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Pernicious anemia



 
 
Pernicious anemia (also known as Biermer's anemia, Addison's anemia, or Addison-Biermer anemia) is a form of megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
 due to vitamin B12 deficiency
Avitaminosis

Avitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin....
, caused by impaired absorption of vitamin B-12 due to the absence of intrinsic factor
Intrinsic factor

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the terminal ileum....
 in the setting of atrophic gastritis
Atrophic gastritis

Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues....
, and more specifically of loss of gastric
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
 parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s.

While the term 'pernicious anemia' is sometimes also incorrectly used to indicate megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
 due to any cause of vitamin B12 deficiency
Vitamin B12 deficiency

B12 deficiency is a reduction in vitamin B12 from inadequate dietary intake or impaired absorption. The condition is commonly asymptomatic, but can also present as anemia characterized by enlarged blood corpuscles, so-called megaloblastic anemia....
, its proper usage refers to that caused by atrophic gastritis and parietal cell loss only.






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Pernicious anemia (also known as Biermer's anemia, Addison's anemia, or Addison-Biermer anemia) is a form of megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
 due to vitamin B12 deficiency
Avitaminosis

Avitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin....
, caused by impaired absorption of vitamin B-12 due to the absence of intrinsic factor
Intrinsic factor

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the terminal ileum....
 in the setting of atrophic gastritis
Atrophic gastritis

Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues....
, and more specifically of loss of gastric
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
 parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s.

While the term 'pernicious anemia' is sometimes also incorrectly used to indicate megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
 due to any cause of vitamin B12 deficiency
Vitamin B12 deficiency

B12 deficiency is a reduction in vitamin B12 from inadequate dietary intake or impaired absorption. The condition is commonly asymptomatic, but can also present as anemia characterized by enlarged blood corpuscles, so-called megaloblastic anemia....
, its proper usage refers to that caused by atrophic gastritis and parietal cell loss only. It is the most common cause of adult vitamin B-12 deficiency.

Mechanisms and manifestations


Pathophysiology

Vitamin B-12 cannot be produced by the human body, and must therefore be obtained from diet. Normally, dietary vitamin B-12 can only be absorbed by the ileum
Ileum

The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum....
 when it is bound by the intrinsic factor
Intrinsic factor

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the terminal ileum....
 produced by parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s of the gastric
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
 mucosa. In pernicious anemia, this process is impaired because of loss of parietal cells, resulting in insufficient absorption of the vitamin, which over a prolonged period of time ultimately leads to vitamin B-12 deficiency and thus megaloblastic anemia. This anemia is a result of the body's inability to produce DNA
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
 in sufficient quantities for blood cell synthesis, due to interruption of a biochemical pathway that is dependent on vitamin B-12 and/or folic acid
Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
 as cofactors, which synthesizes thymine
Thymine

Thymine is one of the four bases in the nucleic acid of DNA that make up the letters GCAT. The others are adenine, guanine, and cytosine. Thymine always pairs with adenine....
, a DNA component.

Presentation

The presentation of pernicious anemia resembles that of any other form of anemia, but is often accompanied by the manifestations of vitamin B12 deficiency (notably neurological abnormalities such as peripheral neuropathy
Peripheral neuropathy

Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the Adverse effect of systemic illness....
), as well as by other manifestations of autoimmune atrophic gastritis.

Causes

Most commonly (in temperate climates), the cause for impaired binding of vitamin B12 by intrinsic factor is autoimmune atrophic gastritis
Atrophic gastritis

Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues....
, in which autoantibodies
Autoantibody

An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins.It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"....
 are directed against parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s (resulting in their loss) as well as against the intrinsic factor
Intrinsic factor

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the terminal ileum....
 itself (rendering it unable to bind vitamin B-12).

Less frequently, loss of parietal cells may simply be part of a widespread atrophic gastritis of non-autoimmune origin, such as that frequently occurring in elderly people affected with long-standing chronic gastritis
Gastritis

Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen....
 of any cause (including Helicobacter pylori
Helicobacter pylori

Helicobacter pylori is a Gram-negative, microaerophile bacterium that inhabits various areas of the stomach and duodenum. It causes a chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric peptic ulcers and stomach cancer bacteria....
 infection).

