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Andreas Isaksson

Jan Andreas Isaksson (born 3 October 1981) is a Swedish former professional footballer who played as a goalkeeper.

Isaksson began his career at local Trelleborgs, before briefly representing Juventus. He would later return to Sweden, where he won two Allsvenskan titles with Djurgården. After two seasons with Rennes, he was signed for £2 million by Manchester City of the Premier League, where he was not a regular. After four seasons in the Eredivisie with PSV, he joined Kasımpaşa in Turkey on a free transfer in 2012. He returned to Djurgårdens IF in 2016 with which he won the 2017–18 Svenska Cupen before retiring in 2018.

Isaksson earned 133 caps for the Sweden national team during his international career, which puts him joint-third in their list of most capped national players of all time together with Sebastian Larsson. He was included in the Swedish squads for the 2002 and 2006 FIFA World Cups as well as the 2004, 2008, 2012, and 2016 UEFA European Championships.

Early career
Born in Smygehamn, Isaksson began his senior career with Trelleborgs, where he played two seasons 1998 and 1999. He became known as a great goalkeeping prospect and was thus bought by Italian club Juventus in July 1999, but with the likes of Dutch international goalkeeper Edwin van der Sar in the squad, Isaksson never played a first-team game for the Turin-based club.

In January 2001, Isaksson signed with Stockholm-based Djurgården in order to play first-team football. In his first two full seasons, in 2002 and 2003, Djurgården won two-straight Swedish titles as well as the cup in 2002. He was voted best Swedish goalkeeper for four consecutive years from 2002 to 2005.

In July 2004, French club Rennes signed him to replace Petr Čech, and he became the starting goalkeeper.

Manchester City
After the 2006 FIFA World Cup, Isaksson completed a £2 million move to Manchester City of the Premier League on 15 August 2006. He was expected to replace David James as their first choice goalkeeper, but due to knee and ankle injuries and the form of Nicky Weaver, he did not achieve this. He made his debut on 9 December 2006, when he replaced the injured Weaver at half-time in a Manchester derby match which City lost 3–1 to Manchester United. After his second start for City on 14 March 2007, he played all of the remaining ten games of 2006–07, keeping four clean sheets, and saved a penalty kick from Jermain Defoe on the last day of the season, although City nonetheless lost 2–1 to Tottenham Hotspur.

Isaksson played the majority of City's next pre-season campaign in Sweden and Belgium, but after his thumb was fractured in a training session, he did not play for City in the first two months of 2007–08, picking up a knee injury right afterwards. Isaksson made his first appearance of the season for Manchester City by keeping a clean sheet in a 1–0 away win against Bolton Wanderers to put the team into the quarter-finals of the League Cup, on 31 October 2007. In November and December. he had a run of five league games in the first team, as part of a rotation used by manager Sven-Göran Eriksson to decide upon his first-choice goalkeeper. His run, however, was ended by an injury. While he was out, England under-21 goalkeeper Joe Hart took over in goal and impressed. The youngster kept his place even after Isaksson returned to full fitness and the Swede was once again relegated to the bench.

Manchester City confirmed that they would be willing to sell Isaksson at the end of the season, and his final appearance was in the humiliating 8–1 defeat by Middlesbrough, which would have been even worse if not for several excellent saves by Isaksson.

PSV
Isaksson signed for Dutch champions PSV, thus enabling him to play in the UEFA Champions League. He took over the number 1 shirt from Heurelho Gomes, who had transferred to Tottenham. Isaksson tallied 124 league appearances for PSV before leaving the club in the summer of 2012 when his contract expired.

Kasımpaşa
On 9 July 2012, it was confirmed that Isaksson had left PSV after four seasons to join newly promoted Turkish side Kasımpaşa on a free transfer. On joining the club, Isaksson signed a three-year deal and became the Turkish side's sixth signing during the summer transfer window.

Return to Djurgårdens
On 11 August 2016, Isaksson signed a two-and-a-half-year contract with Djurgården, returning after 12 years away from Sweden and the club. On 24 August, he played his first game in his second spell for Djurgårdens in the Swedish Cup qualifier, a 5–1 win against Smedby. He conceded one goal in the final minute from a penalty. On 7 August 2017, Isaksson made his 100th match in Allsvenskan for Djurgårdens. On 10 May 2018, he played as they beat Malmö 3–0 in the Swedish Cup Final.

International career
While at Djurgården, Isaksson established himself as the second-choice goalkeeper after Magnus Hedman for the Sweden national team, making his international debut against Switzerland in March 2002. An injury to Hedman allowed Isaksson the opportunity to play for Sweden on a regular basis, playing in all but one of Sweden's qualifying matches for UEFA Euro 2004, and all of Sweden's matches during the tournament.

Isaksson remained the first-choice goalkeeper for his national team since Euro 2004, making three appearances in the 2006 FIFA World Cup in Germany. An injury prevented him from playing in more games. By July 2006, he had amassed 42 caps for his country.

Isaksson was selected for Sweden's Euro 2008 squad, and appeared in all three of Sweden's group games. He kept a clean sheet in Sweden's first match against Greece, which ended 2–0, but Sweden were unable to reach the quarter-finals.

Isaksson was also the first-choice goalkeeper through Sweden's disappointing qualification campaign for the 2010 World Cup in South Africa as well as the qualifying rounds for Euro 2012 in Poland and Ukraine. On 29 May 2012, national team manager Erik Hamrén announced his final 23-man squad for the Euros, including the vastly experienced Isaksson. Isaksson again appeared in all three group games as Sweden failed to make it out of the group, although he did keep a clean sheet in their 2–0 victory over France in the final match.

On 12 October 2012, in a World Cup qualifier in Tórshavn, Isaksson earned his 100th international cap while Sweden defeated the Faroe Islands 2–1.

After Sweden's disappointing Euro 2016 performance, in which Sweden once again failed to progress from the group, Isaksson announced his intention to retire from international football. He amassed 133 caps for his country, effectively making him their third most capped player.

Coaching career
In 2019, Isaksson became goalkeeping coach for Fagersta Södra. He had the role until end of 2020. In April 2022, he was appointed goalkeeping coach of Djurgårdens women's team. After the 2022 Damallsvenskan season, he left the club.

Honours
Djurgårdens
 * Allsvenskan: 2002, 2003
 * Svenska Cupen: 2002, 2017–18

PSV Individual
 * KNVB Cup: 2011–12
 * Johan Cruijff Shield: 2008
 * Årets komet: 1999
 * Swedish Goalkeeper of the Year: 2002, 2003, 2004, 2005, 2009, 2011, 2012, 2013, 2014, 2015
 * Årets Järnkamin: 2018

title: Andreas Isaksson


text: User talk:61.95.133.170

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

title: User talk:61.95.133.170


text:
Talk:Maximum wage

Monetarism
I agree that "economists of the mainstream, if not dominant, Monetarism view, would say"..."inflation is controlled by the growth in the money supply according to the quantity theory of money" is general knowledge, but would like a citation for the idea that they "would say such an argument is entirely incorrect". Also, I agree that "There are no serious mainstream groups advocating a maximum wage" is general knowledge, but would like a citation for "most economists would say a maximum wage is harmful and unenforceable." Personally, I think the former questionable statement is a bit more of an abstract assertion than the latter. (Gamerider 01:32, 6 December 2006 (UTC))

 * You have a point and I took out the second statement. (Though I think it a maximum wage is harmful and unenforceable), but I stand by the first statement. No serious groups advocate a max wage (for good reason), and I think the biggest mistake this article could make is to not challenge the kind of sloppy economic assertions made by supporters who first wrote this article.  The closest relatives of a maximum wage are confiscatory level marginal tax rates and the policy of wage and price controls.  Wage and price controls have been attempted in order to control inflation, but they have never sustainably worked which is why modern economies no longer attempt them.  The last go the US had at wage and price controls to control inflation was in the 1970s under Nixon, and it ended in failure.  As for the other comparison, the top marginal tax rate was significantly higher in the 60s and the 70s than it is now (the top marginal rate was reduced by tax cuts from President Kennedy, tax cuts from President Reagan, and tax reform by the 1986 tax act that reduced the rate but removed exemptions), but inflation is now significantly lower, mostly as a result of a different approach to federal reserve policy started by Paul Volcker and continued by Alan Greenspan (policies that were consistent with Monetarism).  Inflation has dropped to unprecedented low levels worldwide because of the growing trend of independent central banks with central bankers that have an understanding of modern economics and a tough approach to fighting inflation.  The remarkably low inflation the world is experiencing has nothing to do with maximum wage laws.    Mgunn 06:22, 6 December 2006 (UTC)

The 16:59, 5 December 2006 edit was made by me. I forgot to log in before making the edit, which was mostly gramatical, but don't want peope cap, but lawmakers did write into law a top tax rate of 94 percent on all income over $200,000.

A full discussion of maximum wage advocacy in the United States appears in Greed and Good: Understanding and Overcoming the Inequality That Limits Our Lives, by Sam Pizzigati (The Apex Press, 2004).

Things like "The minimum wage concept is an effective tool which can help limit the possibility of deflation of a currency or overall economy." or "The working populous in an economy that has both a minimum and maximum wage is therefore bound to live in the middle of the two economic wage points. Although the benefits of such an arrangement are argued by most economists, historians generally agree that a strong middle class has been key to strong economies throughout history." are really problematic for this article.

 * Thanks!
 * I’ve added Pizzigati to the references and included some content in the body in this edit and earlier ones; I’ve also added the 1942 war-time maximum income proposal by Franklin D. Roosevelt to the same (History) section, together with the implemented policy (88% tax, plus 5% “Victory Tax” = 93%, though 5% credited after the war).
 * —Nils von Barth (nbarth) (talk) 07:20, 9 December 2011 (UTC)

Worked for post-WWII Japan
General MacArthur instituted a maximum wage in Japan.

