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Gout

From Wikipedia, in a visual modern way
Gout
Other namesArthritis uratica, or Podagra when of the foot
Video summary (script). Leading with The Gout (James Gillray, 1799), which depicts the pain of the artist's gout as a demon or dragon.[1][2]
SpecialtyRheumatology
SymptomsJoint pain, swelling, and redness[3]
Usual onsetOlder males,[3] post-menopausal women[4]
CausesUric acid[4]
Risk factorsDiet high in meat or beer, being overweight, Genetics[3][5]
Differential diagnosisJoint infection, rheumatoid arthritis, pseudogout, others[6]
PreventionWeight loss, abstinence from drinking alcohol, allopurinol[7]
TreatmentNSAIDs, glucocorticoids, colchicine[4][8]
Frequency1–2% (developed world)[7]

Gout (/ɡt/ GOWT[9]) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint,[10][4] caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals.[11] Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours.[7] The joint at the base of the big toe is affected (Podagra) in about half of cases.[12][13] It may also result in tophi, kidney stones, or kidney damage.[3]

Gout is due to persistently elevated levels of uric acid (urate) in the blood (hyperuricemia).[4][7] This occurs from a combination of diet, other health problems, and genetic factors.[3][4] At high levels, uric acid crystallizes and the crystals deposit in joints, tendons, and surrounding tissues, resulting in an attack of gout.[3] Gout occurs more commonly in those who regularly drink beer or sugar-sweetened beverages; eat foods that are high in purines such as liver, shellfish, or anchovies; or are overweight.[3][5] Diagnosis of gout may be confirmed by the presence of crystals in the joint fluid or in a deposit outside the joint.[3] Blood uric acid levels may be normal during an attack.[3]

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or colchicine improves symptoms.[3][4][14] Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention.[7] Taking vitamin C and eating a diet high in low-fat dairy products may be preventive.[15][16]

Gout affects about 1 to 2% of adults in the developed world at some point in their lives.[7] It has become more common in recent decades.[3] This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy, and changes in diet.[7] Older males are most commonly affected.[3] Gout was historically known as "the disease of kings" or "rich man's disease".[7][17] It has been recognized at least since the time of the ancient Egyptians.[7]

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Inflammatory arthritis

Inflammatory arthritis

Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE).

Joint effusion

Joint effusion

A joint effusion is the presence of increased intra-articular fluid. It may affect any joint. Commonly it involves the knee.

Tophus

Tophus

A tophus is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid (urate) in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.

Hyperuricemia

Hyperuricemia

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Tendon

Tendon

A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability to withstand significant amounts of tension.

Purine

Purine

Purine is a heterocyclic aromatic organic compound that consists of two rings fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature.

Synovial joint

Synovial joint

A synovial joint, also known as diarthrosis, joins bones or cartilage with a fibrous joint capsule that is continuous with the periosteum of the joined bones, constitutes the outer boundary of a synovial cavity, and surrounds the bones' articulating surfaces. This joint unites long bones and permits free bone movement and greater mobility. The synovial cavity/joint is filled with synovial fluid. The joint capsule is made up of an outer layer of fibrous membrane, which keeps the bones together structurally, and an inner layer, the synovial membrane, which seals in the synovial fluid.

Glucocorticoid

Glucocorticoid

Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure.

Colchicine

Colchicine

Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken by mouth.

Allopurinol

Allopurinol

Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth or injected into a vein.

Probenecid

Probenecid

Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.

Metabolic syndrome

Metabolic syndrome

Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).

Signs and symptoms

Gout presenting as slight redness in the metatarsophalangeal joint of the big toe
Gout presenting as slight redness in the metatarsophalangeal joint of the big toe

Gout can present in several ways, although the most common is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint).[6] The metatarsophalangeal joint at the base of the big toe is affected most often, accounting for half of cases.[12] Other joints, such as the heels, knees, wrists, and fingers, may also be affected.[6] Joint pain usually begins during the night and peaks within 24 hours of onset.[6] This is mainly due to lower body temperature.[3] Other symptoms may rarely occur along with the joint pain, including fatigue and a high fever.[12][18]

Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion.[19] Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.[20]

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Inflammatory arthritis

Inflammatory arthritis

Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE).

Uric acid

Uric acid

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

Hyperuricemia

Hyperuricemia

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Arthritis

Arthritis

Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.

Kidney

Kidney

The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about 12 centimetres in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.

Acute uric acid nephropathy

Acute uric acid nephropathy

Acute uric acid nephropathy is a rapidly worsening (decreasing) kidney function that is caused by high levels of uric acid in the urine (hyperuricosuria).

Cause

Black-and-white photograph of the arms and hands of a 50-year-old man, showing large tophi of sodium urate affecting the elbow, knuckles, and finger joints.
Black-and-white photograph of the arms and hands of a 50-year-old man, showing large tophi of sodium urate affecting the elbow, knuckles, and finger joints.