Note that forms of vitamin B-12 deficiency other than pernicious anemia must be considered in the differential diagnosis
Differential diagnosis

A differential diagnosis is a systematic method used to identify unknowns. This method, essentially a process of elimination, is used by taxonomy to identify living organisms, and by physicians and other qualified healthcare professionals to diagnosis the specific disease in a patient....
 of megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
. For example, a B-12 deficient state which causes megaloblastic anemia and which may be mistaken for classical pernicious anemia, may be caused by infection with the tapeworm Diphyllobothrium latum, possibly due to the parasite's competition for vitamin B-12, .

Symptoms


The symptoms of PA vary from patient to patient. Some patients might experience all of the symptoms listed below, whilst others may experience just one or two. Some patients are asymptomatic and experience no symptoms and yet can still PA. Similarly, the degree to which the symptoms are experienced will depend on a number of factors including how soon treatment was started.

Common physical symptoms


Fatigue None of the above words adequately or accurately explains the feeling that is experienced by the majority of patients with Pernicious Anaemia. The physical tiredness is also often accompanied with mental fatigue and apathy. The most common description recognised by patients is that of “The Strange Tiredness” which is understood by most sufferers as being an adequate description of the experience. Sometimes the Strange Tiredness lasts for hours, sometimes days and often it’s the case that it never really fully goes away. It is also usual for the Strange Tiredness to be worse on some days than on others and it can be debilitating for the long-term sufferer. Patients and their families and friends often have to make lifestyle adjustments to be able to manage this experience. Many patients retire to their beds in an effort to manage their condition and the saying “at least ten, usually twelve and sometimes more” is sometimes used by sufferers to describe how many hours sleep they need. Feeling tired or exhausted can be a very negative experience as anyone who has played sport can tell you. But this Strange Tiredness is not a pleasant experience. It is an insidious, creeping, overpowering feeling that seems to sap any strength that the patient might have. It doesn’t often leave the sufferer being unable to do normal and everyday tasks but rather makes such tasks (however trivial) a real trial. Sufferers often cope with everyday work and domestic tasks, but most struggle to do so. Many patients wake up tired in the morning, despite sleeping heavily for over the usual 8 hours the patient. A great many patients report needing more than 10 hours each night.

Shortness of breath This is one of the most misunderstood of all the symptoms. There are some sufferers who begin to breathe heavily when performing any physical activity such as walking up stairs, general household cleaning, lifting and brisk walking, but only very rarely is there any gasping for air. However, it is the need to take deep breaths when not performing any activity that causes the most concern. Sufferers often refer to this need to take in ‘lumps’ of air as ‘The Sighs.’ Often it may seem that the patient is struggling to breath, but he or she will simply be trying to satisfy the need to take in a deep breath. This can often be accompanied by the need to yawn, sometimes almost continually. One of the strangest aspects of The Sighs is that they don’t occur every day. Patients often talk of good & bad days. On good days the patient might not feel the need to ‘sigh’. On bad days he or she might need to ‘sigh’ for most of the day or for just a short period.

Swollen tongue (Glossitis
Glossitis

Glossitis is inflammation or infection of the tongue. It causes the tongue to swell and change color. Finger-like projections on the surface of the tongue may be lost, causing the tongue to appear smooth....
) This is often quoted as being one of the most common symptoms of P.A. However, only a small percentage of sufferers of Pernicious Anaemia experienced a swollen, smooth and ‘beefy’ red tongue. Perhaps the figure is as low as 10%. Those who do have a swollen tongue often complain that their tongue bleeds and becomes tender.

Feeling bloated or full This is often accompanied by a physical swelling of the stomach. The patient will feel ‘full’.

Brittle, easily damaged nails The nails on both hands and feet become brittle and split or break very easily. Many patients never have to trim or cut their nails as they break off whenever they become anything other than short.

Pins and needles sensation (Paraesthesia/Parasthesia) This can be the first sign of damage to the peripheral nerves. The pins & needles can be experienced anywhere on the body but it mainly affects the tips of fingers and feet. Many patients report that these pins & needles disappear completely after they receive their prescribed treatment. Rather strangely in some cases the pins and needles disappear within hours of the first injection of Hydroxocobalamin being administered.