-Ben Reppulst

No attention to the most obvious feature?
I would have thought the most obvious problem of a 100% tax is that there is zero incentive to make any more money, and therefore it would be pointless from the point of view of attempting to raise revenue to redistribute wealth. This clearly deserves a mention in here, probably pointing to the Laffer Curve. -Nichlemn 10:43, 9 December 2005 (UTC)

I have deleted the following sentence because it it obviously untrue: "A maximum wage would theoretically help governments redistribute wealth to the lower classes." Of course the reverse is true.

CSMR 15:32, 25 September 2006 (UTC)

^^^ question, which may be answered by anybody,, if there were to be a say 5 million$ max wage,, and anything above this would be taxed and put towards helping education, hunger, poverty, free medicare, etc. isnt that in itself an incentive??? i mean if i made more money in a year than i could spend in a lifetime, like some of these ceos, entertainers, and athletes do,, then i would only work for a year and never work again if money was my only incentive. but obviously, guys like tiger woods, who has no need for money (and by economist logic, no incentive) continue to work. So basically my question is that, #1 if money is being equated to incentive to work" by economists, even at the highest levels, then explain to me why bill gates still works??? if the gov told bill gates he could only earn 5 mil per year is he gonna be insulted and walk away from microsoft??(yes theres sarcasm in this question, but i would really like an answer)  and #2 what other arguements are there against a max wage besides incentive?? cause thats the only one ive been able to find and obviously i am not convinced by it.

 * Well, consider, if someone had "helping others" as an incentive, and so would gladly work with 100% of their incomes taxed, you would expect that they'd be donating that income anyway without the effect of the tax. So the "selfish" person who earns money and gives none of it away will concurrently not work with 100% tax, not considering where the tax dollars could be spend. Therefore, a 100% tax would not provide any net "generosity". - Nichlemn

^^ good answer

I would quit, read Atlas Shrugged.

In answer to this question, Bill Gates may not walk away from Microsoft but he would have less incentive to act with so much drive and ambition.

 * If Bill Gates was not allowed to make more than $5mil/year AND all of his competitors were subject to the same limit (which is the point of a maximum wage law) competition would go on unhindered. Just because Bill Gates couldn't make more than $5mil/year doesn't mean Microsoft couldn't make more than that, it just can't give more than $5mil/year to any one person. Investors would still want a company to grow.131.174.91.179 (talk) 15:01, 7 June 2013 (UTC)

Regarding the small changes I have made, plus a question
I would like to note that my changes, while mostly grammatical, did also encompass some factual data. Mostly, this was in regards to how that factual data was represented. I have reworded the article as to avoid vague groups like "supporters" except in reference to actual theoretical camps. Example: Rather than saying "Supporters believe that the maximum wage concept..." I have instead changed the words to read "It is believed that the maximum wage concept...". However, I have left words like "supporters" in sentences like "supporters argue that..." due to the fact that the argument is made by the supporters of the concept; this is not the case for the example I have displayed above. I also have removed all references to a "they" or "them", as this locus is unacceptable without first introducing a group to which "they" or "them" refers.

It is my request that the sentence "This, supporters argue, is advantageous due to the fact that most economists agree that strong economies are supported by a strong middle class", although not directly tied to the Implementation (the subject under which the sentence can be found) of the maximum wage, be left in place until such time as either I or someone else writes a "Support for the maximum wage" or similarly titled and subjected section in response to the criticisms already present in this article.

1. your revision seems like it gives factual creedance to the maximum wage rather than a neutral view. 2. no economists would argue you build a middle class by putting a maximum wage in effect. 3. that last sentence is original research and poorly constructed...and repeat point 2. (Gibby 16:42, 8 February 2006 (UTC))

I, obviously, agree with you that the final sentence, which I proposed keeping, does offer a viewpoint that gives credence to the maximum wage view rather than to a neutral viewpoint. I believe my reason for wanting to keep the sentence was reasonable in the effect that it would be removed at a later date; however, since wikipedia is supposed to carry with it a neutral viewpoint I will not argue about the removal of that sentence.

My other grammatical changes, however, did not bring the article closer to supporting maximum wage; I argue that your grammatical structure gives credence to those camps which are against the maximum wage. I believe that by removing references to specific loci without referencing a specific group or person is unacceptable in a neutral-point article. This article is not meant to represent the viewpoint of abstract groups. If you wish to leave your version of wording I recommend referencing which specific group of supporters you are talking about. Otherwise, the more neutral wording of "it is believed" should be left intact. Moreover, I am shocked that you would revert the page back to its original form without a general consensus on the mater first being collected, and am shocked even more so by the fact that you did not leave the changes to glaring grammatical errors (IE "supporters of the maximum wage is theorize" is an unacceptable sentence to leave unchanged).

I would also like to point out that there are economists who would argue that placing both a minimum and maximum wage upon a society would place all people within that system between the two wage points. Whether or not this would lead to a middle class or a polarized upper and lower class is undetermined; however, I did not specifically state that economists argue that such an action would occur. I merely pointed out that supporters of the maximum wage concept believe that a middle class would be created, and that economists believe that a strong middle class is essential to a strong economy. Both of these points are neither speculation or original; they are fact. Although you may disagree with these facts, I find it unacceptable that you changed them without first consulting the issue and giving me a chance to respond. (Gamerider)

There are no economists that argue that placing maximum and minium wages will result in a society of middle class because that is retarded and an economic fallacy. period. Nor does having a middle class and only a middle class constitute a strong economy. (Gibby 06:28, 10 February 2006 (UTC))

I have reverted the article and have placed an NPOV dispute warning at the top of the page. In the future, please deal with arguments like this by adding this or similar warnings rather than deleting entire articles. I have also nominated this article to be checked by a third party for neutrality, as we seem to be getting nowhere in our arguments.

The notion of a middle class society resulting from both a minimum and maximum wage being implemented is a legitimate theoretical outcome. Furthermore, saying that the theorized outcome "is retarded" is not an argument, nor does it support your argument stating that its an economic fallacy. It is not an economic fallacy that a society, being constricted to living within two wage points, would end up living somewhere in the middle of those wage points. Whether or not this results in a middle class is disputed, as the possibility of a economically polarized society (where there is only a very rich and a very poor class) is apparent as well.

I have changed my statement that economists believe a strong middle class constitutes a strong economy to actually say what it said in the first place: that historians believe a strong middle class constitutes a strong economy. This is an effect that we have seen throughout history; in many different civilizations throughout the world. (Gamerider)

Jiminy Christmas! "A legitimate theoretical outcome" maybe if theoretical outcomes are not supposed to be predictive of events in the actual world. Let us be clear here. The idea that the result of both a minimum and maximum wage would be a society entirely composed of middle class is not a legitamate outcome of ECONOMIC theory.

Furthurmore, if you are going to state that historians believe that a strong middle class constitutes a strong economy you'd better site your sources. Historians of economics would not subscribe to such a ludicrous blanket statement. The fact is economy such as preasent day United States would be considered "stronger" by just about any historian than that of a neolithic tribesman, despite the fact that most of the members of that society were likely "middle class." Factually, in many ways the poorest citizens of modern industrialized nations are materially better off than juust about any human being that has ever lived. Economist tend to view things such as standards of living to be the best ways of evaluating the health of an economy, not merely the distribution of income levels.

-jglassman

It is only a legitimate outcome in fairyland. If you put a maximum wage you will end up with a society of poor, not middle class. The assumption is completly silly. (Gibby 17:01, 15 February 2006 (UTC))

 * It should be rather obvious that when people say things like that having a large, strong middle class is good for an economy they mean it is good compared to another economy with the same means, so Sweden in 2013 does better than Brazil in 2013 (GDP/capita, hdi, life expectancy, corruption index, crime levels, social mobility, etc...) and an egalitarian neolithic tribe does better than a neolithic tribe with a privileged nobility.

 * Also, any economist worth his salt would not say standard of living only depends on material wealth only, especially not in the narrow sense of physical goods. Writing that John Rockefeller didn't have a mobile phone or a TV so today's working poor are better off than him is something WSJ columnists do to make themselves feel better, real economists know Rockefeller could buy every one in congress and the senate many times over, could go to bed with a different set of 7 beautiful women every night, could pay for people to carry him around in a throne all day, could hire entire armies of servants, could hire the best lawyers in the world and pay even the highest fines without feeling it, he could buy vast amounts of real estate and had the social status that comes with being one of the richest men in the world, so that mobile phone and TV are a bit insignificant in comparison. It would be nice if the level here could be more real economist and less WSJ 1%-stooge columnist.89.99.122.33 (talk) 00:27, 2 August 2013 (UTC)

Added history from Department of Labor website
I added some information from the government Department of Labor website. There is no opinion in there, just a statement of its existence in those times and the sources reference specific laws and state instances. I see no reason to argue over what the effects of maximum wage laws have to be- they are what they are. If they are in effect they can be used for many different rationals. The minimum wage article isn't being disputed as biased, what's so complicated here?

Please
Who wrote the opening paragraphs of this article? One of the topics of highest agreement among professional economists (read, not wanna-be socialists who took high school economics) is the connection between increases in the supply of high powered money and inflation. I'm sorry, but high wages alone do not create inflation. I would like someone to walk me through an economy where the high powered money supply is fixed, and the advent of high wages, or rising wages in some sectors or for some individuals results in economy-wide inflation. It just dosen't happen. The opening paragraphs of this article are irresponsible. They are a fantasyland excuse for implementing a maximum wage. While I am against a maximum wage law, I do admit that some of the arguments presented have some truth, such as the ability of wage controls to equalize the wealth distribution. (I would point out that price controls do equalize wealth - we all tend to be poorer). However, advocating wage controls as a method to prevent changes in the valuation of currency is pure fantasy; this simply does not happen without changes brought about by central banks in the money supply.

