Vein

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Vein
Venous system en.svg
The main veins in the human body
Vein (retouched).svg
Structure of a vein, which consists of three main layers. The outer layer is connective tissue, called tunica adventitia or tunica externa; a middle layer of smooth muscle called the tunica media, and the inner layer lined with endothelial cells called the tunica intima.
Details
System Circulatory system
Identifiers
Latin vena
MeSH D014680
TA A12.0.00.030
A12.3.00.001
FMA 50723
Anatomical terminology

Veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart. In contrast to veins, arteries carry blood away from the heart.

Contents

Veins are less muscular than arteries and are often closer to the skin. There are valves in most veins to prevent backflow.

Structure

Veins are present throughout the body as tubes that carry blood back to the heart. Veins are classified in a number of ways, including superficial vs. deep, pulmonary vs. systemic, and large vs. small.

Most veins are equipped with one-way valves, similar to a Duckbill valve, to prevent blood flowing in the reverse direction.

Veins are translucent, so the color a vein appears from an organism's exterior is determined in large part by the color of venous blood, which is usually dark red as a result of its low oxygen content. Veins appear blue because the subcutaneous fat absorbs low-frequency light, permitting only the highly energetic blue wavelengths to penetrate through to the dark vein and reflect back to the viewer. The colour of a vein can be affected by the characteristics of a person's skin, how much oxygen is being carried in the blood, and how big and deep the vessels are. [2] When a vein is drained of blood and removed from an organism, it appears grey-white.[ citation needed ]

Venous system

Branches of inferior vena cava Major Veins.png
Branches of inferior vena cava

The largest veins in the human body are the venae cavae. These are two large veins which enter the right atrium of the heart from above and below. The superior vena cava carries blood from the arms and head to the right atrium of the heart, while the inferior vena cava carries blood from the legs and abdomen to the heart. The inferior vena cava is retroperitoneal and runs to the right and roughly parallel to the abdominal aorta along the spine. Large veins feed into these two veins, and smaller veins into these. Together this forms the venous system.

Whilst the main veins hold a relatively constant position, the position of veins person to person can display quite a lot of variation.[ citation needed ]

The pulmonary veins carry relatively oxygenated blood from the lungs to the heart. The superior and inferior venae cavae carry relatively deoxygenated blood from the upper and lower systemic circulations, respectively.

The portal venous system is a series of veins or venules that directly connect two capillary beds. Examples of such systems include the hepatic portal vein and hypophyseal portal system.

The peripheral veins carry blood from the limbs and hands and feet.

Microanatomy

Microscopically, veins have a thick outer layer made of connective tissue, called the tunica externa or tunica adventitia. During procedures requiring venous access such as venipuncture, one may notice a subtle "pop" as the needle penetrates this layer. The middle layer of bands of smooth muscle are called tunica media and are, in general, much thinner than those of arteries, as veins do not function primarily in a contractile manner and are not subject to the high pressures of systole, as arteries are. The interior is lined with endothelial cells called tunica intima. The precise location of veins varies much more from person to person than that of arteries. [3]

Function

Veins serve to return blood from organs to the heart. Veins are also called "capacitance vessels" because most of the blood volume (60%) is contained within veins. In systemic circulation oxygenated blood is pumped by the left ventricle through the arteries to the muscles and organs of the body, where its nutrients and gases are exchanged at capillaries. After taking up cellular waste and carbon dioxide in capillaries, blood is channeled through vessels that converge with one another to form venules, which continue to converge and form the larger veins. The de-oxygenated blood is taken by veins to the right atrium of the heart, which transfers the blood to the right ventricle, where it is then pumped through the pulmonary arteries to the lungs. In pulmonary circulation the pulmonary veins return oxygenated blood from the lungs to the left atrium, which empties into the left ventricle, completing the cycle of blood circulation.