Sock and glove feeling. This refers to a numb sensation in the patient’s fingers and feet – it feels as if you are wearing socks and gloves. Again this can be seen as damage to the peripheral nerves but patients often report that this sensation disappears once treatment is started.

Unaccountable sudden Diarrhea
Diarrhea

In medicine, diarrhea, also spelled diarrhoea , is characterized by frequent loose or liquid bowel movements. The spelling of "diarrhea" is an appropriation of the Greek "diarrhoia" meaning "a flowing through." ....
. Again this is a often experienced but not often talked about and can be attributed to Irritable Bowel Syndrome—however this is not always the case.

Less common symptoms


  • Unsteadiness or unusual gait
    Gait

    Gait is the pattern of movement of the limbs of terrestrial animals during locomotion. Most animals use a variety of gaits, selecting gait based on speed, terrain, the need to maneuver, and energetic efficiency....
     due to central nervous system damage (demyelination).
  • Vertigo
    Vertigo (medical)

    Vertigo is a specific type of dizziness, a major symptom of a balance disorder. It is the sensation of spinning or swaying while the body is actually stationary with respect to the surroundings....
    .
  • Burning feet/legs. This occurs mainly in middle-age and is usually worst at night. It is directly linked to B12 deficiency and usually disappears once treatment is started. It is known to doctors as Brierson-Goplan syndrome.


Common mental symptoms

As well as physical symptoms, sufferers of P.A. also experience changes to their mental ability. These cognitive symptoms are often more difficult to explain and deal with than the physical symptoms. It seems to be the case that these mental challenges are often not recognised or acknowledged by some medical professionals. As with the physical symptoms, the degree and effect of these symptoms will vary between different patients.

Brain fog
Brain fog

Cognitive dysfunction is defined as unusually poor mental function, associated with confusion, forgetfulness and difficulty concentrating. A number of medical or psychiatric conditions and treatments can cause such symptoms, including Heavy metal poisoning , menopause and sleep disorders ....
This is by far the most common complaint by sufferers of P.A. Patients find it difficult to define exactly what they experience on a ‘foggy’, but there is a general feeling of lack of focus and a lack of clarity in everything they experience. It’s as if the patient is experiencing being in a thick fog, with all of the senses failing to respond as quickly as they usually do.

The degree to which this occurs is directly proportional to whether the patient is experiencing a good or bad day. On a bad day it is possible that the patient will forget the names of even their closest relatives, be unable to recall even the most common proper nouns, repeatedly ask the same question, forget a conversation from even the shortest time before, make mistakes in their work — even the most fundamental mistakes and feel ‘not with it’. The patient will often seek peace and tranquillity in order to give full concentration to the task he or she is dealing with. The most common way in which the patient can explain what it feels like to be in a fog can be summarised by the following statements:

  • “I just want the world to go away”.
  • “I just want to be left alone”.
  • “I don’t want to be forced into conversation”.


Patients also state that leisure activities such as reading, watching television or going to the cinema can be enjoyed during a ’fog’, but the next day the chapter of the book that was read, or the outcome of a t.v. programme and the plot of a film will be forgotten. The chapter of the book would have to be re-read and the television programme or film would have to be seen again. ‘Fogs’ can last a few hours, a day, or a few days. Patients are aware that they are experiencing a ‘fog’ but are unable to do anything about it. It’s simply a case of ‘riding it out’ Most patients wake up either the next day or in a few days time and experience a clarity and focus to their thinking which had been absent during the fog.

Irritability, impatience and mood swings This is another very common condition amongst sufferers of Pernicious Anaemia and is probably has the greatest impact on personal relationships.