In addition, a valid but overlooked criticism of this policy is that it is totally unenforcable. The United States has outlawed most drugs, prostitution, and many forms of sports betting. However, these activites still occur in black markets throughout the nation, and the world for that matter. I find it hard to believe that the government would be able to enforce maximum wage/wealth laws without an army of investigators, enforcers, prosecutors, and the like. The US has a global army employed in the fighting of narcotics trafficing and by the IRS to investigate tax compliance. All the resources placed in these enforcement roles are essentially wasted - drugs are readily available in the US and tax avoidance couldn't be easier. It could be argued that the deadweight loss placed upon high wealth generating activites by this form of extremely progressive taxation would be more burdensome and unattractive than the original conditions which prompted such a policy.

-Md Economist

 * I just came across this article and at least challenged some of the most doubtful assertions (I probably should have deleted them, anyway, I didn't). Hopefully the article imparts a more proper understanding now. Mgunn 18:57, 29 November 2006 (UTC)

 * Enforcement would require the elimination of cash money and direct linking of accounts to a person with an automated limit for how much money any one person can receive in a year. Not impossible, but it would require major changes to financial systems. Of course fraud could still take place by people buying themselves a car via their business or the payment of bribes in cars and gold, but this would all be limited and be punishable by jail time (large settlements to stay out of jail wouldn't exist anymore because no one is supposed to be rich anymore). P.S. the stuff about inflation does indeed not make a lot of sense and even if it's true it shouldn't be the main selling point, the main selling point should be the limitation of income and wealth inequality and the positive effects that would have for anyone who's not in the 1%.89.99.122.33 (talk) 00:54, 2 August 2013 (UTC)

Rewrite / Delete?
I think most of the material in here is just bogus/wrong, and it sounds like much of the article was written by a high school economics student. I generaly avoid deleting wide swathes of text, but much of this articleprobably warrants it. I think the main points are: (1) explain what a maximum wage is (2) Some economists used to view wage controls as a way to fight inflation... this view is quite discreditted (3) no serious group advocates a maximum wage. If there are no objections, I'll redo the article. Mgunn 21:20, 15 January 2007 (UTC)

 * One point nobody has noted is that not all wage ceilings are enforced by governments. Professional sports leagues like the Victorian Football League used to impose rigid wage ceilings on players (the Coulter Law) to help even the competition. This would need discussion of the article is improved luokehao 6:48, 16 November 2008 (UTC)

Some other things to consider in a rewrite
I would like to point out that a rewrite of the page, the benefits of a maximum wage should be pointed out. Granted it doesn't do much for the numbers of an economy on the whole, but it does help out decrease the gap between rich and poor, and a high rich-poor gap is damaging to other parts of the society. Also, the current article only seems to really delve into things from the theories of Monetarism. Although dominant, Monetarism has definitely been shown not to be the most accurate theory on economics. (That title belongs, if I recall correctly, to Creative destruction, at having the highest accuracy rating at prediction economic trends than any other theory).

Obama maximum wage
I heard today that Obama is going to limit corporate earnings in his aid packages. http://www.google.com/hostednews/ap/article/ALeqM5iYX--wRrv7CQhjxb9FFjidsIvjLQD964VDDG0 should this be included in the article? wiesel (talk) 20:56, 4 February 2009 (UTC)

Should the Laffer Curve be discussed in this article?
I was wondering if the article should discuss the disincentives for governments to impose a maximum wage or have extremely high tax rates for the highest marginal rate because according to the laffer curve you want to tax income at the point where government tax revenue is maximized. In addition, in the 1990s the highest federal tax rate in the U.S. was 39.6% for personal income taxpayers and in addition interest rates (federal funds rate) were low because Alan Greenspan recognized the productivity revolution that began in 1995 compelling him to set low interest rate targets for the federal funds rate. Basically, tax rates and interest rates were low during the 1990s and the commodity price level was much lower in the 1990s versus the 2000s, signifying that in certain instances when income is not taxed in a punitive manner, but maximized to maximize government tax revenue, you do not need a maximum wage but sound fiscal and monetary management of the economy to reduce inflation, and promote greater economic growth and government revenue. Someone please respond to these comments to induce further discussion on the subject.65.110.146.154 (talk) 21:27, 16 February 2009 (UTC)

 * A maximum income law does not mean total taxation as a percentage of GDP has to increase. If you tax everyone 100% above say, $1 million per year, this will affect less than 0.5% of people (in the US) you can use the additional tax income to lower taxes on the other 99.5% of people (if you eliminated all taxes for income below $1 million you could bring down total taxation to something like 10% of GDP, so don't worry about that Laffer Curve). So for every person who has to pay more taxes 199 people end up paying less taxes and it is well known from psychology that going from a net income of $30k to one of $40k is much more motivating than any income beyond $1 million. To disagree with this you'd have to deny every psychological study on the subject AND you'd have to believe the richest 0.5% are supermen who produce more value than 199 ordinary people combined.89.99.122.33 (talk) 00:35, 31 July 2013 (UTC)

Related concepts...?
"Maximum Total Earnings legislation suggests that when a person has accumulated sufficient wealth that they can survive on the interest alone they must stop working and allow someone else to work. This theoretical concept assumes there is a set amount of work to be done in an economy, and is not supported by any major form of modern economic thought. Attempts to reduce unemployment by removing people from the labor force, as is proposed by this theory, have been a failure.[citation needed]"

This reeks of NPOV problems. Also, what are the related concepts supposed to be? :-P I propose deletion, if not of the entire section at least this text and insertion of actual related concepts/topics by name. Nlalic (talk) 19:01, 21 July 2012 (UTC)

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title: Talk:Maximum wage


text:
Catena

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title: Catena


text:
Autoimmune hepatitis

Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. Common initial symptoms may include fatigue, nausea, muscle aches, or weight loss or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease may be detected by abnormal liver function tests and increased protein levels during routine bloodwork or the observation of an abnormal-looking liver during abdominal surgery.

Anomalous presentation of MHC class II receptors on the surface of liver cells, possibly due to genetic predisposition or acute liver infection, causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis. This abnormal immune response results in inflammation of the liver, which can lead to further symptoms and complications such as fatigue and cirrhosis. The disease is most often diagnosed in patients in their late teens or early 20s and between the ages of 40 and 50. It affects women more commonly than men.

Signs and symptoms
Autoimmune hepatitis may present completely asymptomatic (12–35% of the cases), with signs of chronic liver disease, or acute or even fulminant hepatic failure.

People usually present with one or more nonspecific, long-lasting symptoms such as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant abdominal pain, malaise, anorexia, itching, nausea, jaundice or joint pain especially affecting the small joints. Rarely, rash or unexplained fever may appear. In women, the absence of menstruation (amenorrhoea) is a frequent feature. Physical examination may be normal, but it may also reveal signs and symptoms of chronic liver disease. Many people have only laboratory abnormalities as their initial presentation, as unexplained increase in transaminases and are diagnosed during an evaluation for other reasons. Others have already developed cirrhosis at diagnosis. Of note, alkaline phosphatase and bilirubin are usually normal.

Autoimmune hepatitis may overlap with other autoimmune conditions, mainly type 1 diabetes mellitus, ulcerative colitis, lupus, celiac disease, vasculitis, and autoimmune thyroiditis.

Cause
The prevailing theory for the development of autoimmune hepatitis is thought to be the interplay of genetic predisposition, an environmental trigger (virus, drugs, herbs, immunizations), and failure of the native immune system resulting in chronic inflammation of hepatocytes and subsequent fibrosis of the liver.

There is no specific evidence of the cause. Sixty percent of patients have findings associated with chronic hepatitis but without serologic evidence of a viral infection. The disease is strongly associated with anti-smooth muscle autoantibodies.

The exact genes and triggers responsible remain undefined, but studies show association of early-onset, severe disease with the HLA-DR3 serotype and late-onset disease with the HLA-DR4 serotype.

Diagnosis
The diagnosis of autoimmune hepatitis is best achieved with a combination of clinical, laboratory, and histological findings after excluding other etiological factors (e.g. viral, hereditary, metabolic, cholestatic, and drug-induced liver diseases). The requirement for histological examination necessitates a liver biopsy, typically performed with a needle by the percutaneous route, to provide liver tissue.

Autoantibodies
A number of specific antibodies found in the blood (antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver kidney microsomal antibodies (LKM-1, LKM-2, LKM-3), anti soluble liver antigen (SLA), liver–pancreas antigen (LP), and anti-mitochondrial antibody (AMA)) are of use, as is finding an increased immunoglobulin G level. The presence of anti-mitochondrial antibody is more suggestive of primary biliary cholangitis. Hypergammaglobulinemia is also of diagnostic value.

Histology
Autoimmune hepatitis can be characterized histologically by the following nonspecific findings:
 * Portal mononuclear cell infiltrate that invades the boundary surrounding the portal triad and infiltrates the surrounding lobule.
 * Periportal lesions, also known as interface hepatitis, that spare the biliary tree (may include centrizonal necrosis).
 * Bile duct abnormalities (cholangitis, ductal injury, ductular reaction) can be seen and should prompt evaluation for primary biliary cholangitis or sarcoidosis if granulomas are observed.
 * Plasma cell infiltrate, rosettes of hepatocytes, and multinucleated giant cells.
 * Varying degrees of fibrosis (except in the mildest form of autoimmune hepatitis). Bridging fibrosis that connects the portal and central areas can distort the structure of the hepatic lobule and result in cirrhosis.