The crystallization of uric acid, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate, the salts of uric acid.[3] Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%.[7] About 10% of people with hyperuricemia develop gout at some point in their lifetimes.[21] The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dl), the risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year.[18]

Lifestyle

Dietary causes account for about 12% of gout,[22] and include a strong association with the consumption of alcohol, sugar-sweetened beverages,[23] meat, and seafood.[6] Among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast.[24] Chicken and potatoes also appear related.[25] Other triggers include physical trauma and surgery.[7]

Studies in the early 2000s found that other dietary factors are not relevant.[26][27] Specifically, a diet with moderate purine-rich vegetables (e.g., beans, peas, lentils, and spinach) is not associated with gout.[28] Neither is total dietary protein.[27][28] Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or spirits.[28][29] Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea.[30]

Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout;[31][32][33][34] however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout.[3] Peanuts, brown bread, and fruit also appear protective.[25] This is believed to be partly due to their effect in reducing insulin resistance.[33]

Other than dietary and lifestyle choices, the recurrence of gout attacks is also linked to the weather. High ambient temperature and low relative humidity may increase the risk of a gout attack.[35]

Genetics

Gout is partly genetic, contributing to about 60% of variability in uric acid level.[7] The SLC2A9, SLC22A12, and ABCG2 genes have been found to be commonly associated with gout and variations in them can approximately double the risk.[36][37] Loss-of-function mutations in SLC2A9 and SLC22A12 causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion.[37] The rare genetic disorders familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch–Nyhan syndrome, are complicated by gout.[7]

Medical conditions

Gout frequently occurs in combination with other medical problems. Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance, and abnormal lipid levels, occurs in nearly 75% of cases.[12] Other conditions commonly complicated by gout include lead poisoning, kidney failure, hemolytic anemia, psoriasis, solid organ transplants, and myeloproliferative disorders such as polycythemia.[7][38] A body mass index greater than or equal to 35 increases male risk of gout threefold.[26] Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.[39]

Medication

Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk.[40] Other medications that increase the risk include niacin, aspirin (acetylsalicylic acid), ACE inhibitors, angiotensin receptor blockers, beta blockers, ritonavir, and pyrazinamide.[3][19] The immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout,[7] the former more so when used in combination with hydrochlorothiazide.[41] Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P [42]

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Tophus

Tophus

A tophus is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid (urate) in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.

Crystallization

Crystallization

Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely deposition directly from a gas. Attributes of the resulting crystal depend largely on factors such as temperature, air pressure, and in the case of liquid crystals, time of fluid evaporation.

Uric acid

Uric acid

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

Hyperuricemia

Hyperuricemia

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Anchovy

Anchovy

An anchovy is a small, common forage fish of the family Engraulidae. Most species are found in marine waters, but several will enter brackish water, and some in South America are restricted to fresh water.

Edible mushroom

Edible mushroom

Edible mushrooms are the fleshy and edible fruit bodies of several species of macrofungi. They can appear either below ground (hypogeous) or above ground (epigeous) where they may be picked by hand. Edibility may be defined by criteria that include absence of poisonous effects on humans and desirable taste and aroma. Edible mushrooms are consumed for their nutritional and culinary value. Mushrooms, especially dried shiitake, are sources of umami flavor.

Edible seaweed

Edible seaweed

Edible seaweed, or sea vegetables, are seaweeds that can be eaten and used for culinary purposes. They typically contain high amounts of fiber. They may belong to one of several groups of multicellular algae: the red algae, green algae, and brown algae. Seaweeds are also harvested or cultivated for the extraction of polysaccharides such as alginate, agar and carrageenan, gelatinous substances collectively known as hydrocolloids or phycocolloids. Hydrocolloids have attained commercial significance, especially in food production as food additives. The food industry exploits the gelling, water-retention, emulsifying and other physical properties of these hydrocolloids.

Spinach

Spinach

Spinach is a leafy green flowering plant native to central and western Asia. It is of the order Caryophyllales, family Amaranthaceae, subfamily Chenopodioideae. Its leaves are a common edible vegetable consumed either fresh, or after storage using preservation techniques by canning, freezing, or dehydration. It may be eaten cooked or raw, and the taste differs considerably; the high oxalate content may be reduced by steaming.

Protein toxicity

Protein toxicity

Protein toxicity is the effect of the buildup of protein metabolic waste compounds, like urea, uric acid, ammonia, and creatinine. Protein toxicity has many causes, including urea cycle disorders, genetic mutations, excessive protein intake, and insufficient kidney function, such as chronic kidney disease and acute kidney injury. Symptoms of protein toxicity include unexplained vomiting and loss of appetite. Untreated protein toxicity can lead to serious complications such as seizures, encephalopathy, further kidney damage, and even death.

