Gangrene

Gangrene is a type of tissue death caused by a lack of blood supply.[4] Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness.[1] The feet and hands are most commonly affected.[1] Certain types may present with a fever or sepsis.[1]

Risk factors include diabetes, peripheral arterial disease, smoking, major trauma, alcoholism, HIV/AIDS, frostbite, and Raynaud's syndrome.[3][4] It can be classified as dry gangrene, wet gangrene, gas gangrene, internal gangrene, and necrotizing fasciitis.[3] The diagnosis of gangrene is based on symptoms and supported by tests such as medical imaging.[6]

Treatment may involve surgery to remove the dead tissue, antibiotics to treat any infection, and efforts to address the underlying cause.[5] Surgical efforts may include debridement, amputation, or the use of maggot therapy.[5] Efforts to treat the underlying cause may include bypass surgery or angioplasty.[5] In certain cases, hyperbaric oxygen therapy may be useful.[5] How commonly the condition occurs is unknown.[2]

Gangrene
Other namesGangrenous necrosis
GangreneFoot
Dry gangrene affecting the toes as a result of peripheral artery disease
SpecialtyInfectious disease, surgery
SymptomsChange in skin color to red or black, numbness, pain, skin breakdown, coolness[1]
ComplicationsSepsis, amputation[1][2]
TypesDry, wet, gas, internal, necrotizing fasciitis[3]
Risk factorsDiabetes, peripheral arterial disease, smoking, major trauma, alcoholism, HIV/AIDS, frostbite, Raynaud's syndrome[3][4]
TreatmentSurgery, antibiotics[5]
FrequencyUnknown[2]

Signs and symptoms

Plate II Mortification (gangrene), Robert Carswell 1830s Wellcome L0074380
An illustration showing four different stages of gangrene, including one (Fig. 4 top right) caused by an obstacle to the return of the venous blood due to heart disease.

Symptoms may include a change in skin color to red or black, numbness, pain, skin breakdown, and coolness.[1] The feet and hands are most commonly involved.[1]

Causes

Gangrene is caused by a critically insufficient blood supply (e.g., peripheral vascular disease) or infection.[3][7][8] It is associated with diabetes[9] and long-term tobacco smoking.[4][3]

Dry gangrene

Dry gangrene is a form of coagulative necrosis that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. It is not a disease itself, but a symptom of other diseases.[10] Dry gangrene is often due to peripheral artery disease, but can be due to acute limb ischemia. The limited oxygen in the ischemic limb limits putrefaction and bacteria fail to survive. The affected part is dry, shrunken, and dark reddish-black. The line of separation usually brings about complete separation, with eventual falling off of the gangrenous tissue if it is not removed surgically, a process called autoamputation.

Dry gangrene is the end result of chronic ischemia without infection. If ischemia is detected early, when  ischemic wounds rather than gangrene are present, the process can be treated by revascularization (via vascular bypass or angioplasty).[11] However, once gangrene has developed, the affected tissues are not salvageable.[12] Because dry gangrene is not accompanied by infection, it is not as emergent as gas gangrene or wet gangrene, both of which have a risk of sepsis. Over time, dry gangrene may develop into wet gangrene if an infection develops in the dead tissues.[13]

Diabetes mellitus is a risk factor for peripheral vascular disease, thus for dry gangrene, but also a risk factor for wet gangrene, particularly in patients with poorly controlled blood sugar levels, as elevated serum glucose creates a favorable environment for bacterial infection.[14]

Wet gangrene

Wet gangrene of the foot
Wet gangrene of the foot

Wet, or infected, gangrene is characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by saprogenic microorganisms (Clostridium perfringens or Bacillus fusiformis, for example), which cause tissue to swell and emit a fetid smell. Wet gangrene usually develops rapidly due to blockage of venous (mainly) or arterial blood flow. The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis and finally death. The affected part is edematous, soft, putrid, rotten, and dark.