Diagnosis

The insiduous nature of the disease, and the fact that there is no single definitive test for Pernicious Anaemia can often mean that a diagnosis is late. The Schilling Test is no longer available, and the other main diagnostic signpost of low levels of serum B12 cannot be relied upon as sufferers can have high levels of serum B12 and still have Pernicious Anaemia A diagnosis of pernicious anemia first requires demonstration of megaloblastic anemia
Megaloblastic anemia

Megaloblastic anemia is an anemia which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid....
 (through a full blood count) which evaluates the mean corpuscular volume
Mean corpuscular volume

The mean corpuscular volume, or MCV, is a measure of the average red blood cell volume that is reported as part of a standard complete blood count....
 (MCV), as well the mean corpuscular hemoglobin concentration
Mean corpuscular hemoglobin concentration

The mean corpuscular hemoglobin concentration, or MCHC, is a measure of the concentration of hemoglobin in a given volume of packed red blood cell....
 (MCHC). Pernicious anemia is identified with a high MCV and a normal MCHC (that is, it is a macrocytic
Macrocytic

Macrocytic can refer to:* macrocytosis* macrocytic anemia...
, normochromic
Normochromic

Normochromic is a form of anemia in which the concentration of haemoglobin in the red blood cells is within the standard range....
 anemia). . Ovalocytes are also typically seen on the blood smear, and a pathognomonic
Pathognomonic

Pathognomonic is an adjective of Greek origin , often used in medicine, which means diagnosis for a particular disease. A pathognomonic Medical sign is a particular sign whose presence means, beyond any doubt, that a particular disease is present....
 feature of megaloblastic anemias (which include pernicious anemia and others) is hypersegmented neutrophils.

Pernicious anemia can also be diagnosed by evaluating its direct cause, vitamin B-12 deficiency (by measuring B-12 levels in serum). A Schilling test
Schilling test

The Schilling's test is a medical investigation used in patients with vitamin B12 deficiency. The purpose of the test is to determine if the patient has pernicious anemia....
 can then be used to distinguish pernicious anemia from other causes of vitamin B-12 deficiency (notably malabsorption
Malabsorption

Malabsorption is a state arising from abnormality in digestion or absorption of Nutrient across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality....
).

A diagnosis of atrophic gastritis
Atrophic gastritis

Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues....
 should be confirmed by gastroscopy with biopsies
Biopsy

A biopsy is a medical test involving the removal of Cell_s or Biological tissues for examination. It is the removal of tissue from a living subject to determine the presence or extent of a disease....
. Approximately 90% of individuals with pernicious anemia have antibodies for parietal cells; however only 50% of all individuals in the general population with these antibodies have pernicious anemia.

Treatment

The treatment of Pernicious Anaemia varies from country to country and from area to area. There is, as yet, no cure for Pernicious Anaemia and consequently treatment centres on replacing Vitamin B12. This is done in a variety of ways. Cobalamin (B12) is usually injected into the patient's muscle (IntraMuscular or I.M.) using Cyanocobalamin (The United States, Canada and most European countries) or Hydroxocobalamin (Australia and the U.K.). The injections will be for life and will be given every month in some countries and every three months in other countries. The single most common cause of complaint by members of the Pernicious Anaemia Society is that patients needs vary and some patients need more frequent injections than others .

In some countries the Cobalamin preparation is available over the counter from chemists, while in other countries it is only available via doctors prescription.

Patients who are needlephobic, or patients who are unable to receive injections for another reason can be prescribed Cyanocobalmin tablets in very high doses which means that some of the B12 is absorbed further on in the digestive process than where absorption usually takes place. The efficacy of using tablets to treat Pernicious Anaemia is unknown as only scant research into this has taken place. Some patients are treated by Methylcobalamin Sub-Lingual tablets that are placed under the tongue where some B12 is absorbed via the membrane under the tongue.

Some doctors and medical professionals believe that Sub Cutaneous injections are more effective than I.M. injections. There are other methods of administering B12 including behind the ear patches and nasal sprays but again the efficacy of these methods of treatment has not been subjected to any serious scientific investigation.

Being a manifestation of vitamin B-12 deficiency, pernicious anemia is treated by administering vitamin B-12 supplements. Oral tablets are sometimes used, though if this approach is used, much higher doses are given than normally required in order to overcome the impaired absorption that characterizes pernicious anemia.