Insulin resistance

Insulin resistance

Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

Pathophysiology

Chemical structure of uric acid
Chemical structure of uric acid

Gout is a disorder of purine metabolism,[7] and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues.[19] Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation.[43] Naked crystals may break out of walled-off tophi due to minor physical damage to the joint, medical or surgical stress, or rapid changes in uric acid levels.[43] When they break through the tophi, they trigger a local immune-mediated inflammatory reaction in macrophages, which is initiated by the NLRP3 inflammasome protein complex.[3][19][43] Activation of the NLRP3 inflammasome recruits the enzyme caspase 1, which converts pro-interleukin 1β into active interleukin 1β, one of the key proteins in the inflammatory cascade.[3] An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common.[7]

The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase.[19][44] Other triggers believed to be important in acute episodes of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration and extracellular matrix proteins.[7][45][46] The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected.[22] Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy and diuretics.[18] The starting or increasing of urate-lowering medications can lead to an acute attack of gout with febuxostat of a particularly high risk.[47] Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension.[48]

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Precipitation (chemistry)

Precipitation (chemistry)

In an aqueous solution, precipitation is the process of transforming a dissolved substance into an insoluble solid from a super-saturated solution. The solid formed is called the precipitate. In case of an inorganic chemical reaction leading to precipitation, the chemical reagent causing the solid to form is called the precipitant.

Inflammation

Inflammation

Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

NLRP3

NLRP3

NLR family pyrin domain containing 3 (NLRP3), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.

Inflammasome

Inflammasome

Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as cleavage of Gasdermin-D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane.

Caspase 1

Caspase 1

Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.

Primate

Primate

Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians. Primates arose 85–55 million years ago first from small terrestrial mammals, which adapted to living in the trees of tropical forests: many primate characteristics represent adaptations to life in this challenging environment, including large brains, visual acuity, color vision, a shoulder girdle allowing a large degree of movement in the shoulder joint, and dextrous hands. Primates range in size from Madame Berthe's mouse lemur, which weighs 30 g (1 oz), to the eastern gorilla, weighing over 200 kg (440 lb). There are 376–524 species of living primates, depending on which classification is used. New primate species continue to be discovered: over 25 species were described in the 2000s, 36 in the 2010s, and three in the 2020s.

Acidosis

Acidosis

Acidosis is a process causing increased acidity in the blood and other body tissues. If not further qualified, it usually refers to acidity of the blood plasma.

Extracellular matrix

Extracellular matrix

In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

Chemotherapy

Chemotherapy

Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.

Febuxostat

Febuxostat

Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth.

Calcium channel blocker

Calcium channel blocker

Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.

Losartan

Losartan

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

Diagnosis

Synovial fluid examination[49][50]
Type WBC (per mm3) % neutrophils Viscosity Appearance
Normal 0 High Transparent
Osteoarthritis High Clear yellow
Trauma Variable Bloody
Inflammatory 2,000–50,000 50–80 Low Cloudy yellow
Septic arthritis >50,000 >75 Low Cloudy yellow
Gonorrhea ~10,000 60 Low Cloudy yellow
Tuberculosis ~20,000 70 Low Cloudy yellow
Inflammatory: gout, rheumatoid arthritis, rheumatic fever

Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done if the diagnosis is in doubt.[18][51] Plain X-rays are usually normal and are not useful for confirming a diagnosis of early gout.[7] They may show signs of chronic gout such as bone erosion.[47]

Synovial fluid

A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus.[6] All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis should be examined for these crystals.[7] Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence. This test is difficult to perform and requires a trained observer.[52] The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility.[7]

Blood tests

Hyperuricemia is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout.[12][53] Thus, the diagnostic utility of measuring uric acid levels is limited.[12] Hyperuricemia is defined as a plasma urate level greater than 420 μmol/L (7.0 mg/dl) in males and 360 μmol/L (6.0 mg/dl) in females.[54] Other blood tests commonly performed are white blood cell count, electrolytes, kidney function and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection.[55][56] A white blood cell count as high as 40.0×109/l (40,000/mm3) has been documented.[18]

Differential diagnosis

The most important differential diagnosis in gout is septic arthritis.[7][12] This should be considered in those with signs of infection or those who do not improve with treatment.[12] To help with diagnosis, a synovial fluid Gram stain and culture may be performed.[12] Other conditions that can look similar include CPPD (pseudogout), rheumatoid arthritis, psoriatic arthritis, palindromic rheumatism, and reactive arthritis.[3][12] Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell carcinoma[57] or other neoplasms.[58]

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Osteoarthritis

Osteoarthritis

Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the world. The most common symptoms are joint pain and stiffness. Usually the symptoms progress slowly over years. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs, the knee and hip joints, and the joints of the neck and lower back. The symptoms can interfere with work and normal daily activities. Unlike some other types of arthritis, only the joints, not internal organs, are affected.

