamide-bortezomib-dexamethasone is currently the recommended treatment option for people with AL Amyloidosis not eligible for transplant.

In AA, symptoms may improve if the underlying condition is treated. In people who have inflammation caused by AA amyloidosis, tumour necrosis factor (TNF)-alpha inhibitors such as infliximab and etanercept are used for an average duration of 20 months. If TNF-alpha inhibitors are not effective, Interleukin-1 inhibitors (e.g., anakinra, canakinumab, rilonacept) and interleukin-6 inhibitors (e.g., tocilizumab) may be considered.

Management of ATTR amyloidosis will depend on its classification as wild type or variant. Both may be treated with tafamidis, a low toxicity oral agent that prevents destabilization of correctly folded protein. Studies showed tafamidis reduced mortality and hospitalization due to heart failure. Previously, for variant ATTR amyloidosis, liver transplant was the only effective treatment. New therapies include diflunisal, inotersen, and patisiran.

Diflunisal binds to misfolded mutant TTR protein to prevent its buildup, like how tafamidis works. Low-certainty evidence indicates that it mitigates worsening of peripheral neuropathy and disability from disease progression.

Inotersen blocks gene expression of both wild-type and mutant TTR, reducing amyloid precursor. Moderate-certainty evidence suggests that it mitigates worsening of peripheral neuropathy. Long-term efficacy and safety of inotersen use in people with mutant TTR-related amyloidosis is still be evaluated in a phase-III clinical trial as of 2021. Both diflunisal and inotersen may also mitigate declines in quality-of-life, though the evidence for this effect is unclear. For people with cardiac ATTR the effect of inotersen use is inconclusive and requires further investigation. In 2018, inotersen was approved by the European Medicines Agency to treat polyneuropathy in adults with hereditary transthyretin amyloidosis. It has since been approved for use in Canada, the European Union and in the USA.

Patisiran functions similarly to inotersen. Moderate-certainty evidence suggests that patisiran mitigates worsening of peripheral neuropathy and disability from disease progression. Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate of adverse events versus placebo. There is no evidence of an effect on mortality rate. A review of early data from use of patisiran in people with variant cardiac ATTR suggests that it may reduce mortality and hospitalization, however this is still being investigated and requires further investigation. In 2018, patisiran was not recommended by NICE in the UK for hereditary transthyretin-related amyloidosis. As of July 2019 further review however is occurring. It was approved for this use in the United States, however.

The roles of inotersen and patisiran in cardiac ATTR amyloidosis are still being investigated.

In 2021, in a clinical trial using the CRISPR gene-editing technique, several participants had an "80% to 96% drop in TTR levels, on par or better than the average of 81%" who were given patisiran.

Vutrisiran was approved by the U.S. Food and Drug Administration (FDA) in June 2022, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

Support groups
People affected by amyloidosis are supported by organizations, including the Amyloidosis Research Consortium, Amyloidosis Foundation, Amyloidosis Support Groups, and Australian Amyloidosis Network.

Prognosis
Prognosis varies with the type of amyloidosis and the affected organ system. Prognosis for untreated AL cardiac amyloidosis is poor, with a median survival of six months. More specifically, AL amyloidosis can be classified as stage I, II or III based on cardiac biomarkers like Nt-proBNP and cardiac troponin.  Survival diminishes with increasing stage, but recent advancements in treatments have improved median survival rates for stages I, II, and III, to 91.2, 60, and 7 months respectively.

Outcomes in a person with AA amyloidosis depend on the underlying disease, organ(s) affected, and correlate with the concentration of serum amyloid A protein.

People with ATTR, mutant ATTR and wild-type ATTR have a better prognosis when compared to people with AL and may survive for over a decade. Survival time is not associated with gender or age, however, some measures of reduced heart function are associated with a shorter survival time.

Senile systemic amyloidosis was determined to be the primary cause of death for 70% of people over 110 who have been autopsied.

Epidemiology
Amyloidosis has a combined estimated prevalence of 30 per 100,000 persons with the three most common forms being AL, ATTR, and AA. The median age at diagnosis is 64.

AL has the highest incidence at approximately 12 cases per million persons per year and an estimated prevalence of 30,000 to 45,000 cases in the US and European Union.

AA amyloidoses is the most common form in developing countries and can complicate longstanding infections with tuberculosis, osteomyelitis, and bronchiectasis. AA amyloidosis is caused by an increase in extracellular deposition of serum amyloid A (SAA) protein. SAA protein levels can rise in both direct and indirect manners, through infection, inflammation, and malignancies. The most common causes of AA amyloidosis in the West are rheumatoid arthritis, inflammatory bowel disease, psoriasis, and familial Mediterranean fever.

People undergoing long-term hemodialysis (14–15 years) can develop amyloidosis from accumulation of light chains of the HLA 1 complex which is normally filtered out by the kidneys.

Wild-type transthyretin (ATTR) amyloidosis is found in a quarter of elderly at postmortem. ATTR is found in 13–19% of people experiencing heart failure with preserved ejection fraction, making it a very common form of systemic amyloidosis.

Research
Treatments for ATTR-related neuropathy include TTR-specific oligonucleotides in the form of small interfering RNA (patisiran) or antisense inotersen, the former having recently received FDA approval. Research into treatments for ATTR amyloidosis have compared liver transplantation, oral drugs that stabilize the misfolding protein (including tafamidis and diflunisal), and newer therapeutic agents still being investigated (including patisiran).  Based on available research, liver transplant remains the most effective treatment option for advanced ATTR amyloidosis, protein stabilizing drugs may slow disease progression but were insufficient to justify delay of liver transplant, and newer agents such as patisiran require additional studies.

See also
 Peptide synthesis
 Proteinopathy

References

External links

Protein folding
Wikipedia neurology articles ready to translate
Skin conditions resulting from errors in metabolism
Wikipedia medicine articles ready to translate

Amyloidosis