Diagnostic scoring
The Internal Autoimmune Hepatitis Group developed a standardized scoring system for clinical diagnosis in population studies but lacks value in individualized cases. A simplified scoring system for clinical use incorporates titers of autoantibodies, total IgG levels, liver histology, and the exclusion of viral hepatitis for diagnostic scoring.

Classification
On the basis of detected autoantibodies, autoimmune hepatitis can be classified into three subtypes but have no distinct clinical presentations.
 * Type 1 autoimmune hepatitis. Positive antibodies include:
 * Antinuclear antibody (ANA)
 * Anti-smooth muscle antibody (ASMA) - 65% of people
 * Anti-actin antibodies
 * Anti-mitochondrial antibodies - rare except for overlap syndromes with primary biliary cholangitis
 * Anti-soluble liver antigen/liver pancreas antibody antigen - 20% of people
 * Anti-double stranded DNA - 30% of people
 * Atypical perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)
 * Type 2 autoimmune hepatitis. Positive antibodies include:
 * Liver Kidney Microsomal antibody (LKM-1)
 * Anti-liver cytosol antibody-1 (SLC-1)
 * Autoantibody negative autoimmune hepatitis.
 * Lack positive ANA, ASMA, LKM-1, etc. antibody panels but present with clinical features of autoimmune hepatitis that resolve with standard treatment.

Differential diagnosis
Other diagnoses to consider include conditions that may cause acute hepatitis or chronic liver inflammation that may be accompanied by cirrhosis:
 * Other autoimmune diseases that involve the liver:
 * Primary biliary cholangitis - the presence of isolated elevated AMA antibodies usually signifies primary biliary cholangitis rather than autoimmune hepatitis and further diagnostic evaluation is needed.
 * Overlap syndromes - autoimmune hepatitis may present similarly to primary sclerosing cholangitis but people with primary sclerosing cholangitis have stricturing and dilatation of intra/extra-hepatic ducts while people with autoimmune hepatitis generally have a spared biliary tree.
 * Other causes of hepatitis:
 * Viral hepatitis - it is necessary to distinguish autoimmune hepatitis from acute hepatitis caused by Hepatitis A/B/C/D/E, herpes simplex, varicella zoster, EBV, CMV virus
 * Drug-induced liver injury - portal neutrophils are more prevalent in drug-induced liver injury on liver biopsy and can help distinguish the two
 * Nonalcoholic steatohepatitis - related medical history and liver biopsy showing fatty infiltration and the presence of neutrophils and central fibrosis can distinguish the two
 * Lupus-associated liver disease - rarely presents with elevated ASMA or AMA antibodies
 * Acute liver failure - people with acute liver failure may have elevated autoantibodies but the antibodies alone are not enough for the diagnosis of autoimmune hepatitis
 * Iron overload - elevated iron in the body can cause liver inflammation

Treatment
The choice for medical treatment should be based on the individual's severity of symptoms, quantitative elevation of liver enzymes and antibody levels, findings on liver biopsy, and ability to tolerate side effects of medical therapy.

Generally, treatment is not required in asymptomatic patients with normal liver enzyme and antibody levels and liver biopsies that do not demonstrate inflammation because these patients are at a low risk of disease progression. In symptomatic individuals with evidence of interface hepatitis and necrosis on liver biopsy, it is recommended to offer treatment especially if the patient is young and can tolerate the side effects of medical therapy. In addition, some authorities recommend treating every patient with a diagnosis of autoimmune hepatitis, even if they are asymptomatic for a long period of time.

The mainstay of treatment involves the use of immunosuppressive glucocorticoids such as prednisone during acute episodes and resolution of symptoms can be achieved in up to 60–80% of cases, although many will eventually experience a relapse. In individuals with moderate to severe disease who may not tolerate glucocorticoids, lower dose prednisone monotherapy or combination with azathioprine is a reasonable alternative. Budesonide has been shown to be more effective in inducing remission than prednisone, but evidence is scarce and more data is needed before it can be routinely recommended. Those with autoimmune hepatitis who do not respond to glucocorticoids and azathioprine may be given other immunosuppressives like mycophenolate, ciclosporin, tacrolimus, or methotrexate.

Liver cirrhosis can develop in about 7% to 40% of treated patients. People with the highest risk for progression to cirrhosis are those with incomplete response to treatment, treatment failure, and multiple relapses. Once cirrhosis develops, management of liver cirrhosis in autoimmune hepatitis is standard regardless of etiology. Liver transplantation is the standard of care in people presenting with fulminant liver failure or those with the progression of disease despite multiple lines of therapy.

Many patients, once started on long-term immunosuppressive therapy, will remain on that treatment for life. Common practice is to discontinue immunosuppressive therapy after two or more years of normalized transaminases and IgG. However, approximately 90% of patients with autoimmune hepatitis will relapse after treatment has been stopped. As a result, some specialists advocate for permanent immunosuppressive therapy in some patients.

Prognosis
Without treatment, the ten-year survival rate for individuals with symptomatic autoimmune hepatitis is 50%. However, with treatment, the ten-year survival rate is above 90%. Despite the benefits of treatment, people with autoimmune hepatitis generally have a lower transplant-free survival than the general population. Outcomes with liver transplant are generally favorable with a five-year survival greater than 80 percent.

Presentation and response to therapy may differ according to race. African Americans appear to present with a more aggressive disease that is associated with worse outcomes.

Epidemiology
Autoimmune hepatitis can develop in people of any race or age but occurs most frequently in women. Eighty percent of cases are the type 1 subtype with women being affected 4 times more often than men; for the type 2 subtype, women are affected 10 times more often than men.

European studies suggest a disease incidence of 1 to 2 people affected per 100,000 population with a prevalence of 10 to 25 people per 100,000 population.

The disease has a bimodal peak occurring between the ages of 10 and 20 and then later in life between the ages of 40 and 50.

History
Autoimmune hepatitis was previously called "lupoid" hepatitis due to people having an associated autoimmune disease like system lupus erythematosus at time of diagnosis, which was believed to be its cause. It was originally described in the early 1950s.

title: Autoimmune hepatitis


text:
Doxycycline

Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis. It is also used to prevent malaria. Doxycycline may be taken by mouth or by injection into a vein.

Common side effects include diarrhea, nausea, vomiting, abdominal pain, and an increased risk of sunburn. Use during pregnancy is not recommended. Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production. It kills malaria by targeting a plastid organelle, the apicoplast.

Doxycycline was patented in 1957 and came into commercial use in 1967. It is on the World Health Organization's List of Essential Medicines. Doxycycline is available as a generic medicine. In 2021, it was the most commonly prescribed medication in the United States, with more than 8million prescriptions.

Medical uses
In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease, severe acne, rosacea,   and rickettsial infections. The efficiency of oral doxycycline for treating papulopustular rosacea and adult acne is not solely based on its antibiotic properties, but also on its anti-inflammatory and anti-angiogenic properties.

In Canada, in 2004, doxycycline was considered a first-line treatment for chlamydia and non-gonococcal urethritis and with cefixime for uncomplicated gonorrhea.

General indications
Doxycycline is a broad-spectrum antibiotic that is employed in the treatment of numerous bacterial infections. It is effective against bacteria such as Moraxella catarrhalis, Brucella melitensis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Additionally, doxycycline is used in the prevention and treatment of serious conditions like anthrax, leptospirosis, bubonic plague, and Lyme disease. However, some bacteria, including Haemophilus spp., Mycoplasma hominis, and Pseudomonas aeruginosa, have shown resistance to doxycycline. It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease,   ehrlichiosis,  and Rocky Mountain spotted fever.

Specifically, doxycycline is indicated for treatment of the following diseases:
 * Rocky Mountain spotted fever, typhus fever and the typhus group, scrub typhus, Q fever, rickettsialpox, and tick fevers caused by Rickettsia,
 * respiratory tract infections caused by Mycoplasma pneumoniae,
 * Lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis,
 * psittacosis,
 * non-gonococcal urethritis caused by Ureaplasma urealyticum,
 * relapsing fever due to Borrelia recurrentis,
 * chancroid caused by Haemophilus ducreyi,
 * plague due to Yersinia pestis,
 * tularemia,
 * cholera,
 * campylobacter fetus infections,
 * brucellosis caused by Brucella species (in conjunction with streptomycin),
 * bartonellosis,
 * granuloma inguinale (Klebsiella species),
 * Lyme disease: it can be used in adults and children. For treatment or prophylaxis of Lyme disease in children, it can be used for a duration of up to 21 days in children of any age. Doxycycline is specifically indicated to treat Lyme disease for patients presenting with erythema migrans. As for the optimal duation of treatment of this disease, guidelines vary, with some recommending a 10-day course of doxycycline, while others suggest a 14-day course; still, recent data suggest that even a 7-day course of doxycycline can be effective. Compared to other drugs, there are no significant differences in treatment response across antibiotic agents, doses, or durations when comparing 14 days versus 21 days; as such, the optimal duration of treatment of Lyme disease remains uncertain, as prolonged antibiotic courses have drawbacks, including diminishing returns in terms of patient outcomes, heightened risks of adverse events, superinfections, increased healthcare costs, and the potential for development of antibiotic resistance. Therefore, the consensus remains to treat patients with the shortest effective duration of antibiotics, as is the case with doxycycline for Lyme disease as well.

Gram-negative bacteria specific indications
When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-negative bacteria:
 * Escherichia coli infections,
 * Enterobacter aerogenes (formerly Aerobacter aerogenes) infections,
 * Shigella species infections,
 * Acinetobacter species (formerly Mima species and Herellea species) infections,
 * respiratory tract infections caused by Haemophilus influenzae,
 * respiratory tract and urinary tract infections caused by Klebsiella species.