Because of the high mortality associated with infected gangrene, an emergency salvage amputation, such as a guillotine amputation, is often needed to limit systemic effects of the infection.[15] Such an amputation can be converted to a formal amputation, such as a below- or above-knee amputation.[15]

Gas gangrene

Gas gangrene is a bacterial infection that produces gas within tissues. It can be caused by Clostridium, most commonly alpha toxin-producing C. perfringens, or various nonclostridial species.[8][16] Infection spreads rapidly as the gases produced by the bacteria expand and infiltrate healthy tissue in the vicinity. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a medical emergency.

Gas gangrene is caused by bacterial exotoxin-producing clostridial species, which are mostly found in soil, and other anaerobes such as Bacteroides and anaerobic streptococci. These environmental bacteria may enter the muscle through a wound and subsequently proliferate in necrotic tissue and secrete powerful toxins, which destroy nearby tissue, generating gas at the same time. A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case.[17]

Gas gangrene can cause necrosis, gas production, and sepsis. Progression to toxemia and shock is often very rapid.

Other types

Treatment

Surgical removal of all dead tissue is the mainstay of treatment for gangrene. Often, gangrene is associated with underlying infection, thus the gangrenous tissue must be debrided to hinder the spread of the associated infection. The extent of surgical debridement needed depends on the extent of the gangrene, and may be limited to the removal of a finger, toe, or ear, but in severe cases may involve a limb amputation.

Dead tissue alone does not require debridement, and in some cases, such as dry gangrene, the affected part falls off (autoamputates), making surgical removal unnecessary.

As infection is often associated with gangrene, antibiotics are often a critical component of its treatment. The life-threatening nature of gangrene requires treatment with intravenous antibiotics in an inpatient setting.

After the gangrene is treated with debridement and antibiotics, the underlying cause can be treated. In the case of gangrene due to critical limb ischemia, revascularization can be performed to treat the underlying peripheral artery disease.

Ischemic disease of the legs is the most common reason for amputations. In about a quarter of these cases, the other side requires amputation in the next three years.[20]

In 2005, an estimated 1.6 million individuals in the United States were living with the loss of a limb caused by either trauma, cancer, or vascular disease; these estimates are expected to more than double to 3.6 million such individuals by 2050.[21] Antibiotics alone are not effective because they may not penetrate infected tissues sufficiently.[22] Hyperbaric oxygen therapy treatment is used to treat gas gangrene. It increases pressure and oxygen content to allow blood to carry more oxygen to inhibit anaerobic organism growth and reproduction.[23] A regenerative medicine therapy was developed by Dr. Peter DeMarco to treat diabetic gangrene to avoid amputations. Growth factors, hormones, and skin grafts have also been used to accelerate healing for gangrene and other chronic wounds.

Angioplasty should be considered if severe blockage in lower leg vessels (tibial and peroneal artery) leads to gangrene.[24]

History

Wallen wounded by Minie ball
Confederate Army Private Milton E. Wallen lies in bed with a gangrenous amputated arm

As early as 1028, flies and maggots were commonly used to treat chronic wounds or ulcers to prevent or arrest necrotic spread,[25] as some species of maggots consume only dead flesh, leaving nearby living tissue unaffected. This practice largely died out after the introduction of antibiotics, acetonitrile, and enzyme to the range of treatments for wounds. In recent times, however, maggot therapy has regained some credibility and is sometimes employed with great efficacy in cases of chronic tissue necrosis.

The French Baroque composer Jean-Baptiste Lully contracted gangrene in January 1687 when, while conducting a performance of his Te Deum, he stabbed his own toe with his pointed staff (which was used as a baton). The disease spread to his leg, but the composer refused to have his toe amputated, which eventually led to his death in March of that year.[26]

French King Louis XIV died of gangrene in his leg on 1 September 1715, four days prior to his 77th birthday.[27]

John M. Trombold wrote: "Middleton Goldsmith, a surgeon in the Union Army during the American Civil War, meticulously studied hospital gangrene and developed a revolutionary treatment regimen. The cumulative Civil War hospital gangrene mortality was 45%. Goldsmith's method, which he applied to over 330 cases, yielded a mortality under 3%."[28] Goldsmith advocated the use of debridement and topical and injected bromide solutions on infected wounds to reduce the incidence and virulence of “poisoned miasma.” Copies of his book[29] were issued to Union surgeons to encourage the use of his methods.[30]

Etymology

The etymology of gangrene derives from the Latin word gangraena and from the Greek gangraina (γάγγραινα), which means "putrefaction of tissues".[31] It has no etymological connection with the word green, despite the affected areas turning black, green, or yellowish brown. It is coincidence that, in Lowland Scots, the words "gang green" (go green) can be said to be an eggcorn for gangrene, as it describes the symptoms of the affliction.