If oral tablets are not desired, vitamin B-12 can also be administered via injection
Injection (medicine)

An injection is an route of administration of putting liquid into the body, usually with a hollow hypodermic needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body....
, which is usually given once a month, thus bypassing any intrinsic factor problems and the need for gastrointestinal absorption altogether. Often the patient can learn to do this at home with the same syringes and needles used for insulin treatment of diabetes.

History

Dr. Addison first described the disease, from which it acquired the common name of Addison's Anemia. In 1907 Richard Clarke Cabot
Richard Clarke Cabot

Richard Clarke Cabot was an American doctor who worked in the Massachusetts General Hospital in the late 18th and early 19th centuries. He is widely credited with creating one of the first positions of professional Social workers in the world, given to Garnet Pelton.....
 reported on a series of 1200 patients with PA. Their average survival was between one and three years. Dr. William Bosworth Castle performed an experiment whereby he ingested raw hamburger meat and regurgitated it after an hour and subsequently fed it to a group of ten patients. A control group were fed un-treated raw hamburger meat. The former group showed a disease response whereas the latter group did not. This was not a sustainable practice but it demonstrated the existence of an 'intrinsic factor' from gastric juice.

Pernicious anemia was a fatal disease before about the year 1920, when Whipple suggested raw liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 as a treatment. After verification of Whipple's results in 1926, pernicious anemia victims ate or drank at least 1/2 a pound of raw liver, or drank raw liver juice every day. This continued for several years until a concentrate of liver juice became available after 1928.

The first workable treatment for pernicious anemia began with the work of George Whipple
George Whipple

George Hoyt Whipple was an American physician, biomedical researcher, and medical school educator and administrator. Whipple shared the Nobel Prize in Physiology or Medicine in 1934 with George Richards Minot and William Parry Murphy "for their discoveries concerning liver therapy in cases of anemia."...
 who made the discovery in the course of experiments in which he bled dogs to make them anemic, then fed them various foods to see which would make them recover most rapidly (Whipple was looking for treatments for anemia from bleeding, not pernicious anemia). Whipple discovered that ingesting large amounts of liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 seemed to cure anemia from blood loss, and tried liver ingestion as a treatment for pernicious anemia, reporting improvement there also, in a paper in 1920. George Minot and William Murphy
William Murphy

William Murphy may refer to:* William P. Murphy , American physician and Nobel laureate* William P. Murphy Jr. , his son, American scientist and inventor in the field of medical instrumentation...
 then set about to partly isolate the curative property in liver and showed that it was contained in raw liver juice (in the process also showing that ironically it was the iron in liver tissue, not the soluble factor in liver juice, which cured the anemia from bleeding in dogs; thus the discovery of the liver juice factor as a treatment for pernicious anemia, had been by coincidence). For the discovery of the cure of a previously fatal disease of unknown etiology
Etiology

Etiology is the study of Causality. The word is derived from the Ancient Greek , aitiologia, "giving a reason for" .The word is most commonly used in medical and philosophical theories, where it is used to refer to the study of why things occur, or even the reasons behind the way that things act, and is used in philosophy, physics, psy...
 the three men shared the 1934 Nobel Prize in Medicine
Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institutet. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Nobel Prize in Physics, Nobel Prize in Chemistry, Nobel Prize in Literature, Nobel Peace Prize, and Physiology or Medic...
.

In 1928 chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural food (liver). The extract could even be injected into muscle, which meant that patients no longer needed to eat large amounts of liver or juice. This reduced the cost of treatment considerably.

The active ingredient in liver was unknown until 1948, when it was isolated by two chemists, Karl A. Folkers of the United States and Alexander R. Todd of Great Britain. The substance was a cobalamin
Cobalamin

Cobalamin may refer to several substances depending on the upper axial ligand of the cobalt ion. These are:*Cyanocobalamin , which is not found in nature....
, which the discoverers named vitamin B-12. The new vitamin in liver juice was eventually completely purified and characterized in the 1950s, and other methods of producing it from bacteria were developed. It could be injected into muscle with even less irritation, making it possible to treat pernicious anemia with even more ease. Pernicious anemia was eventually treated with either vitamin B-12 injections, or else large oral doses of vitamin B-12, typically between 1 and 4 mg (1000 to 4000 mcg) daily.