The return of blood to the heart is assisted by the action of the muscle pump, and by the thoracic pump action of breathing during respiration. Standing or sitting for a prolonged period of time can cause low venous return from venous pooling (vascular) shock. Fainting can occur but usually baroreceptors within the aortic sinuses initiate a baroreflex such that angiotensin II and norepinephrine stimulate vasoconstriction and heart rate increases to return blood flow. Neurogenic and hypovolaemic shock can also cause fainting. In these cases, the smooth muscles surrounding the veins become slack and the veins fill with the majority of the blood in the body, keeping blood away from the brain and causing unconsciousness. Jet pilots wear pressurized suits to help maintain their venous return and blood pressure.

The arteries are perceived as carrying oxygenated blood to the tissues, while veins carry deoxygenated blood back to the heart. This is true of the systemic circulation, by far the larger of the two circuits of blood in the body, which transports oxygen from the heart to the tissues of the body. However, in pulmonary circulation, the arteries carry deoxygenated blood from the heart to the lungs, and veins return blood from the lungs to the heart. The difference between veins and arteries is their direction of flow (out of the heart by arteries, returning to the heart for veins), not their oxygen content. In addition, deoxygenated blood that is carried from the tissues back to the heart for reoxygenation in the systemic circulation still carries some oxygen, though it is considerably less than that carried by the systemic arteries or pulmonary veins.

Although most veins take blood back to the heart, there is an exception. Portal veins carry blood between capillary beds. For example, the hepatic portal vein takes blood from the capillary beds in the digestive tract and transports it to the capillary beds in the liver. The blood is then drained in the gastrointestinal tract and spleen, where it is taken up by the hepatic veins, and blood is taken back into the heart. Since this is an important function in mammals, damage to the hepatic portal vein can be dangerous. Blood clotting in the hepatic portal vein can cause portal hypertension, which results in a decrease of blood fluid to the liver.

Cardiac veins

The vessels that remove the deoxygenated blood from the heart muscle are known as cardiac veins. These include the great cardiac vein, the middle cardiac vein, the small cardiac vein, the smallest cardiac veins, and the anterior cardiac veins. Coronary veins carry blood with a poor level of oxygen, from the myocardium to the right atrium. Most of the blood of the coronary veins returns through the coronary sinus. The anatomy of the veins of the heart is very variable, but generally it is formed by the following veins: heart veins that go into the coronary sinus: the great cardiac vein, the middle cardiac vein, the small cardiac vein, the posterior vein of the left ventricle, and the vein of Marshall. Heart veins that go directly to the right atrium: the anterior cardiac veins, the smallest cardiac veins (Thebesian veins). [4]

Clinical significance

Diseases

Venous insufficiency

Venous insufficiency is the most common disorder of the venous system, and is usually manifested as spider veins or varicose veins. Several varieties of treatments are used, depending on the patient's particular type and pattern of veins and on the physician's preferences. Treatment can include Endovenous Thermal Ablation using radiofrequency or laser energy, vein stripping, ambulatory phlebectomy, foam sclerotherapy, lasers, or compression.

Postphlebitic syndrome is venous insufficiency that develops following deep vein thrombosis. [5]

Deep vein thrombosis

Deep vein thrombosis is a condition in which a blood clot forms in a deep vein. This is usually the veins of the legs, although it can also occur in the veins of the arms. Immobility, active cancer, obesity, traumatic damage and congenital disorders that make clots more likely are all risk factors for deep vein thrombosis. It can cause the affected limb to swell, and cause pain and an overlying skin rash. In the worst case, a deep vein thrombosis can extend, or a part of a clot can break off and land in the lungs, called pulmonary embolism.

The decision to treat deep vein thrombosis depends on its size, a person's symptoms, and their risk factors. It generally involves anticoagulation to prevents clots or to reduce the size of the clot.

Portal hypertension

The portal veins are found within the abdomen and carry blood through to the liver. Portal hypertension is associated with cirrhosis or disease of the liver, or other conditions such as an obstructing clot (Budd Chiari syndrome) or compression from tumours or tuberculosis lesions. When the pressure increases in the portal veins, a collateral circulation develops, causing visible veins such as oesophageal varices.

Other

Thrombophlebitis is an inflammatory condition of the veins related to blood clots.