References

  1. ^ a b c d e f g "Gangrene Symptoms". NHS. 13 October 2015. Retrieved 12 December 2017.
  2. ^ a b c "Gangrene". patient.info. 12 March 2014. Retrieved 12 December 2017.
  3. ^ a b c d e f "Gangrene Causes". NHS. 13 October 2015. Retrieved 12 December 2017.
  4. ^ a b c d "Gangrene". NHS. 13 October 2015. Retrieved 12 December 2017.
  5. ^ a b c d e "Gangrene Treatment". NHS. Retrieved 12 December 2017.
  6. ^ "Gangrene Diagnosis". NHS. 13 October 2015. Retrieved 12 December 2017.
  7. ^ Gardner, AW; Afaq, A (November–December 2008). "Management of lower extremity peripheral arterial disease". Journal of Cardiopulmonary Rehabilitation and Prevention. 28 (6): 349–57. doi:10.1097/HCR.0b013e31818c3b96. PMC 2743684. PMID 19008688.
  8. ^ a b Yang, Z; Hu, J; Qu, Y; Sun, F; Leng, X; Li, H; Zhan, S (3 December 2015). "Interventions for treating gas gangrene". The Cochrane Database of Systematic Reviews (12): CD010577. doi:10.1002/14651858.CD010577.pub2. PMID 26631369.
  9. ^ Korzon-Burakowska, A; Dziemidok, P (December 2011). "Diabetic foot-the need for comprehensive multidisciplinary approach". Annals of Agricultural and Environmental Medicine. 18 (2): 314–17. PMID 22216805.
  10. ^ Smith, Tyler (2015). Gangrene Management: Today and Tomorrow. Hayle Medical. ISBN 978-1632412232.
  11. ^ Aiello A, Anichini R, Brocco E, Caravaggi C, Chiavetta A, Cioni R, Da Ros R, De Feo ME, Ferraresi R, Florio F, Gargiulo M, Galzerano G, Gandini R, Giurato L, Graziani L, Mancini L, Manzi M, Modugno P, Setacci C, Uccioli L (2014). "Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE)". Nutr Metab Cardiovasc Dis. 24 (4): 355–69. doi:10.1016/j.numecd.2013.12.007. PMID 24486336.
  12. ^ Gerhard-Herman, MD; Gornik, HL; Barrett, C; Barshes, NR; Corriere, MA; Drachman, DE; Fleisher, LA; Fowkes, FG; Hamburg, NM; Kinlay, S; Lookstein, R; Misra, S; Mureebe, L; Olin, JW; Patel, RA; Regensteiner, JG; Schanzer, A; Shishehbor, MH; Stewart, KJ; Treat-Jacobson, D; Walsh, ME (2017). "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". Circulation. 135 (12): e726–79. doi:10.1161/CIR.0000000000000471. PMC 5477786. PMID 27840333.
  13. ^ Nather, Aziz (2013). The diabetic foot. ISBN 978-9814417006.
  14. ^ Vayvada, H; Demirdover, C; Menderes, A; Karaca, C (August 2013). "Necrotising fasciitis in the central part of the body: diagnosis, management and review of the literature". International Wound Journal. 10 (4): 466–72. doi:10.1111/j.1742-481x.2012.01006.x. PMID 22694053.
  15. ^ a b Tisi, PV; Than, MM (8 April 2014). "Type of incision for below knee amputation". The Cochrane Database of Systematic Reviews. 4 (4): CD003749. doi:10.1002/14651858.CD003749.pub3. PMID 24715679.
  16. ^ Sakurai, J.; Nagahama, M.; Oda, M. (November 2004). "Clostridium perfringens alpha-toxin: characterization and mode of action". Journal of Biochemistry. 136 (5): 569–74. doi:10.1093/jb/mvh161. PMID 15632295.
  17. ^ Chi CH, Chen KW, Huang JJ, Chuang YC, Wu MH (December 1995). "Gas composition in Clostridium septicum gas gangrene". Journal of the Formosan Medical Association. 94 (12): 757–59. PMID 8541740.
  18. ^ Levenson, RB; Singh, AK; Novelline, RA (March–April 2008). "Fournier gangrene: role of imaging". Radiographics. 28 (2): 519–28. doi:10.1148/rg.282075048. PMID 18349455.
  19. ^ Warkentin, TE (August 2010). "Agents for the treatment of heparin-induced thrombocytopenia". Hematology/Oncology Clinics of North America. 24 (4): 755–75. doi:10.1016/j.hoc.2010.05.009. PMID 20659659.
  20. ^ Amputations of the Lower Extremity at eMedicine
  21. ^ Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R (March 2008). "Estimating the prevalence of limb loss in the United States: 2005 to 2050". Arch Phys Med Rehabil. 89 (3): 422–29. doi:10.1016/j.apmr.2007.11.005. PMID 18295618.
  22. ^ Lipsky BA (December 1999). "Evidence-based antibiotic therapy of diabetic foot infections". FEMS Immunol. Med. Microbiol. 26 (3–4): 267–76. doi:10.1016/s0928-8244(99)00143-1. PMID 10575138.
  23. ^ Liu R, Li L, Yang M, Boden G, Yang G (2013). "Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers". Mayo Clin. Proc. 88 (2): 166–75. doi:10.1016/j.mayocp.2012.10.021. PMID 23374620.
  24. ^ "Angioplasty and stent placement – peripheral arteries". Retrieved July 24, 2013.
  25. ^ Shi, Eric; Shofler, David (2014). "Maggot debridement therapy: A systematic review". British Journal of Community Nursing. 19: S6–S13. doi:10.12968/bjcn.2014.19.Sup12.S6. PMID 25478859.
  26. ^ "Music Trivia – The Death of Lully". The Musician's Lounge. Utah Symphony Orchestra. August 2010. Retrieved March 7, 2017.
  27. ^ Laurenson, John (21 November 2015). "The strange death of Louis XIV". The Spectator. Retrieved 12 March 2017.
  28. ^ Trombold JM (2011). "Gangrene therapy and antisepsis before lister: the civil war contributions of Middleton Goldsmith of Louisville". Am Surg. 77 (9): 1138–43. PMID 21944621.
  29. ^ A report on hospital gangrene, erysipelas and pyaemia. 1863
  30. ^ Watson, Dr. Scott. "Hospital Gangrene During The Civil War – Civil War Medicine". Retrieved 2014-04-15.
  31. ^ Liddell & Scott's Lexicon, Oxford University Press, 1963 edition