Hemarthrosis

Hemarthrosis

Hemarthrosis is a bleeding into joint spaces. It is a common feature of hemophilia.

Septic arthritis

Septic arthritis

Acute septic arthritis, infectious arthritis, suppurative arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, heat and pain in a single joint associated with a decreased ability to move the joint. Onset is usually rapid. Other symptoms may include fever, weakness and headache. Occasionally, more than one joint may be involved, especially in neonates, younger children and immunocompromised individuals. In neonates, infants during the first year of life, and toddlers, the signs and symptoms of septic arthritis can be deceptive and mimic other infectious and non-infectious disorders.

Gonorrhea

Gonorrhea

Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with urination, discharge from the penis, or testicular pain. Infected women may experience burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. Many of those infected, however, have no symptoms. If untreated, gonorrhea can spread to joints or heart valves.

Rheumatoid arthritis

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

Rheumatic fever

Rheumatic fever

Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful joints, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of the cases. Damage to the heart valves, known as rheumatic heart disease (RHD), usually occurs after repeated attacks but can sometimes occur after one. The damaged valves may result in heart failure, atrial fibrillation and infection of the valves.

Arthrocentesis

Arthrocentesis

Arthrocentesis, or joint aspiration, is the clinical procedure performed to diagnose and, in some cases, treat musculoskeletal conditions. The procedure entails using a syringe to collect synovial fluid from or inject medication into the joint capsule. Laboratory analysis of synovial fluid can further help characterize the diseased joint and distinguish between gout, arthritis, and synovial infections such as septic arthritis.

Birefringence

Birefringence

Birefringence is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are said to be birefringent. The birefringence is often quantified as the maximum difference between refractive indices exhibited by the material. Crystals with non-cubic crystal structures are often birefringent, as are plastics under mechanical stress.

Hyperuricemia

Hyperuricemia

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Blood plasma

Blood plasma

Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid. It is mostly water, and contains important dissolved proteins, glucose, clotting factors, electrolytes, hormones, carbon dioxide, and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders.

Electrolyte

Electrolyte

An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dissolving, the substance separates into cations and anions, which disperse uniformly throughout the solvent. Solid-state electrolytes also exist. In medicine and sometimes in chemistry, the term electrolyte refers to the substance that is dissolved.

Erythrocyte sedimentation rate

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. To perform the test, anticoagulated blood is traditionally placed in an upright tube, known as a Westergren tube, and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour.

Prevention

Risk of gout attacks can be lowered by complete abstinence from drinking alcoholic beverages, reducing the intake of fructose (e.g. high fructose corn syrup)[60] and purine-rich foods of animal origin, such as organ meats and seafood.[5] Eating dairy products, vitamin C-rich foods, coffee, and cherries may help prevent gout attacks, as does losing weight.[5][61] Gout may be secondary to sleep apnea via the release of purines from oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks.[62]

Medications

As of 2020, allopurinol is generally the recommended preventative treatment if medications are used.[63][64] A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid, febuxostat, benzbromarone, and colchicine.[14][65][66] Long term medications are not recommended until a person has had two attacks of gout,[22] unless destructive joint changes, tophi, or urate nephropathy exist.[20] It is not until this point that medications are cost-effective.[22] They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.[22] They are often used in combination with either an NSAID or colchicine for the first three to six months.[7][14]

While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/L (5.0–6.0 mg/dl),[63][67] there is little evidence to support this practice over simple putting people on a standard dose of allopurinol.[68] If these medications are in chronic use at the time of an attack, it is recommended that they be continued.[12] Levels that cannot be brought below 6.0 mg/dl while attacks continue indicates refractory gout.[69]

While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable.[70] Allopurinol blocks uric acid production, and is the most commonly used agent.[22] Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.[22] The HLA-B*58:01 allele of the human leukocyte antigen B (HLA-B) is strongly associated with severe cutaneous adverse reactions during treatment with allopurinol and is most common among Asian subpopulations, notably those of Korean, Han-Chinese, or Thai descent.[71]

Febuxostat is only recommended in those who cannot tolerate allopurinol.[72] There are concerns about more deaths with febuxostat compared to allopurinol.[73] Febuxostat may also increase the rate of gout flares during early treatment.[74] However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol.[75]

Probenecid appears to be less effective than allopurinol and is a second line agent.[22][65] Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800 mg).[76] It is, however, not recommended if a person has a history of kidney stones.[76] Pegloticase is an option for the 3% of people who are intolerant to other medications.[77] It is a third line agent.[65] Pegloticase is given as an intravenous infusion every two weeks,[77] and reduces uric acid levels.[78] Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it.[65] Using lesinurad 400 mg plus febuxostat is more beneficial for tophi resolution than lesinural 200 mL with febuxostat, with similar side effects. Lesinural plus allopurinol is not effective for tophi resolution.[79] Potential side effects include kidney stones, anemia and joint pain.[80] In 2016, it was withdrawn from the European market.[81][82]