Gram-positive bacteria specific indications
Some Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of Streptococcus pyogenes and up to 74% of S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. Up to 57% of P. acnes strains developed resistance to doxycycline. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria:
 * upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae),
 * skin and soft tissue infections caused by Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus infections,
 * anthrax caused by Bacillus anthracis infection.

Specific applications of doxycycline when penicillin is contraindicated
When penicillin is contraindicated, doxycycline can be used to treat:
 * syphilis caused by Treponema pallidum,
 * yaws caused by Treponema pertenue,
 * listeriosis due to Listeria monocytogenes,
 * Vincent's infection caused by Fusobacterium fusiforme,
 * actinomycosis caused by Actinomyces israelii,
 * infections caused by Clostridium species.

Use as adjunctive therapy
Doxycycline may also be used as adjunctive therapy for severe acne.

Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for periodontitis. Significant differences were observed for all investigated clinical parameters of periodontitis in favor of the scaling and root planing + SDD group where SDD dosage regimens is 20 mg twice daily for three months in a meta-analysis published in 2011. SDD is also used to treat skin conditions such as acne and rosacea, including ocular rosacea. In ocular rosacea, treatment period is 2 to 3 months. After discontinuation of doxycycline, recurrences may occur within three months; therefore, many studies recommend either slow tapering or treatment with a lower dose over a longer period of time.

Doxycycline is used as an adjunctive therapy for acute intestinal amebiasis.

Doxycycline is also used as an adjunctive therapy for chancroid.

As prophylaxis against sexually transmitted infections
Doxycycline is used for post-exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs), but it has been associated with tetracycline resistance in associated species, in particular, in Neisseria gonorrhoeae. For this reason, Australian consensus statement mentions that doxycycline for PEP particularly in gay, bisexual and other men who have sex with men (GBMSM) should be considered only for the prevention of syphilis in GBMSM, and that the risk of increasing antimicrobial resistance outweighed any potential benefit from reductions in other bacterial STIs in GBMSM.

Appropriate use of doxycycline for PEP is supported by guidelines from the US Centers for Disease Control and Prevention (CDC) and the Australasian Society for HIV Medicine.

Use in combination
The first-line treatment for brucellosis is a combination of doxycycline and streptomycin and the second-line is a combination of doxycycline and rifampicin (rifampin).

Antimalarial
Doxycycline is active against the erythrocytic stages of Plasmodium falciparum but not against the gametocytes of P. falciparum. It is used to prevent malaria. It is not recommended alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed.

Doxycycline blocks protein production in apicoplast (an organelle) of P. falciparum—such blocking leads to two main effects: it disrupts the parasite's ability to produce fatty acids, which are essential for its growth, and it impairs the production of heme, a cofactor. These effects occur late in the parasite's life cycle when it is in the blood stage, causing the symptoms of malaria. By blocking important processes in the parasite, doxycycline both inhibits the growth and prevents the multiplication of P. falciparum. It does not directly kill the living organisms of P. falciparum but creates conditions that prevent their growth and replication.

The World Health Organization (WHO) guidelines state that the combination of doxycycline with either artesunate or quinine may be used for the treatment of uncomplicated malaria due to P. falciparum or following intravenous treatment of severe malaria.

Antihelminthic
Doxycycline kills the symbiotic Wolbachia bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis. Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of microfilariae.

Spectrum of susceptibility
Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma, and others. The following represents minimum inhibitory concentration susceptibility data for a few medically significant microorganisms.
 * Chlamydia psittaci: 0.03 μg/mL
 * Mycoplasma pneumoniae: 0.016–2 μg/mL
 * Streptococcus pneumoniae: 0.06–32 μg/mL

Sclerotherapy
Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely venous and lymphatic malformations, as well as post-operative lymphoceles.

Off-label use
Doxycycline has found off-label use in the treatment of transthyretin amyloidosis (ATTR). Together with tauroursodeoxycholic acid, doxycyclin appears to be a promising combination capable of disrupting transthyretine TTR fibrils in existing amyloid deposits of ATTR patients.

Routes of administration
Doxycycline can be administered via oral or intravenous routes.

The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants is not inherently dangerous, but any of these foods and supplements may decrease absorption of doxycycline.

Doxycycline has a high oral bioavailability, as it is almost completely absorbed in the stomach and proximal small intestine. Unlike other tetracyclines, its absorption is not significantly affected by food or dairy intake. However, co-administration of dairy products reduces the serum concentration of doxycycline by 20%. Doxycycline absorption is also inhibited by divalent and trivalent cations, such as iron, bismuth, aluminum, calcium and magnesium. Doxycycline forms unstable complexes with metal ions in the acidic gastric environment, which dissociate in the small intestine, allowing the drug to be absorbed. However, some doxycycline remains complexed with metal ions in the duodenum, resulting in a slight decrease in absorption.

Contraindications
Severe liver disease or concomitant use of isotretinoin or other retinoids are contraindications, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases.

Pregnancy and lactation
Doxycycline is categorized by the FDA as a class D drug in pregnancy. Doxycycline crosses into breastmilk. Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. They include a class warning about staining of teeth and decreased development of dental enamel in children exposed to tetracyclines in utero, during breastfeeding or during young childhood. However, the FDA has acknowledged that the actual risk of dental staining of primary teeth is undetermined for doxycycline specifically. The best available evidence indicates that doxycycline has little or no effect on hypoplasia of dental enamel or on staining of teeth and the CDC recommends the use of doxycycline for treatment of Q fever and also for tick-borne rickettsial diseases in young children and others advocate for its use in malaria.

Adverse effects
Adverse effects are similar to those of other members of the tetracycline antibiotic group. Doxycycline can cause gastrointestinal upset. Oral doxycycline can cause pill esophagitis, particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or impaired mobility. Doxycycline is less likely than other antibiotic drugs to cause Clostridium difficile colitis''. ''

An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug.

Unlike some other members of the tetracycline group, it may be used in those with renal impairment.

Doxycycline use has been associated with increased risk of inflammatory bowel disease. In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's disease.

Interactions
Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to CYP450 induction. Research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.

Pharmacology
Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by preventing bacteria from reproducing through the inhibition of protein synthesis.

Doxycycline is highly lipophilic, so it can easily enter cells, meaning the drug is easily absorbed after oral administration and has a large volume of distribution. It can also be re-absorbed in the renal tubules and gastrointestinal tract due to its high lipophilicity, giving it a long elimination half-life, and it is also prevented from accumulating in the kidneys of patients with kidney failure due to the compensatory excretion in faeces. Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. In addition, food has less effect on absorption than on absorption of earlier drugs with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.

Mechanism of action
Doxycycline is a broad-spectrum bacteriostatic antibiotic. It inhibits the synthesis of bacterial proteins by binding to the 30S ribosomal subunit, which is only found in bacteria. This prevents the binding of transfer RNA to messenger RNA at the ribosomal subunit meaning amino acids cannot be added to polypeptide chains and new proteins cannot be made. This stops bacterial growth giving the immune system time to kill and remove the bacteria.

Pharmacokinetics
The substance is almost completely absorbed from the upper part of the small intestine. It reaches highest concentrations in the blood plasma after one to two hours and has a high plasma protein binding rate of about 80–90%. Doxycycline penetrates into almost all tissues and body fluids. Very high concentrations are found in the gallbladder, liver, kidneys, lung, breast milk, bone and genitals; low ones in saliva, aqueous humor, cerebrospinal fluid (CSF), and especially in inflamed meninges. By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges.

Doxycycline metabolism is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from blood vessels), where some of it is inactivated by forming chelates. About 40% are eliminated via the kidneys, much less in people with end-stage kidney disease. The biological half-life is 18 to 22 hours (16 ± 6 hours according to another source ) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with liver disease.

Chemistry
Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen azotemia due to catabolic effects.

Chemical properties
Doxycycline, doxycycline monohydrate and doxycycline hyclate are yellow, crystalline powders with a bitter taste. The latter smells faintly of ethanol, a 1% aqueous solution has a pH of 2–3, and the specific rotation is $$[\alpha]_D^{25}$$ −110° cm3/dm·g in 0.01 N methanolic hydrochloric acid.

History
After penicillin revolutionized the treatment of bacterial infections in World War II, many chemical companies moved into the field of discovering antibiotics by bioprospecting. American Cyanamid was one of these, and in the late 1940s chemists there discovered chlortetracycline, the first member of the tetracycline class of antibiotics. Shortly thereafter, scientists at Pfizer discovered oxytetracycline and it was brought to market. Both compounds, like penicillin, were natural products and it was commonly believed that nature had perfected them, and further chemical changes could only degrade their effectiveness. Scientists at Pfizer led by Lloyd Conover modified these compounds, which led to the invention of tetracycline itself, the first semi-synthetic antibiotic. Charlie Stephens' group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the FDA in 1967.

As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifier that was not resolved until 1983; at the time it was the largest litigated patent case in US history. Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories.

In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues". Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva (which ceased production in May 2013), Mylan, Actavis, and Hikma Pharmaceuticals. The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time. The market price for doxycycline dramatically increased in the United States in 2013 and early 2014 (from $20 to over $1800 for a bottle of 500 tablets),  before decreasing again.

Society and culture
Doxycycline is available worldwide under many brand names. Doxycycline is available as a generic medicine.

Research
Research areas on the application of doxycycline include the following medical conditions:
 * macular degeneration;
 * rheumatoid arthritis instead of minocycline (both of which have demonstrated modest efficacy for this disease).