External links

External resources
  • Media related to Gangrene at Wikimedia Commons
Chronic undermining burrowing ulcer

Chronic undermining burrowing ulcer (also known as Meleney gangrene, or Meleney's ulcer) is a cutaneous condition that is a postoperative, progressive bacterial gangrene. It is seen in immunocompromised individuals, mostly after post abdominal surgery and rapidly spreads to involve a large area.

Clostridium enterotoxin

Clostridium enterotoxins are toxins produced by Clostridium species.Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in the soil. Among the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhea cases. The use of toxins to damage the host is a method deployed by many bacterial pathogens.

The major virulence factor of C. perfringens is the CPE enterotoxin, which is secreted upon invasion of the host gut, and contributes to food poisoning and other gastrointestinal illnesses. It has a molecular weight of 35.3kDa, and is responsible for the disintegration of tight junctions between epithelial cells in the gut. This mechanism is mediated by host claudin-3 and claudin-4 receptors, situated at the tight junctions.Clostridium enterotoxin is a nine-stranded beta sheet sandwich in shape. It has been determined that it is very similar to other spore-forming bacteria. The PFAM ID is a clenterotox. The binding site is between beta sheets eight and nine. This allows the human claudin-3,4,6,7,8 and 14 to bind but not 1,2,5, and 10. The way the protein work is it destroys the cell membrane structure of animals by binding to claudin family proteins. These are components of tight junctions of the epithelial cell membrane.