Notable sufferers

  • Inez Milholland
    Inez Milholland

    Inez Milholland Boissevain was a suffragist, labor lawyer, World War I correspondent, and public speaker who greatly influenced the women's movement in America....
    , American Suffragette
    Suffragette

    File:British suffragette.jpgSuffragette is a term originally coined by the Daily Mail newspaper as a derogatory label for the more Political radicalism and militant members of the late-19th and early-20th century movement for women's suffrage Women's suffrage in the United Kingdom, in particular members of the Women's Social and Politica...
  • Alexander Graham Bell
    Alexander Graham Bell

    Alexander Graham Bell was an eminent scientist, Innovation and innovator who is credited with inventing the first practical telephone.Bell's father, grandfather, and brother had all been associated with work on elocution and speech, and both his mother and wife were deaf, profoundly influencing Bell's life's work....
    , Scottish scientist and inventor who immigrated to Canada
  • Sir Laurence Gomme
    Laurence Gomme

    Sir Laurence Gomme, Society of Antiquaries of London#Membership was a public servant and leading British folklorist. He helped found both the Victoria County History and the Folklore Society....
     public servant and folklorist
  • Annie Oakley
    Annie Oakley

    Annie Oakley was an United States Marksman and exhibition shooting. Oakley's amazing talent and timely rise to fame led to a starring role in Buffalo Bill show, which propelled her to become the first American female superstar....
    .
  • Norman Warne, editor/publisher and fiancé of Beatrix Potter
    Beatrix Potter

    Helen Beatrix Potter was an English author, illustrator, mycology and Conservation movement who was best known for her many best-selling Children's literature that featured animal characters, such as Peter Rabbit....
    .
  • Yoon Eun Hye
    Yoon Eun Hye

    Yoon, Eun-Hye is a South Korean actress, singer, and model. She debuted as a member of the popular girl group Baby V.O.X, staying with the group from 1999 - 2005....
    , a South Korean actress
  • Betsie ten Boom
    Betsie ten Boom

    Elisabeth ten Boom was one of the leading characters in The Hiding Place , a book written by her sister Corrie ten Boom about the family's experiences during World War II ....
    , sister to Corrie ten Boom
    Corrie ten Boom

    Cornelia Johanna Arnolda ten Boom, generally known as Corrie ten Boom, was a Netherlands, Christian Holocaust survivor who helped many Jews escape the Nazism during World War II....
    , victim of the Holocaust, and in the book, The Hiding Place
    The Hiding Place

    The Hiding Place is the title of:*The Hiding Place , a 1971 book by Corrie ten Boom*The Hiding Place , a 1975 film based on the book by ten Boom...
  • David Hilbert
    David Hilbert

    David Hilbert was a Germany mathematician, recognized as one of the most influential and universal mathematicians of the 19th and early 20th centuries....
    , German mathematician
  • Sam Hughes
    Sam Hughes

    Sir Samuel Hughes, Order of the Bath, Queen's Privy Council for Canada was the Canada Minister of Militia and Defence during World War I. He was notable for being the last Liberal-Conservative cabinet minister, until he was dismissed from his cabinet post....
    , Canadian Minister of Militia and Defence
  • Henry Sweet
    Henry Sweet

    Henry Sweet was an English philology, phonetic and grammarian.As a philologist, he specialized in the Germanic languages, particularly Old English and Old Norse....
    , English linguist and phoneticist
    Phonetics

    Phonetics is a branch of linguistics that comprises the study of the sounds of human speech. It is concerned with the physical properties of speech sounds , and the processes of their physiological production, auditory reception, and neurophysiological perception....
  • Sir Stafford Cripps - British Politician and Chancellor of the Exchequer in the post-World War 2 Labour government.
  • Suzanne Lenglen
    Suzanne Lenglen

    Suzanne Rachel Flore Lenglen was a French tennis player who won 31 Grand Slam titles between 1914 and 1926. A flamboyant, trendsetting athlete, she was the first female tennis celebrity and one of the first international female sport stars, named La Divine by the French press....
     - French tennis player


External links

  • , a UK-based charitable organisation