Anti-inflammatory agent
Some studies show doxycycline as a potential agent to possess anti-inflammatory properties acting by inhibiting proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinases (MMPs) while increasing the production of anti-inflammatory cytokines such as interleukin-10 (IL-10). Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response. Some studies suggest that doxycycline can suppress the activation of the nuclear factor-kappa B (NF-κB) pathway, which is responsible for upregulating several inflammatory mediators in various cells, including neurons; therefore, it is studied as a potential agent for treating neuroinflammation.

A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of matrix metalloproteinases (MMPs), which are a group of proteases known to regulate the turnover of extracellular matrix (ECM) and thus are suggested to be important in the process of several diseases associated with tissue remodeling and inflammation. Doxycycline has been shown to inhibit MMPs, including matrilysin (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein.

Doxycycline also inhibits allikrein-related peptidase 5 (KLK5). The inhibition of MMPs and KLK5 enzymes subsequently suppresses the expression of LL-37, a cathelicidin antimicrobial peptide that, when overexpressed, can trigger inflammatory cascades. By inhibiting LL-37 expression, doxycycline helps to mitigate these downstream inflammatory cascades, thereby reducing inflammation and the symptoms of inflammatory conditions.

Doxycycline is used to treat acne vulgaris and rosacea. However, there is no clear understanding of what contributes more: the bacteriostatic properties of doxycycline, which affect bacteria (such as Propionibacterium acnes ) on the surface of sebaceous glands even in lower doses called "submicrobial" or "subantimicrobial",   or whether doxycycline's anti-inflammatory effects, which reduce inflammation in acne vulgaris and rosacea, including ocular rosacea, contribute more to its therapeutic effectiveness against these skin conditions. Subantimicrobial-dose doxycycline (SDD) can still have a bacteriostatic effect, especially when taken for extended periods, such as several months in treating acne and rosacea. While the SDD is believed to have anti-inflammatory effects rather than solely antibacterial effects, SDD was proven to work by reducing inflammation associated with acne and rosacea. Still, the exact mechanisms have yet to be fully discovered. One probable mechanism is doxycycline's ability to decrease the amount of reactive oxygen species (ROS). Inflammation in rosacea may be associated with increased production of ROS by inflammatory cells; these ROS contribute toward exacerbating symptoms. Doxycycline may reduce ROS levels and induce antioxidant activity because it directly scavenges hydroxyl radicals and singlet oxygen, helping minimize tissue damage caused by highly oxidative and inflammatory conditions. Studies have shown that SDD can effectively improve acne and rosacea symptoms, probably without inducing antibiotic resistance. It is observed that doxycycline exerts its anti-inflammatory effects by inhibiting neutrophil chemotaxis and oxidative bursts, which are common mechanisms involved in inflammation and ROS activity in rosacea and acne.

Doxycycline's dual benefits as an antibacterial and anti-inflammatory make it a helpful treatment option for diseases involving inflammation not only of the skin, such as rosacea and acne, but also in conditions such as osteoarthritis or periodontitis. Nevertheless, current results are inconclusive, and evidence of doxycycline's anti-inflammatory properties needs to be improved, considering conflicting reports from animal models so far. Doxycycline has been studied in various immunological disorders, including rheumatoid arthritis, lupus, and periodontitis. In these conditions, doxycycline has been researched to determine anti-inflammatory and immunomodulatory effects that could be beneficial in treating these conditions. However, a solid conclusion still needs to be provided.

Doxycycline is also studied for its neuroprotective properties which are associated with antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. In this context, it is important to note that doxycycline is able to cross the blood–brain barrier. Several studies have shown that doxycycline inhibits dopaminergic neurodegeneration through the upregulation of axonal and synaptic proteins. Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration and precede neuronal death in neurodegenerative diseases, including Parkinson's disease (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD. It has been demonstrated that doxycycline mimics nerve growth factor (NGF) signaling in PC12 cells. However, the involvement of this mechanism in the neuroprotective effect of doxycycline is unknown. Doxycycline is also studied in reverting inflammatory changes related to depression. While there is some research on the use of doxycycline for treating major depressive disorder, the results are mixed.

After a large-scale trial showed no benefit of using doxycycline in treating COVID19, the UK's National Institute for Health and Care Excellence (NICE) updated its guidance to not recommend the medication for the treatment of COVID19. Doxycycline was expected to possess anti-inflammatory properties that could lessen the cytokine storm associated with a SARS-CoV-2 infection, but the trials did not demonstrate the expected benefit. Researchers also believed that doxycycline possesses anti-inflammatory and immunomodulatory effects that could reduce the production of cytokines in COVID-19, but these supposed effects failed to improve the outcome of COVID-19 treatment.

Wound healing
Research on novel drug formulations for the delivery of doxycycline in wound treatment is expanding, focusing on overcoming stability limitations for long-term storage and developing consumer-friendly, parenteral antibiotic delivery systems. The most common and practical form of doxycycline delivery is through wound dressings, which have evolved from mono- to three-layered systems to maximize healing effectiveness.

Research directions on the use of doxycycline in wound healing include the continuous stabilization of doxycycline, scaling up technology and industrial production, and exploring non-contact wound treatment methods like sprays and aerosols for use in emergencies and when medical care is not readily accessible.

Research reagent
Doxycycline and other members of the tetracycline class of antibiotics are often used as research reagents in in vitro and in vivo biomedical research experiments involving bacteria as well in experiments in eukaryotic cells and organisms with inducible protein expression systems using tetracycline-controlled transcriptional activation. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however protein translation is also disrupted in eukaryotic mitochondria impairing metabolism and leading to effects that can confound experimental results. Doxycycline is also used in "tet-on" (gene expression activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures. Doxycycline is more stable than tetracycline for this purpose. At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions.

title: Doxycycline


text:
Brian Warner

Brian Warner may refer to:

 * Brian Warner, birth name of Marilyn Manson, American rock musician
 * Brian Warner (cricketer), New Zealand cricketer
 * Brian Warner (astronomer), British South African astronomer
 * Brian D. Warner, American amateur astronomer and computer programmer

title: Brian Warner


text:
Amarum

In the mythology of the Quechua people of Peru, Amarum is a spirit in the shape of a water boa.

title: Amarum


text:
Rocky Colavito

Rocco Domenico "Rocky" Colavito Jr. (born August 10, 1933) is an American former professional baseball player, coach and television sports commentator. He played in Major League Baseball as an outfielder from 1955 to 1968, most prominently as a member of the Cleveland Indians where, he established himself as a fan favorite for his powerful hitting and his strong throwing arm.

A nine-time All-Star player, Colavito averaged 33 home runs per year for his first 11 seasons, exceeding 40 home runs three times and 100 runs batted in six times. He is the fifth player in the history of the American League (AL) to have eleven consecutive 20 home run seasons (1956–1966). In, he hit four consecutive home runs in one game and, was the AL home run champion. He was also the first outfielder in AL history to complete a season without making an error.

During his tenure in the major leagues, Colavito also played for the Detroit Tigers, Kansas City Athletics, Chicago White Sox, Los Angeles Dodgers, and New York Yankees. At the time of his retirement in 1968, Colavito ranked third among AL right-handed hitters for home runs (371) and eighth for AL games played as a right fielder (1,272).

After his playing career, Colavito worked as a television sports color commentator for WJW (TV) before returning to the playing field to serve as a coach with the Indians and the Kansas City Royals. In 2001, Colavito was voted one of the 100 greatest players in Cleveland Indians' history by a panel of veteran baseball writers, executives and historians. He was inducted into the Cleveland Guardians Hall of Fame in 2006.

Early years
Colavito was born and raised in The Bronx where he became a devoted New York Yankees fan, particularly of Joe DiMaggio. At the age of sixteen, he dropped out of Theodore Roosevelt High School after his sophomore year to play semi-professional baseball in hopes that it would lead to his dream of playing in Major League Baseball (MLB).

MLB rules called for a player to wait until his school class graduated before signing, and only a special appeal allowed him to go pro after a one-year wait. The Yankees expressed little interest in him, and the Philadelphia Athletics had to bow out due to financial problems. The Cleveland Indians did take interest in his strong throwing arm (Indians scout Mike McNally had watched him try out in Yankee Stadium) and signed him at age 17 as an undrafted amateur free agent on January 1, 1951, with two-thirds of his signing bonus deferred until he progressed in their system. In 1954, Colavito hit 38 home runs and accumulated 116 RBIs for the minor league baseball team, Indianapolis Indians.

Cleveland Indians
Colavito made his MLB debut on September 10, for the Cleveland Indians wearing number 38. In, he started the season playing in the Pacific Coast League, once showing off his throwing arm by hurling a ball over the center-field wall, 436 ft from home plate. In July, he returned to the Indians. He finished the season batting .276 with 21 home runs, and was tied for runner-up in the AL Rookie of the Year voting. In, he batted .252 with 25 home runs. In, Colavito, now wearing number 6, batted a career-high .303 with 41 home runs (one behind league leader Mickey Mantle) and 113 runs batted in. He led the AL that season in slugging with a .620 average (the highest by an Indians right-handed hitter until Albert Belle in ), and finished third in the MVP balloting. Colavito also pitched three hitless innings for Cleveland against the Detroit Tigers on August 13 that season.

In, Colavito hit 42 home runs and became the first Indians player to have two consecutive 40-HR seasons; he tied Harmon Killebrew for the AL lead that season (was one short of Al Rosen's club record) and was the AL leader in extra-base hits (66) and total bases (301). On June 10, at Baltimore Orioles' cavernous Memorial Stadium, he became the second player in AL history to hit four consecutive home runs in a nine-inning game; Lou Gehrig hit four in. In an interview in 2021, Colavito called the game the highlight of his career. He was selected for both of the All-Star Games held for the first time that season and homered in Game 2 (two All-Star games were held annually in 1959 through ). In the AL pennant race that year, the Indians finished second, five games behind the Chicago White Sox. This was the closest he would come to a title until 1967. He also finished fourth in the MVP vote. Colavito would hit 30-plus home runs for seven seasons, establishing himself as a consisent power hitter. He also was an excellent outfielder with a very strong arm despite being flat-footed.