Clostridium perfringens

Clostridium perfringens (formerly known as C. welchii, or Bacillus welchii) is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.C. perfringens is one of the most common causes of food poisoning in the United States, alongside norovirus, Salmonella, Campylobacter, and Staphylococcus aureus. However, it can sometimes be ingested and cause no harm.Infections due to C. perfringens show evidence of tissue necrosis, bacteremia, emphysematous cholecystitis, and gas gangrene, which is also known as clostridial myonecrosis. The toxin involved in gas gangrene is known as α-toxin, which inserts into the plasma membrane of cells, producing gaps in the membrane that disrupt normal cellular function. C. perfringens can participate in polymicrobial anaerobic infections. It is commonly encountered in infections as a component of the normal flora. In this case, its role in disease is minor.

The action of C. perfringens on dead bodies is known to mortuary workers as tissue gas. It causes extremely accelerated decomposition, and cannot be stopped by normal embalming measures. These bacteria are resistant to the presence of formaldehyde in normal concentrations.

Clostridium perfringens alpha toxin

Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.

Collagenase

Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as Clostridium. They are considered a virulence factor, facilitating the spread of gas gangrene. They normally target the connective tissue in muscle cells and other body organs.Collagen, a key component of the animal extracellular matrix, is made through cleavage of pro-collagen by collagenase once it has been secreted from the cell. This stops large structures from forming inside the cell itself.

In addition to being produced by some bacteria, collagenase can be made by the body as part of its normal immune response. This production is induced by cytokines, which stimulate cells such as fibroblasts and osteoblasts, and can cause indirect tissue damage.

Dermatitis gangrenosa

Dermatitis gangrenosa (also known as "Gangrene of the skin") is a cutaneous condition caused by infection by Clostridium resulting in a necrosis and sloughing of the skin.

Fournier gangrene

Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia and/or perineum. It commonly occurs in older men, but it

can also occur in women and children. It is more likely to occur in diabetics, alcoholics, or those who are immunocompromised.

About one per 62,500 males are affected per year. Males are affected about 40 times more often than females. It was first described by Baurienne in 1764 and is named after a French venereologist, Jean Alfred Fournier, following five cases he presented in clinical lectures in 1883.

Gangrene (group)

Gangrene is an American hip hop and record production duo, which consists of rapper/producers The Alchemist and Oh No. The Alchemist and Oh No, MCs and producers in their own right, weren't acquainted until they met at a show headlined by Dilated Peoples member and mutual friend, Evidence. The Alchemist contacted Oh No and proposed a collaborative project. From that point they "just clicked," says Oh No. "I sent him a verse and a beat, and he sent a beat and a verse." The creative sparring continued, and they began to refer to the work as Gangrene.

In 2013, Gangrene, Tangerine Dream and Woody Jackson scored and composed the original score for Grand Theft Auto V by Rockstar Games.

Gas gangrene

Gas gangrene (also known as clostridial myonecrosis and myonecrosis) is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States.Myonecrosis is a condition of necrotic damage, specific to muscle tissue. It is often seen in infections with C. perfringens or any of myriad soil-borne anaerobic bacteria. Bacteria cause myonecrosis by specific exotoxins. These microorganisms are opportunistic and, in general, enter the body through significant skin breakage. Gangrenous infection by soil-borne bacteria was common in the combat injuries of soldiers well into the 20th century, because of non-sterile field surgery and the basic nature of care for severe projectile wounds.Other causes of myonecrosis include envenomation by snakes of the genus Bothrops (family Viperidae), ischemic necrosis, caused by vascular blockage (e.g., diabetes type II), tumours that block or hoard blood supply, and disseminated intravascular coagulation or other thromboses.

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Necrosis

Necrosis (from the Greek νέκρωσις "death, the stage of dying, the act of killing" from νεκρός "dead") is a form of cell injury which results in the premature death of cells in living tissue by autolysis.Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma which result in the unregulated digestion of cell components.

In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death.