Lesinurad reduces blood uric acid levels by preventing uric acid absorption in the kidneys.[83] It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets.[84] Side effects include kidney problems and kidney stones.[83][85]

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Alcohol (drug)

Alcohol (drug)

Alcohol, sometimes referred to by the chemical name ethanol, is a depressant drug that is the active ingredient in drinks such as beer, wine, and distilled spirits. It is one of the oldest and most commonly consumed recreational drugs, causing the characteristic effects of alcohol intoxication ("drunkenness"). Among other effects, alcohol produces happiness and euphoria, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor, and sensory function, and generalized depression of central nervous system (CNS) function. Ethanol is only one of several types of alcohol, but it is the only type of alcohol that is found in alcoholic beverages or commonly used for recreational purposes; other alcohols such as methanol and isopropyl alcohol are significantly more toxic. A mild, brief exposure to isopropanol, being only moderately more toxic than ethanol, is unlikely to cause any serious harm. Methanol, being profoundly more toxic than ethanol, is lethal in quantities as small as 10–15 milliliters.

Fructose

Fructose

Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed by the gut directly into the blood of the portal vein during digestion. The liver then converts both fructose and galactose into glucose, so that dissolved glucose, known as blood sugar, is the only monosaccharide present in circulating blood.

Dairy product

Dairy product

Dairy products or milk products, also known as lacticinia, are food products made from milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in the Western world such as yogurt, cheese and butter. A facility that produces dairy products is known as a dairy. Dairy products are consumed worldwide to varying degrees. Some people avoid some or all dairy products either because of lactose intolerance, veganism, or other health reasons or beliefs.

Coffee

Coffee

Coffee is a beverage prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content. It has the highest sales in the world market for hot drinks.

Cherry

Cherry

A cherry is the fruit of many plants of the genus Prunus, and is a fleshy drupe.

Allopurinol

Allopurinol

Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth or injected into a vein.

Febuxostat

Febuxostat

Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth.

Benzbromarone

Benzbromarone

Benzbromarone is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone.

Acute uric acid nephropathy

Acute uric acid nephropathy

Acute uric acid nephropathy is a rapidly worsening (decreasing) kidney function that is caused by high levels of uric acid in the urine (hyperuricosuria).

HLA-B58

HLA-B58

HLA-B58 (B58) is an HLA-B serotype. B58 is a split antigen from the B17 broad antigen, the sister serotype B57. The serotype identifies the more common HLA-B*58 gene products. B*5801 is associated with allopurinol induced inflammatory necrotic skin disease.

Human leukocyte antigen

Human leukocyte antigen

The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

HLA-B

HLA-B

HLA-B is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.

Treatment

The initial aim of treatment is to settle the symptoms of an acute attack.[86] Repeated attacks can be prevented by medications that reduce serum uric acid levels.[86] Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.[87] Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids.[22] While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer.[88] Options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease.[7] Treatment of associated health problems is also important.[7] Lifestyle interventions have been poorly studied.[87] It is unclear whether dietary supplements have an effect in people with gout.[89]

NSAIDs

NSAIDs are the usual first-line treatment for gout. No specific agent is significantly more or less effective than any other.[22] Improvement may be seen within four hours and treatment is recommended for one to two weeks.[7][22] They are not recommended for those with certain other health problems, such as gastrointestinal bleeding, kidney failure, or heart failure.[90] While indometacin has historically been the most commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness.[40] For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.[91] There is some evidence that COX-2 inhibitors may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.[92][93]

Colchicine

Colchicine is an alternative for those unable to tolerate NSAIDs.[22] At high doses, side effects (primarily gastrointestinal upset) limit its usage.[94] At lower doses, which are still effective, it is well tolerated.[40][95] Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.[94]

Glucocorticoids

Glucocorticoids have been found to be as effective as NSAIDs[96][93] and may be used if contraindications exist for NSAIDs.[22][97] They also lead to improvement when injected into the joint.[22] A joint infection must be excluded, however, as glucocorticoids worsen this condition.[22] There were no short-term adverse effects reported.[98]

Others

Interleukin-1 inhibitors, such as canakinumab, showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of adverse events, such as back pain, headache, and increased blood pressure.[99] They, however, may work less well than usual doses of NSAIDS.[99] The high cost of this class of drugs may also discourage their use for treating gout.[99]

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Colchicine

Colchicine

Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken by mouth.

Glucocorticoid

Glucocorticoid

Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure.

Allopurinol

Allopurinol

Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth or injected into a vein.

Febuxostat

Febuxostat

Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth.