Detroit Tigers
Colavito was easily the Cleveland fans' favorite, with his handsome appearance and approachability, always accommodating the hundreds of Indians autograph seekers after each game even if it took a few hours. On April 17,, Indians general manager Frank Lane unexpectedly traded him to the Detroit Tigers for Harvey Kuenn (the 1959 AL batting champion, having hit .353) just two days before the opening day of the season in Cleveland against the Tigers. The trade proved to be a good one for the Tigers but an unpopular trade for the Indians, whose fans lost their favorite player and best hitter. Kuenn had a minor injury early in the season, he hit .308 for the Indians, but was traded away at the end of the year. Lane, whose reputation as a wheeler-dealer earned him the moniker Frank "Trader" Lane in the sports press, further irritated fans by saying, "What's all the fuss about? All I did was trade hamburger for steak." Tigers general manager Bill DeWitt jokingly responded that he liked hamburger. Colavito (uniform #7) was placed in right field because of his strong throwing arm, moving Al Kaline to center field that season. Colavito hit .249 with 35 home runs and 87 RBI. In, Colavito hit .290 with a career-high 45 home runs, 140 RBI, and 129 runs scored. Detroit led the Major Leagues in scoring, and he placed eighth in the MVP race. Colavito was switched from right field to left field for the Tigers, and Kaline was reestablished in right field. Colavito was selected for both All-Star Games again and homered in Game 2. During one doubleheader that season, he hit 4 home runs, 3 in Game 2.

Tiger fans were happy to get Colavito in Detroit, but did not take to Colavito the same way as Indians fans had in Cleveland, preferring the more consistent Kuenn. Sportswriter Joe Falls, who viewed Colavito as a "self-ordained deity", began going after Colavito in the press and started a feature chronicling the runs he failed to drive in. The Detroit journalist kept a statistic on Colavito during his years playing for the Tigers. When Colavito stranded a runner, Falls would give him an "RNBI" (Run Not Batted In). This infuriated Colavito and created a tense relationship between the two of them for several years. In one game, Falls – acting as the official scorer – charged Colavito with a controversial error, and the "Rock" personally confronted him after the game. Another time when Colavito was in a batting slump and the Tigers fans started razzing him for it, he threw a ball he barely caught in left field over the right-field light tower and roof. On May 12, 1961, Colavito was ejected from a game with the Yankees in New York after climbing into the stands which was against MLB rules (though other Tigers players who followed Colavito into the stands were not ejected), to go after a drunken Yankee fan who had been scuffling with his older father there after the fan started harassing Colavito's wife. The Tigers played the game under protest, which they won 4–3. Colavito ($35,000 in 1961) drew the local fans' criticism by holding out for a higher 1962 salary ($54,000) than established team star Al Kaline ($39,000 to $49,000). In 1962, Colavito had 164 hits (Kaline 121), 37 home runs (Kaline 29), and 112 RBI (Kaline 94). He was selected for both All-Star Games for the third time and homered in Game 2. In 1963, Colavito hit .271, with 22 homers and 91 RBI.

Kansas City A's
Colavito was dealt along with Bob Anderson and $50,000 from the Tigers to the Kansas City Athletics for Jerry Lumpe, Dave Wickersham and Ed Rakow on November 18,. Wearing uniform #7, he spent only one season with Kansas City, earning a $50,000 salary as the highest-paid player on the A's. On September 11,, at 31, he became one of the youngest players to reach the 300-home-run mark (also was his 900th RBI), doing so against the Baltimore Orioles. Colavito hit .274, with 164 hits, 34 home runs, 31 doubles, and 102 RBI for the A's. He also was selected for the All-Star Game. The A's had finished in last place with a 57–105 record.

Return to Cleveland
In January, Colavito was brought back to Cleveland from Kansas City by Indians general manager Gabe Paul, by a three-team trade. Paul traded pitcher Tommy John (who would win 286 games after the trade and play until ), outfielder Tommie Agee ( AL Rookie of the Year and the New York Mets' top hitter in as they won their first pennant), and catcher John Romano, to the Chicago White Sox. The White Sox sent catcher Cam Carreon to Cleveland, and outfielder Mike Hershberger, center fielder Jim Landis, and pitcher Fred Talbot (February) to Kansas City.

During the home opener on April 21, with a crowd of 44,000, Colavito (uniform #21) hit a two-run homer. He hit .287 that season, and placed fifth in the MVP vote after leading the AL in RBI (108) and walks (93). He finished among the league's top five players in home runs (26), hits (170), and runs (92). He also was selected for his eighth All-Star Game. Colavito played in all of Cleveland's 162 games without committing an error (274 chances), but did not win one of the three AL Gold Glove Awards for an outfielder. On September 6, he got his 1,000th RBI. The Indians finished in 5th place with a 87–75 record.

In, Colavito hit .238 with 30 home runs and 72 RBI. He also was selected for his ninth and last All-Star Game. The Indians finished in 5th place with a 81–81 record. Colavito received a $55,000 and $57,000 salary from Cleveland, the highest given to an Indians' team player during those two years.

Chicago White Sox, LA Dodgers, and NY Yankees
In late July, Colavito (hitting .241 with 5 home runs and 21 RBI) was traded by the Indians to the Chicago White Sox, who finished three games out of first that season. In 60 games for the White Sox that season, Colavito managed to get 42 hits with 3 home runs and 29 RBI.

In March, he was purchased by the Los Angeles Dodgers from the White Sox. Colavito hit 3 home runs for the Dodgers in his National League debut, and batted .204 with 23 hits in 60 games. He was released by the Dodgers on July 11 that season.

On July 15, 1968, Colavito was signed as a free agent by the New York Yankees, the last team and season of his 14-year MLB playing career. During his first time up batting for the Yankees, he hit a three-run homer against the Senators. On August 25, Colavito (uniform #29), who was now 35 years old, became the last position player until Brent Mayne in to be credited as the winning pitcher in a game. He pitched $2 2/3$ scoreless innings as a reliever in the first game of a doubleheader against the league-leading Detroit Tigers. Not only did he face down Al Kaline and Willie Horton, he further vexed the Tigers by scoring the winning run for the Yanks in the eighth inning. He also homered in the second game. Colavito's pitching feat as a Yankee was not seen again in the AL until May 6, 2012, when Baltimore Oriole Chris Davis earned a win. Colavito got 20 hits including 5 home runs in 39 games played for the Yankees. He was released by the Yankees on September 30, 1968 and retired as a player.

Later career
Colavito was hired by the Cleveland Indians as a broadcaster on WJW-TV for the 1972 season. He was a first base coach for the Indians during the 1973 season, broadcaster during the 1975 season, hitting coach and broadcaster during the 1976 season, and first base coach during the 1977 and 1978 seasons. He was a hitting coach for the Kansas City Royals during the 1982 and 1983 seasons.

In 1982, Colavito and Kansas City Royals Manager Dick Howser, a former shortstop for the Indians, were involved in a traffic accident and struggle with police. Colavito and Howser were convicted of interfering with police and received 90-day jail sentences. Both appealed and served six months of probation.

Colavito was involved in the 1983 pine tar game and was ejected for arguing the umpires' decision to negate George Brett's home run and call him out, which would have given the Yankees the win; the decision was later overturned, the game was resumed a month later with the Royals in the lead as the result of Brett's home run, and the Royals won the game.

Personal life
Colavito has been married since 1954. On August 11, 2015, he had to have his right leg amputated below the knee due to problems with Type 2 diabetes, of which he had suffered for a number of years.

MLB stats
Batting stats: Pitching stats: Fielding stats:

MLB achievements
Notable achievements: Other achievements:
 * 6-time AL All-Star (1959, 1961, 1962, 1964, 1965, 1966)
 * AL Slugging Percentage Leader (1958)
 * 2-time AL Total Bases Leader (1959, 1962)
 * AL Home Runs Leader (1959)
 * AL RBI Leader (1965)
 * AL Base on Ball Leader (1965)
 * 20-Home Run Seasons: 11 (1956–1966)
 * 30-Home Run Seasons: 7 (1956–1962, 1964, 1966)
 * 40-Home Run Seasons: 3 (1958, 1959, 1961)
 * 100 RBI Seasons: 6 (1958, 1959, 1961, 1962, 1964, 1965)
 * 100 Runs Scored Seasons: 1 (1961)
 * 9 All-Star Games (1959-2, 1961–2, 1962–2, 1964, 1965, 1966)
 * ML Fielding Percentage Leader as Right Fielder (1965)
 * ML Fielding Percentage Leader as Outfielder (1965)
 * Four consecutive home runs in one game (1959)
 * Four home runs in one game (1959)

Legacy
Colavito was one of the most popular power hitters and outfielders of his time with one of the best throwing arms in baseball.

In, Colavito was voted the most memorable personality in Indians history.

In, Colavito received a huge ovation at the introduction of the Indians' All-Century team.

On July 29, 2006, Colavito, along with Ray Chapman, Addie Joss, Sam McDowell, Al Rosen, Herb Score and manager Al López, were all inducted into the Cleveland Indians Hall of Fame.

On August 10, 2021, his 88th birthday, a statue of Colavito was unveiled at Tony Brush Park in Cleveland's Little Italy. Colavito was in attendance for the ceremony.