Imaging

Video of venous valve in action Venous valve 00013.gif
Video of venous valve in action

Ultrasound, particularly duplex ultrasound, is a common way that veins can be seen.

Veins of clinical significance

The Batson Venous plexus, or simply Batson's Plexus, runs through the inner vertebral column connecting the thoracic and pelvic veins. These veins get their notoriety from the fact that they are valveless, which is believed to be the reason for metastasis of certain cancers.

The great saphenous vein is the most important superficial vein of the lower limb. First described by the Persian physician Avicenna, this vein derives its name from the word safina, meaning "hidden". This vein is "hidden" in its own fascial compartment in the thigh and exits the fascia only near the knee. Incompetence of this vein is an important cause of varicose veins of lower limbs.

The Thebesian veins within the myocardium of the heart are valveless veins that drain directly into the chambers of the heart. The coronary veins all empty into the coronary sinus which empties into the right atrium.

The dural venous sinuses within the dura mater surrounding the brain receive blood from the brain and also are a point of entry of cerebrospinal fluid from arachnoid villi absorption. Blood eventually enters the internal jugular vein.

Phlebology

Venous valves prevent reverse blood flow. Venous valve.svg
Venous valves prevent reverse blood flow.

Phlebology is the medical specialty devoted to the diagnosis and treatment of venous disorders. A medical specialist in phlebology is termed a phlebologist. A related image is called a phlebograph.

The American Medical Association added phlebology to their list of self-designated practice specialties in 2005. In 2007 the American Board of Phlebology (ABPh), subsequently known as the American Board of Venous & Lymphatic Medicine (ABVLM), was established to improve the standards of phlebologists and the quality of their patient care by establishing a certification examination, as well as requiring maintenance of certification. Although As of 2017 not a Member Board of the American Board of Medical Specialties (ABMS), the American Board of Venous & Lymphatic Medicine uses a certification exam based on ABMS standards.

The American Vein and Lymphatic Society (AVLS), formerly the American College of Phlebology (ACP) one of the largest medical societies in the world for physicians and allied health professionals working in the field of phlebology, has 2000 members. The AVLS encourages education and training to improve the standards of medical practitioners and the quality of patient care.

The American Venous Forum (AVF) is a medical society for physicians and allied health professionals dedicated to improving the care of patients with venous and lymphatic disease. The majority of its members manage the entire spectrum of venous and lymphatic diseases – from varicose veins to congenital abnormalities to deep vein thrombosis to chronic venous diseases. Founded in 1987, the AVF encourages research, clinical innovation, hands-on education, data collection and patient outreach.

History

Human anatomical chart of blood vessels, with heart, lungs, liver and kidneys included. Other organs are numbered and arranged around it. Before cutting out the figures on this page, Vesalius suggests that readers glue the page onto parchment and gives instructions on how to assemble the pieces and paste the multilayered figure onto a base "muscle man" illustration. "Epitome", fol.14a. HMD Collection, WZ 240 V575dhZ 1543. Charta ex qva figvram parare convenit, illi qvae nervorvm seriem exprimit appendendam, 1543..JPG
Human anatomical chart of blood vessels, with heart, lungs, liver and kidneys included. Other organs are numbered and arranged around it. Before cutting out the figures on this page, Vesalius suggests that readers glue the page onto parchment and gives instructions on how to assemble the pieces and paste the multilayered figure onto a base "muscle man" illustration. "Epitome", fol.14a. HMD Collection, WZ 240 V575dhZ 1543.

The earliest known writings on the circulatory system are found in the Ebers Papyrus (16th century BCE), an ancient Egyptian medical papyrus containing over 700 prescriptions and remedies, both physical and spiritual. In the papyrus, it acknowledges the connection of the heart to the arteries. The Egyptians thought air came in through the mouth and into the lungs and heart. From the heart, the air travelled to every member through the arteries. Although this concept of the circulatory system is only partially correct, it represents one of the earliest accounts of scientific thought.