Comorbidity

Comorbidity

In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity - is the presence of one or more additional conditions often co-occurring with a primary condition. Comorbidity describes the effect of all other conditions an individual patient might have other than the primary condition of interest, and can be physiological or psychological. In the context of mental health, comorbidity often refers to disorders that are often coexistent with each other, such as depression and anxiety disorders. The concept of multimorbidity is related to comorbidity but presents a different meaning and approach.

Gastrointestinal bleeding

Gastrointestinal bleeding

Gastrointestinal bleeding, also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include vomiting red blood, vomiting black blood, bloody stool, or black stool. Small amounts of bleeding over a long time may cause iron-deficiency anemia resulting in feeling tired or heart-related chest pain. Other symptoms may include abdominal pain, shortness of breath, pale skin, or passing out. Sometimes in those with small amounts of bleeding no symptoms may be present.

Heart failure

Heart failure

Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms, caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is measured by the severity of symptoms during exercise. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease.

Indometacin

Indometacin

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.

Ibuprofen

Ibuprofen

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins working within an hour.

COX-2 inhibitor

COX-2 inhibitor

COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.

Atorvastatin

Atorvastatin

Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.

Erythromycin

Erythromycin

Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used during pregnancy to prevent Group B streptococcal infection in the newborn, as well as to improve delayed stomach emptying. It can be given intravenously and by mouth. An eye ointment is routinely recommended after delivery to prevent eye infections in the newborn.

Prognosis

Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.[18] Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and kidney and cardiovascular disease and thus are at increased risk of death.[7][100] It is unclear whether medications that lower urate affect cardiovascular disease risks.[101] This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.[100]

Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi.[7] These tophi occur in 30% of those who are untreated for five years, often in the helix of the ear, over the olecranon processes, or on the Achilles tendons.[7] With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH promoting the precipitation of uric acid.[7] Other forms of chronic kidney dysfunction may occur.[7]

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Hypertension

Hypertension

Hypertension, also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high blood pressure, however, is a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide.

Metabolic syndrome

Metabolic syndrome

Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).

Cardiovascular disease

Cardiovascular disease

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases, stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

Insulin resistance

Insulin resistance

Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

Helix (ear)

Helix (ear)

The helix is the prominent rim of the auricle. Where the helix turns downwards posteriorly, a small tubercle is sometimes seen, namely the auricular tubercle of Darwin.

Olecranon

Olecranon

The olecranon, is a large, thick, curved bony eminence of the ulna, a long bone in the forearm that projects behind the elbow. It forms the most pointed portion of the elbow and is opposite to the cubital fossa or elbow pit. The olecranon serves as a lever for the extensor muscles that straighten the elbow joint.

Kidney failure

Kidney failure

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, high blood potassium, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anemia.

Tophus

Tophus

A tophus is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid (urate) in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.

Gross pathology

Gross pathology

Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.

Epidemiology

Gout affects around 1–2% of people in the Western world at some point in their lifetimes and is becoming more common.[7][22] Some 5.8 million people were affected in 2013.[102] Rates of gout approximately doubled between 1990 and 2010.[19] This rise is believed to be due to increasing life expectancy, changes in diet and an increase in diseases associated with gout, such as metabolic syndrome and high blood pressure.[26] Factors that influence rates of gout include age, race, and the season of the year. In men over 30 and women over 50, rates are 2%.[90]

In the United States, gout is twice as likely in males of African descent than those of European descent.[103] Rates are high among Pacific Islanders and the Māori, but the disease is rare in aboriginal Australians, despite a higher mean uric acid serum concentration in the latter group.[104] It has become common in China, Polynesia, and urban Sub-Saharan Africa.[7] Some studies found that attacks of gout occur more frequently in the spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity, and temperature.[105]

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Western world

Western world

The Western world, also known as the West, primarily refers to various nations and states in the regions of Australasia, Europe, and the Americas. The Western world likewise is called the Occident, in contrast to the Eastern world known as the Orient. The West is considered an evolving concept; made up of cultural, political, and economic synergy among diverse groups of people, and not a rigid region with fixed borders and members. Definitions for "Western world" vary according to context and perspectives.

United States

United States

The United States of America, commonly known as the United States or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territories, nine Minor Outlying Islands, and 326 Indian reservations. The United States is also in free association with three Pacific Island sovereign states: the Federated States of Micronesia, the Marshall Islands, and the Republic of Palau. It is the world's third-largest country by both land and total area. It shares land borders with Canada to its north and with Mexico to its south and has maritime borders with the Bahamas, Cuba, Russia, and other nations. With a population of over 333 million, it is the most populous country in the Americas and the third most populous in the world. The national capital of the United States is Washington, D.C. and its most populous city and principal financial center is New York City.