The Curse of Rocky Colavito
In 1994, Terry Pluto, who covered the Cleveland Indians for The Plain Dealer in the 1980s and became the top sports columnist for the Akron Beacon Journal (but returned to The Plain Dealer in 2007), published The Curse of Rocky Colavito, a book that tried to explain why the Indians had not come within even 11 games of first place since 1959. Pluto's explanation was that the trade of Colavito by the Indians in 1960 sent the team on a path to mediocrity that lasted more than three decades. He also suggested that the trade in 1965 to bring Colavito back to the Indians was just as bad as the one that had sent him away.

Pluto wrote a sequel, Burying the Curse, in 1995, after the Cleveland Indians won their first American League Championship in 41 years that season. Cleveland lost the World Series 4–2 to the Atlanta Braves. In, the Indians won the AL pennant again, but lost the World Series 4–3 to the Florida Marlins after needing just two more outs in Game 7 to win. In 1999, Pluto wrote the book Our Tribe, a history of the Cleveland Indians. Pluto insists in the book, that the curse is still in effect.

The Indians' won the American League Championship again 19 years later, in 2016. Cleveland lost the World Series to the Chicago Cubs 4–3; Cleveland's last World Series title was in 1948, when they defeated the Boston Braves.

title: Rocky Colavito


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Wikipedia:Articles for deletion/RoyalNavy21

Useless, irrelevant stub - but that can change, so that's not the point. Point is, do we need these pages? Why not keep this to Royal Navy, where people are likely to actually find it? -- Jao 13:54, 17 May 2004 (UTC)
 * Current content is irrelevant to the title, and not especially useful. If there were good information here, however, it would be findable because it was linked from an appropriate location in the Royal Navy article, or possibly in History of the Royal Navy, which doesn't yet exist but really ought to.  Isomorphic 15:29, 17 May 2004 (UTC)
 * Merge and redirect to Royal Navy, which already has a good section on its history. I think this content is a minor but good contribution and should be merged. So, move this article to History of the Royal Navy first, so the eventual result is that the history of this page is preserved under that name, and The Royal Navy in the 21st Century can then be listed in redirects for deletion . Certainly don't delete, despite being by an anon this article is part of a lot of good work by a newcomer on various Royal Navy articles. Andrewa 16:47, 17 May 2004 (UTC)
 * I've merged and redirected. Info about "the Royal Navy in the 21st Century" (that is to say, now) is exactly what I'd expect to see in the main article.  The entire history of the Royal Navy can be moved out to its own article if/when necessary but I don't think it's necessary yet. Because it is now a harmless redirect, I do not recommend deletion .(This also preserves the anon contributions.) Rossami 17:22, 17 May 2004 (UTC)
 * Keep as redirect (change of vote, sort of). Certainly a lot simpler than what I proposed. Andrewa 20:56, 17 May 2004 (UTC)
 * Original poster accepts this too. I don't see the use of this redirect, but there's no harm, either. -- Jao 08:13, 18 May 2004 (UTC)
 * Sounds good. Keep redirect.Beelzebubs 20:39, 17 May 2004 (UTC)
 * Keep. It's a good article -- Cabalamat 19:13, 20 May 2004 (UTC)


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User:APEuroHistory9

AP European History sucks!!!

title: User:APEuroHistory9


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String sextet

In classical music, a string sextet is a composition written for six string instruments, or a group of six musicians who perform such a composition. Most string sextets have been written for an ensemble consisting of two violins, two violas, and two cellos.

Notable string sextets
Among the earliest works in this form are the nine string sextets Op. 23 by Luigi Boccherini, written in 1776. Other notable string sextets include the String Sextets Op. 18 and 36 by Brahms, Dvořák's Op. 48, Tchaikovsky Souvenir de Florence, Op. 70, Schoenberg's Verklärte Nacht, Op. 4, Erich Wolfgang Korngold Op. 10, Erwin Schulhoff's String Sextet of 1924, and Charles Wuorinen's String Sextet of 1989.

Less usual combinations
More unusual combinations for a string sextet:

 * three violins, viola and two cellos: Ferdinand David (1810–1873), op. 38, Gaetano Brunetti (1744–1798), op. 1, Eugene Goossens (1893–1962), op. 37
 * three violins, two violas and cello: Jan Brandts Buys (1868–1933), op. 40
 * two violins, two violas, cello, double bass: Ignaz Pleyel (1757–1831) B.271, and others
 * two violins, viola, two cellos, double bass: including works by Auguste Franchomme (1808–1884) and Ignacy Feliks Dobrzyński (1807–1867)

Selected list of string sextets

 * Luigi Boccherini (1743–1805) String Sextets, Op. 23 (1776)
 * Alexander Borodin (1833–1887) String Sextet in D minor (2 movements) (1860/61)
 * Hakon Børresen (1876–1954) Sextet in G major, Op. 5 (1901)
 * Johannes Brahms (1833–1897)
 * String Sextet No. 1 in B-flat major, Op. 18 (33')
 * String Sextet No. 2 in G major, Op. 36 (33')
 * Frank Bridge (1879–1941) String Sextet (1906–1912) (27')
 * Karl Davydov (1838–1889) Sextet, Op. 35 (1880) dedicated to Leopold Auer
 * Ignacy Feliks Dobrzyński (1807–67) Sextet in E-flat major, Op.39 (1845) (for 2 violins, viola, 2 cellos & bass)
 * Ernő Dohnányi (1877–1960) String Sextet in B-flat major (1893, revised 1898)  (27')
 * Antonín Dvořák (1841–1904) String Sextet in A major, Op. 48, B. 80 (31')
 * Iván Erőd (1936–2019)
 * Serenade for string sextet, Op. 45 (1983)
 * 2nd String Sextet, Op. 68 (1996)
 * Eduard Franck (1817–1893)
 * String Sextet No. 1 in E-flat, Op. 41 (1882)
 * String Sextet No. 2 in D major, Op. 50 (1894)
 * Niels Gade (1871–1890) Sextet in E-flat major, Op. 44 (1865)
 * Louis Glass (1864–1936) Sextet in G major, Op. 15 (1893)
 * Reinhold Glière (1875–1956)
 * Sextet No. 1 in C minor (1898)
 * String Sextet No. 2 in B minor, Op. 7 (1904)
 * String Sextet No. 3 in C major, Op. 11 (1904)
 * Heinrich Hofmann (1842–1902) Sextet Op. 25 (1874)
 * Joseph Holbrooke (1878–1958) Sextet in D, Op. 43 (1924)
 * Vincent d'Indy (1851–1931) String Sextet in B-flat major, Op. 92 (1927)
 * Mauricio Kagel (1931–2008) String Sextet (1953, rev. 1957)
 * Hans von Koessler (1853–1926) Sextet in F minor (1902)
 * Erich Wolfgang Korngold (1897–1957) String Sextet in D major, Op. 10 (1917) (33')
 * Arnold Krug (1849–1904) Sextet in D major, Op. 68
 * Max Lewandowsky (1874–1906) Sextet, Op. 5 (1904)
 * Bohuslav Martinů (1890–1959) String Sextet, H. 224  Paris, 1932  (15-16')
 * Mihály Mosonyi (1815–1870) String Sextet in C minor (32')
 * Per August Ölander (1824–1886) String Sextet  (1876?)
 * Walter Piston (1894–1976) String Sextet (1964) (18')
 * Joachim Raff (1822–1882) Sextet in G minor, Op. 178  (1872)
 * Max Reger (1873–1916) Sextet in F major, Op. 118 (1910)
 * Friedhelm Rentzsch (born 1955) String Sextet (1981)  (15')
 * Nikolai Rimsky-Korsakov (1844–1908) String Sextet in A major (30')
 * Paul Rosenbloom (born 1952) String Sextet (1978) (30')
 * Anton Rubinstein (1829–1894) Sextet in D major, Op. 97
 * Peter Schickele (born 1935) String Sextet (1990) (26')
 * Arnold Schoenberg (1874–1951) Verklärte Nacht (Transfigured Night), Op. 4 (1899) (29')
 * Erwin Schulhoff (1894–1942) String Sextet (1924) (21')
 * Salvatore Sciarrino (born 1947) Sestetto (2003) (22')
 * Louis Spohr (1784–1859) String Sextet in C major, Op. 140 (1848) (24')
 * Richard Strauss (1864–1949) from the Opera Capriccio, Op. 85 (1942) (10')
 * Pyotr Ilyich Tchaikovsky (1840–1893) Souvenir de Florence, Op. 70  (35')
 * Graham Waterhouse (born 1962) String Sextet op. 1 (1979–2013)
 * Nicolai von Wilm (1834–1911) Sextet in B minor, Op. 27 (1898)
 * Ermanno Wolf-Ferrari (1876–1948) Sextet in C minor (1894-5)
 * Charles Wuorinen (1938–2020) String Sextet (1989)

title: String sextet


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Ilomba

Ilomba is a sea snake with destructive powers in the mythology of the Lozi people of Zambia. It is created by a witch doctor. It is made with their finger nails and blood from their forehead, back, and chest. They mix it in a pan with herbs that were considered to have a magical force. It is usually fed with eggs and porridge when it is young because its fangs are not fully developed. It takes on the identity of the person that owns it. The owner will command it to kill a person. The victim will see the witch doctor's face in place of the Ilomba's, but the other people will view it as a normal snake. It bites into its prey then consumes its soul. If it is killed, the owner feels the pain, and then dies. If the owner dies, it dies. If the witch doctor stops supplying food to it, it will turn on its master and consume them. The only way it can be destroyed is through the witch doctor. When the witch doctor does kill it, they will be constantly haunted by the souls that the Ilomba consumed.

title: Ilomba