In the 6th century BCE, the knowledge of circulation of vital fluids through the body was known to the Ayurvedic physician Sushruta in ancient India. [6] He also seems to have possessed knowledge of the arteries, described as 'channels' by Dwivedi & Dwivedi (2007). [6] The valves of the heart were discovered by a physician of the Hippocratean school around the 4th century BCE. However their function was not properly understood then. Because blood pools in the veins after death, arteries look empty. Ancient anatomists assumed they were filled with air and that they were for transport of air.

The Greek physician, Herophilus, distinguished veins from arteries but thought that the pulse was a property of arteries themselves. Greek anatomist Erasistratus observed that arteries that were cut during life bleed. He ascribed the fact to the phenomenon that air escaping from an artery is replaced with blood that entered by very small vessels between veins and arteries. Thus he apparently postulated capillaries but with reversed flow of blood. [7]

In 2nd century AD Rome, the Greek physician Galen knew that blood vessels carried blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. Growth and energy were derived from venous blood created in the liver from chyle, while arterial blood gave vitality by containing pneuma (air) and originated in the heart. Blood flowed from both creating organs to all parts of the body where it was consumed and there was no return of blood to the heart or liver. The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries themselves.

Galen believed that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through 'pores' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled.

In 1025, The Canon of Medicine by the Persian physician, Avicenna, "erroneously accepted the Greek notion regarding the existence of a hole in the ventricular septum by which the blood traveled between the ventricles." While also refining Galen's erroneous theory of the pulse, Avicenna provided the first correct explanation of pulsation: "Every beat of the pulse comprises two movements and two pauses. Thus, expansion : pause : contraction : pause. [...] The pulse is a movement in the heart and arteries ... which takes the form of alternate expansion and contraction." [8]

In 1242, the Arabian physician, Ibn al-Nafis, became the first person to accurately describe the process of pulmonary circulation, [9] for which he has been described as the Arab Father of Circulation. [10] Ibn al-Nafis stated in his Commentary on Anatomy in Avicenna's Canon:

"...the blood from the right chamber of the heart must arrive at the left chamber but there is no direct pathway between them. The thick septum of the heart is not perforated and does not have visible pores as some people thought or invisible pores as Galen thought. The blood from the right chamber must flow through the vena arteriosa (pulmonary artery) to the lungs, spread through its substances, be mingled there with air, pass through the arteria venosa (pulmonary vein) to reach the left chamber of the heart and there form the vital spirit..."

In addition, Ibn al-Nafis had an insight into what would become a larger theory of the capillary circulation. He stated that "there must be small communications or pores (manafidh in Arabic) between the pulmonary artery and vein," a prediction that preceded the discovery of the capillary system by more than 400 years. [11] Ibn al-Nafis' theory, however, was confined to blood transit in the lungs and did not extend to the entire body.

Michael Servetus was the first European to describe the function of pulmonary circulation, although his achievement was not widely recognized at the time, for a few reasons. He firstly described it in the "Manuscript of Paris" [12] [13] (near 1546), but this work was never published. And later he published this description, but in a theological treatise, Christianismi Restitutio, not in a book on medicine. Only three copies of the book survived but these remained hidden for decades, the rest were burned shortly after its publication in 1553 because of persecution of Servetus by religious authorities.

Better known discovery of pulmonary circulation was by Vesalius's successor at Padua, Realdo Colombo, in 1559.

Image of veins from William Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus William Harvey ( 1578-1657) Venenbild.jpg
Image of veins from William Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus

Finally, William Harvey, a pupil of Hieronymus Fabricius (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments, and published Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus in 1628, which "demonstrated that there had to be a direct connection between the venous and arterial systems throughout the body, and not just the lungs. Most importantly, he argued that the beat of the heart produced a continuous circulation of blood through minute connections at the extremities of the body. This is a conceptual leap that was quite different from Ibn al-Nafis' refinement of the anatomy and bloodflow in the heart and lungs." [14] This work, with its essentially correct exposition, slowly convinced the medical world. However, Harvey was not able to identify the capillary system connecting arteries and veins; these were later discovered by Marcello Malpighi in 1661.