While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated, and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space.This initiates in the surrounding tissue an inflammatory response which attracts leukocytes and nearby phagocytes which eliminate the dead cells by phagocytosis. However, microbial damaging substances released by leukocytes would create collateral damage to surrounding tissues. This excess collateral damage inhibits the healing process. Thus, untreated necrosis results in a build-up of decomposing dead tissue and cell debris at or near the site of the cell death. A classic example is gangrene. For this reason, it is often necessary to remove necrotic tissue surgically, a procedure known as debridement.

Necrotizing fasciitis

Necrotizing fasciitis (NF), commonly known as flesh-eating disease, is an infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.Typically, the infection enters the body through a break in the skin such as a cut or burn. Risk factors include poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. It is not typically spread between people. The disease is classified into four types, depending on the infecting organism. Between 55 and 80% of cases involve more than one type of bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of cases. Medical imaging is helpful to confirm the diagnosis.Necrotizing fasciitis may be prevented with proper wound care and handwashing. It is usually treated with surgery to remove the infected tissue, and intravenous antibiotics. Often, a combination of antibiotics is used, such as penicillin G, clindamycin, vancomycin, and gentamicin. Delays in surgery are associated with a much higher risk of death. Even with high-quality treatment, the risk of death is between 25 and 35%.Necrotizing fasciitis occurs in about 0.4 people per 100,000 per year in the US, and about 1 per 100,000 in Western Europe. Both sexes are affected equally. It becomes more common among older people and is rare in children. It has been described at least since the time of Hippocrates. The term "necrotizing fasciitis" first came into use in 1952.

Nicholas van Hoorn

Nicholas van Hoorn (c. 1635 in Vlissingen – buried 24 June 1683, in Isla Mujeres) was a merchant sailor, privateer and pirate. He was born in the Netherlands and died near Veracruz after being wounded on the Isla de Sacrificios. Nikolaas or Klaas was engaged in the Dutch merchant service from about 1655 until 1659, and then bought a vessel with his savings. With a band of reckless men whom he had enlisted, he became a terror to the commerce of the Dutch Republic and the Spanish Empire. Later he had several ships in his employment and obtained such notoriety that some governments were willing to employ him against their enemies.

Noma (disease)

Noma or (also known as cancrum oris) is a rapidly progressive often gangrenous infection of the mouth and face.

Pyoderma gangrenosum

Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. Pyoderma gangrenosum is not infectious.Treatments may include corticosteroids, ciclosporin, infliximab, or canakinumab.The disease was identified in 1930. It affects approximately 1 person in 100,000 in the population. Though it can affect people of any age, it mostly affects people in their 40s and 50s.

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The Alchemist (musician)

Daniel Alan Maman (born October 25, 1977), professionally known as The Alchemist (or simply Alchemist), is a Jewish American record producer, disc jockey (DJ) and rapper. He began his music career in 1991 in the hip hop duo The Whooliganz under the moniker Mudfoot, along with now-actor Scott Caan (whose moniker was "Mad Skillz"). After rising to prominence in the late 1990s, as a close associate of Dilated Peoples and Mobb Deep, he went on to produce for many of hip hop's leading artists in the 2000s, and has been hailed as one of the genre's leading producers. He is currently working as a DJ with Action Bronson. He produces for many artists, most of his recent production is for a close group of frequent collaborative rappers. He focuses on producing entire albums for rappers and Instrumental projects of his own.

Together with his longtime collaborator Oh No (with whom he forms the group Gangrene), Woody Jackson and Tangerine Dream, he composed the official score to the 2013 video game Grand Theft Auto V.

Thromboangiitis obliterans

Not to be confused with Berger's disease (IgA nephropathy)Thromboangiitis obliterans, also known as Buerger disease (English , German /byrgər/), is a recurring progressive inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet. It is strongly associated with use of tobacco products, primarily from smoking, but is also associated with smokeless tobacco.

Trench foot

Trench foot is a medical condition caused by prolonged exposure of the feet to damp, unsanitary, and cold conditions. It is one of many immersion foot syndromes. The use of the word trench in the name of this condition is a reference to trench warfare, mainly associated with World War I.

Symptoms and signs relating to the cardiovascular system (R00–R03, 785)
Chest pain
Auscultation
Pulse
Vascular disease
Other
Shock
Principles of pathology
Anatomical pathology
Clinical pathology

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