Māori people

Māori people

Māori are the indigenous Polynesian people of mainland New Zealand. Māori originated with settlers from East Polynesia, who arrived in New Zealand in several waves of canoe voyages between roughly 1320 and 1350. Over several centuries in isolation, these settlers developed their own distinctive culture, whose language, mythology, crafts, and performing arts evolved independently from those of other eastern Polynesian cultures. Some early Māori moved to the Chatham Islands, where their descendants became New Zealand's other indigenous Polynesian ethnic group, the Moriori.

Aboriginal Australians

Aboriginal Australians

Aboriginal Australians are the various Indigenous peoples of the Australian mainland and many of its islands, such as the peoples of Tasmania, Fraser Island, Hinchinbrook Island, the Tiwi Islands, and Groote Eylandt, but excluding the Torres Strait Islands. The term Indigenous Australians refers to Aboriginal Australians and Torres Strait Islanders collectively. It is generally used when both groups are being discussed. Torres Strait Islanders are ethnically and culturally distinct, despite extensive cultural exchange with some of the Aboriginal groups. The Torres Strait Islands are mostly part of Queensland but have a separate governmental status.

China

China

China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and borders fourteen countries by land, the most of any country in the world, tied with Russia. With an area of approximately 9.6 million square kilometres (3,700,000 sq mi), it is the world's third largest country by total land area. The country consists of 22 provinces, five autonomous regions, four municipalities, and two special administrative regions. The national capital is Beijing, and the most populous city and largest financial center is Shanghai.

Polynesia

Polynesia

Polynesia is a subregion of Oceania, made up of more than 1,000 islands scattered over the central and southern Pacific Ocean. The indigenous people who inhabit the islands of Polynesia are called Polynesians. They have many things in common, including language relatedness, cultural practices, and traditional beliefs. In centuries past, they had a strong shared tradition of sailing and using stars to navigate at night. The largest country in Polynesia is New Zealand.

Sub-Saharan Africa

Sub-Saharan Africa

Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the African countries and territories that are situated fully in that specified region, the term may also include polities that only have part of their territory located in that region, per the definition of the United Nations (UN). This is considered a non-standardized geographical region with the number of countries included varying from 46 to 48 depending on the organization describing the region. The African Union (AU) uses a different regional breakdown, recognizing all 55 member states on the continent - grouping them into 5 distinct and standard regions.

History

Antonie van Leeuwenhoek described the microscopic appearance of uric acid crystals in 1679.[106]
Antonie van Leeuwenhoek described the microscopic appearance of uric acid crystals in 1679.[106]

The term "gout" was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word gutta, meaning "a drop" (of liquid).[106] According to the Oxford English Dictionary, this is derived from humorism and "the notion of the 'dropping' of a morbid material from the blood in and around the joints".[107]

Gout has been known since antiquity. Historically, it was referred to as "the king of diseases and the disease of kings"[7][108] or "rich man's disease".[17] The Ebers papyrus and the Edwin Smith papyrus, (c. 1550 BC) each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier by Imhotep.[109] Greek physician Hippocrates around 400 BC commented on it in his Aphorisms, noting its absence in eunuchs and premenopausal women.[106][110] Aulus Cornelius Celsus (30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:

Again thick urine, the sediment from which is white, indicates that pain and disease are to be apprehended in the region of joints or viscera... Joint troubles in the hands and feet are very frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack eunuchs or boys before coition with a woman, or women except those in whom the menses have become suppressed... some have obtained lifelong security by refraining from wine, mead and venery.[111]

Benjamin Welles, an English physician authored the first medical book on gout, A Treatise of the Gout, or Joint Evil, in 1669.[112] In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of the morning and its predilection for older males:

Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age—of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever... The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on.[113]

Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679.[106] In 1848, English physician Alfred Baring Garrod identified excess uric acid in the blood as the cause of gout.[114]

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Antonie van Leeuwenhoek

Antonie van Leeuwenhoek

Antonie Philips van Leeuwenhoek was a Dutch microbiologist and microscopist in the Golden Age of Dutch science and technology. A largely self-taught man in science, he is commonly known as "the Father of Microbiology", and one of the first microscopists and microbiologists. Van Leeuwenhoek is best known for his pioneering work in microscopy and for his contributions toward the establishment of microbiology as a scientific discipline.

Oxford English Dictionary

Oxford English Dictionary

The Oxford English Dictionary (OED) is the principal historical dictionary of the English language, published by Oxford University Press (OUP). It traces the historical development of the English language, providing a comprehensive resource to scholars and academic researchers, as well as describing usage in its many variations throughout the world.

Humorism

Humorism

Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek and Roman physicians and philosophers.

Imhotep

Imhotep

Imhotep was an Egyptian chancellor to the Pharaoh Djoser, possible architect of Djoser's step pyramid, and high priest of the sun god Ra at Heliopolis. Very little is known of Imhotep as a historical figure, but in the 3,000 years following his death, he was gradually glorified and deified.