In 1956, André Frédéric Cournand, Werner Forssmann and Dickinson W. Richards were awarded the Nobel Prize in Medicine "for their discoveries concerning heart catheterization and pathological changes in the circulatory system." [15] In his Nobel lecture, Forssmann credits Harvey as birthing cardiology with the publication of his book in 1628. [16]

In the 1970s, Diana McSherry developed computer-based systems to create images of the circulatory system and heart without the need for surgery. [17]

See also

Related Research Articles

Artery blood vessels that carry blood away from the heart

An artery is a blood vessel that takes blood away from the heart to all parts of the body. Most arteries carry oxygenated blood; the two exceptions are the pulmonary and the umbilical arteries, which carry deoxygenated blood to the organs that oxygenate it. The effective arterial blood volume is that extracellular fluid which fills the arterial system.

Heart organ for the circulation of blood in animal circulatory systems

The heart is a muscular organ in most animals, which pumps blood through the blood vessels of the circulatory system. Blood provides the body with oxygen and nutrients, as well as assisting in the removal of metabolic wastes. In humans, the heart is located between the lungs, in the middle compartment of the chest.

Blood vessel a tubular structure which carries blood

The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from the tissues. Blood vessels are needed to sustain life, because all of the body’s tissues rely on their functionality.

Circulatory system Organ system for circulating blood in animals

The circulatory system, also called the cardiovascular system or the vascular system, is an organ system that permits blood to circulate and transport nutrients, oxygen, carbon dioxide, hormones, and blood cells to and from the cells in the body to provide nourishment and help in fighting diseases, stabilize temperature and pH, and maintain homeostasis.

Coronary circulation circulation of blood in the blood vessels of the heart muscle (myocardium)

Coronary circulation is the circulation of blood in the blood vessels that supply the heart muscle (myocardium). Coronary arteries supply oxygenated blood to the heart muscle, and cardiac veins drain away the blood once it has been deoxygenated. Because the rest of the body, and most especially the brain, needs a steady supply of oxygenated blood that is free of all but the slightest interruptions, the heart is required to function continuously. Therefore its circulation is of major importance not only to its own tissues but to the entire body and even the level of consciousness of the brain from moment to moment. Interruptions of coronary circulation quickly cause heart attacks, in which the heart muscle is damaged by oxygen starvation. Such interruptions are usually caused by ischemic heart disease and sometimes by embolism from other causes like obstruction in blood flow through vessels.

Embolism disease of arteries, arterioles and capillaries

An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule, a bubble of air or other gas, or foreign material. An embolism can cause partial or total blockage of blood flow in the affected vessel. Such a blockage may affect a part of the body distant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called a thromboembolism.

Pulmonary artery artery in the pulmonary circulation that carries deoxygenated blood from the heart to the lungs

A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the main pulmonary artery or pulmonary trunk from the heart, and the smallest ones are the arterioles, which lead to the capillaries that surround the pulmonary alveoli.

Venous blood

Venous blood is deoxygenated blood which travels from the peripheral vessels, through the venous system into the right atrium of the heart. Deoxygenated blood is then pumped by the right ventricle to the lungs via the pulmonary artery which is divided in two branches, left and right to the left and right lungs respectively. Blood is oxygenated in the lungs and returns to the left atrium through the pulmonary veins.

Pulmonary circulation The part of the circulatory system which carries blood from heart to lungs and back to the heart

The pulmonary circulation is the portion of the circulatory system which carries deoxygenated blood away from the right ventricle, to the lungs, and returns oxygenated blood to the left atrium and ventricle of the heart. The term pulmonary circulation is readily paired and contrasted with the systemic circulation. The vessels of the pulmonary circulation are the pulmonary arteries and the pulmonary veins.

Pulmonary vein The veins that transfer oxygenated blood from the lungs to the heart

The pulmonary veins are the veins that transfer oxygenated blood from the lungs to the heart. The largest pulmonary veins are the four main pulmonary veins, two from each lung that drain into the left atrium of the heart. The pulmonary veins are part of the pulmonary circulation.