Ancient Greece

Ancient Greece

Ancient Greece was a northeastern Mediterranean civilization, existing from the Greek Dark Ages of the 12th–9th centuries BC to the end of classical antiquity, that comprised a loose collection of culturally and linguistically related city-states and other territories. Most of these regions were officially unified only once, for 13 years, under Alexander the Great's empire from 336 to 323 BC. In Western history, the era of classical antiquity was immediately followed by the Early Middle Ages and the Byzantine period.

Hippocrates

Hippocrates

Hippocrates of Kos, also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referred to as the "Father of Medicine" in recognition of his lasting contributions to the field, such as the use of prognosis and clinical observation, the systematic categorization of diseases, or the formulation of humoral theory. The Hippocratic school of medicine revolutionized ancient Greek medicine, establishing it as a discipline distinct from other fields with which it had traditionally been associated, thus establishing medicine as a profession.

Aulus Cornelius Celsus

Aulus Cornelius Celsus

Aulus Cornelius Celsus was a Roman encyclopaedist, known for his extant medical work, De Medicina, which is believed to be the only surviving section of a much larger encyclopedia. The De Medicina is a primary source on diet, pharmacy, surgery and related fields, and it is one of the best sources concerning medical knowledge in the Roman world. The lost portions of his encyclopedia likely included volumes on agriculture, law, rhetoric, and military arts. He made contributions to the classification of human skin disorders in dermatology, such as myrmecia, and his name is often found in medical terminology regarding the skin, e.g., kerion celsi and area celsi.

Eunuch

Eunuch

A eunuch is a male who has been castrated. Throughout history, castration often served a specific social function.

Wine

Wine

Wine is an alcoholic drink typically made from fermented grapes. Yeast consumes the sugar in the grapes and converts it to ethanol and carbon dioxide, releasing heat in the process. Different varieties of grapes and strains of yeasts are major factors in different styles of wine. These differences result from the complex interactions between the biochemical development of the grape, the reactions involved in fermentation, the grape's growing environment (terroir), and the wine production process. Many countries enact legal appellations intended to define styles and qualities of wine. These typically restrict the geographical origin and permitted varieties of grapes, as well as other aspects of wine production. Wines can be made by fermentation of other fruit crops such as plum, cherry, pomegranate, blueberry, currant and elderberry.

Mead

Mead

Mead, also called hydromel, particularly when low in alcohol content, is an alcoholic beverage made by fermenting honey mixed with water, and sometimes with added ingredients such as fruits, spices, grains, or hops. The alcoholic content ranges from about 3.5% ABV to more than 20%. The defining characteristic of mead is that the majority of the beverage's fermentable sugar is derived from honey. It may be still, carbonated, or naturally sparkling; dry, semi-sweet, or sweet.

Thomas Sydenham

Thomas Sydenham

Thomas Sydenham was an English physician. He was the author of Observationes Medicae which became a standard textbook of medicine for two centuries so that he became known as 'The English Hippocrates'. Among his many achievements was the discovery of a disease, Sydenham's chorea, also known as St Vitus' Dance. To him is attributed the prescient dictum, "A man is as old as his arteries."

Alfred Baring Garrod

Alfred Baring Garrod

Sir Alfred Baring Garrod was an English physician.

Other animals

Gout is rare in most other animals due to their ability to produce uricase, which breaks down uric acid.[115] Humans and other great apes do not have this ability; thus, gout is common.[18][115] Other animals with uricase include fish, amphibians and most non-primate mammals.[116] The Tyrannosaurus rex specimen known as "Sue" is believed to have had gout.[117]

Research

A number of new medications are under study for treating gout, including anakinra, canakinumab, and rilonacept.[118] Canakinumab may result in better outcomes than a low dose of a glucocorticoid, but costs five thousand times more.[119] A recombinant uricase enzyme (rasburicase) is available but its use is limited, as it triggers an immune response. Less antigenic versions are in development.[18]

Discover more about Research related topics

Anakinra

Anakinra

Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum. Anakinra is administered by subcutaneous injection.

Canakinumab

Canakinumab

Canakinumab, sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis and active Still's disease, including adult-onset Still's disease. It is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.

Rilonacept

Rilonacept

Rilonacept, sold under the brand name Arcalyst, is a medication used to treat cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome, and Muckle–Wells syndrome; deficiency of interleukin-1 receptor antagonist; and recurrent pericarditis. Rilonacept is an interleukin 1 inhibitor.

Recombinant DNA

Recombinant DNA

Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome.

Rasburicase

Rasburicase

Rasburicase is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.

Source: "Gout", Wikipedia, Wikimedia Foundation, (2023, March 2nd), https://en.wikipedia.org/wiki/Gout.

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