Fontan procedure

The Fontan procedure or Fontan–Kreutzer procedure is a palliative surgical procedure used in children with univentricular hearts. It involves diverting the venous blood from the inferior vena cava (IVC) and superior vena cava (SVC) to the pulmonary arteries without passing through the morphologic right ventricle; i.e., the systemic and pulmonary circulations are placed in series with the functional single ventricle. The procedure was initially performed 1971 by Francis Fontan and Eugene Baudet, and further described in 1973 by Guillermo Kreutzer.

Cardiac catheterization insertion of a catheter into a chamber or vessel of the heart

Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done both for diagnostic and interventional purposes. A common example of cardiac catheterization is coronary catheterization that involves catheterization of the coronary arteries for coronary artery disease and myocardial infarctions. Catheterization is most often performed in special laboratories with fluoroscopy and highly maneuverable tables. These "cath labs" are often equipped with cabinets of catheters, stents, balloons, etc. of various sizes to increase efficiency. Monitors show the fluoroscopy imaging, EKG, pressure waves, and more.

Atrium (heart) chamber of the heart

The atrium is the upper chamber through which blood enters the ventricles of the heart. There are two atria in the human heart – the left atrium receives blood from the pulmonary (lung) circulation, and the right atrium receives blood from the venae cavae. The atria receive blood while relaxed (diastole), then contract (systole) to move blood to the ventricles. All animals with a closed circulatory system have at least one atrium. Humans have two atria.

Fetal circulation

In animals that give live birth, the fetal circulation is the circulatory system of a fetus. The term usually encompasses the entire fetoplacental circulation, which includes the umbilical cord and the blood vessels within the placenta that carry fetal blood.

Levo-Transposition of the great arteries is an acyanotic congenital heart defect in which the primary arteries are transposed, with the aorta anterior and to the left of the pulmonary artery; the morphological left and right ventricles with their corresponding atrioventricular valves are also transposed.

A right-to-left shunt is a cardiac shunt which allows blood to flow from the right heart to the left heart. This terminology is used both for the abnormal state in humans and for normal physiological shunts in reptiles.

A cardiac shunt is a pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system. It may be described as right-left, left-right or bidirectional, or as systemic-to-pulmonary or pulmonary-to-systemic. The direction may be controlled by left and/or right heart pressure, a biological or artificial heart valve or both. The presence of a shunt may also affect left and/or right heart pressure either beneficially or detrimentally.

Smallest cardiac veins

The smallest cardiac veins are minute valveless veins in the walls of all four heart chambers. The veins are sometimes accurately referred to as vessels, but they are frequently confused with a distinct set of artery connections eponymously referred to as the "vessels of Wearn". In his 1928 publication, Wearn himself referred to the arterio-cameral connections as thebesian. However, Wearn's 1933 and 1941 publications emphatically described the thebesian veins as distinct from arterio-cameral vessels.

The Senning procedure is an atrial switch heart operation performed to treat transposition of the great arteries. It is named after its inventor, the Swedish cardiac surgeon Åke Senning (1915–2000), also known for implanting the first permanent cardiac pacemaker in 1958.

The Commentary on Anatomy in Avicenna's Canon is a manuscript written in the 13th century by the Arab physician Ibn al-Nafis. The manuscript was discovered in 1924 in the archives of the Prussian State Library in Berlin, Germany. It contains the earliest descriptions of the coronary circulation and pulmonary circulation systems.

References

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  12. Gonzalez Etxeberria, Patxi (2011) Amor a la verdad, el – vida y obra de Miguel servet [The love for truth. Life and work of Michael Servetus]. Navarro y Navarro, Zaragoza, collaboration with the Government of Navarra, Department of Institutional Relations and Education of the Government of Navarra. ISBN   8423532666 pp. 215–228 & 62nd illustration (XLVII)
  13. Michael Servetus Research Study with graphical proof on the Manuscript of Paris and many other manuscripts and new works by Servetus
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  15. "The Nobel Prize in Physiology or Medicine 1956". Nobel Foundation. Retrieved 28 July 2007.
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Further reading