A disturbance of uric-acid metabolism occurring chiefly in males, characterized by painful inflammation of the joints, especially of the feet and hands.
Gout (also known as podagra when it involves the big toe) is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected. However, it may also present itself as tophi, kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.
Diagnosis is confirmed clinically by the visualization of the characteristic crystals in joint fluid. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine, and most importantly medical marijuana improves symptoms. Once the acute attack has subsided, levels of uric acid are usually lowered via lifestyle changes.
Gout has increased in frequency in recent decades affecting approximately one to two percent of the Western population at some point in their lives. The increase is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy and changes in diet. Gout was historically known as "the disease of kings" or "rich man's disease".
Gout can present in a number of ways, although the most usual is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). T he metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases. Other joints, such as the heels, knees, wrists and fingers, may also be affected. Joint pain usually begins over 2–4 hours and during the night. The reason for onset at night is due to the lower body temperature then. Other symptoms that may occur along with the joint pain include fatigue and a high fever.
Long-standing elevated uric acid levels (hyperuricemia) may result in other symptomatology, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.
Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons, including diet, genetic predisposition, or under excretion of urate, the salts of uric acid. Renal under excretion of uric acid is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%. About 10% of people with hyperuricemia develop gout at some point in their lifetimes. The risk, however, varies depending on the degree of hyperuricemia.
Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggers include physical trauma and surgery. Recent studies have found dietary factors once believed to be associated are in fact not, including the intake of purine-rich vegetables and total protein. The consumption of coffee, vitamin C and dairy products as well as physical fitness appear to decrease the risk. This is believed to be partly due to their effect in reducing insulin resistance.
The occurrence of gout is genetic, contributing to about 60% of variability in uric acid level. A few rare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase super activity, and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.
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. Other conditions which are commonly complicated by gout include:polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis, and solid organ transplants. A body mass index greater than or equal to 35 increases a male's risk of gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function. Lesch-Nyhan syndrome is often associated with gouty arthritis.
Without treatment, an acute attack of gout will usually resolve in 5 to 7 days. However, 60% of people will have a second attack within one year. Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease and thus at increased risk of death. This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.
Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi. 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. 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. Other forms of chronic renal dysfunction may occur.
Gout affects around 1–2% of the Western population at some point in their lifetimes, and is becoming more common. Rates of gout have approximately doubled between 1990 and 2010. 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. A number of factors have been found to influence rates of gout, including age, race, and the season of the year. In men over the age of 30 and women over the age of 50, prevalence is 2%.
In the United States, gout is twice as likely in African American males as it is in European Americans. Rates are high among the peoples of the Pacific Islands and the Maori of New Zealand, but rare in Australian aborigines, despite a higher mean concentration of serum uric acid in the latter group. I t has become common in China, Polynesia, and urban sub-Saharan Africa. Some studies have found attacks of gout occur more frequently in the spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity, and temperature.
Diuretics have been associated with attacks of gout. However, a low dose of hydrochlorothiazide does not seem to increase the risk. Other medicines that have been associated include niacin and aspirin (acetylsalicylic acid). Cyclosporine is also associated with gout, particularly when used in combination with hydrochlorothiazide, as are the immuno-suppressive drugs ciclosporin and tacrolimus.
Both lifestyle changes and medications can decrease uric acid levels. Dietary and lifestyle choices that are effective include reducing intake of food such as meat and seafood, consuming adequate vitamin C, limiting alcohol and fructose consumption, and avoiding obesity. A low-calorie diet in obese men decreased uric acid levels. Vitamin C intake of 1,500 mg per day decreases the risk of gout by 45% compared to 250 mg per day. Coffee, but not tea, consumption is associated with a lower risk of gout. 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.
The initial aim of treatment is to settle the symptoms of an acute attack. Different drugs used to reduce the serum uric acid levels can prevent repeated attacks. Ice applied for 20 to 30 minutes several times a day decreases pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids, while options for prevention include allopurinol, febuxostat and probenecid. Lowering uric acid levels can cure the disease. Treatment of co morbidities is also important.
NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly more or less effective than any other is. Improvement may be seen within 4 hours, and treatment is recommended for 1–2 weeks. They are not recommended, however in those with certain other health problems, such as gastrointestinal bleeding, renal failure, or heart failure. While indomethacin 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. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.
Colchicine is an alternative for those unable to tolerate NSAIDs. Its side effects (primarily gastrointestinal upset) limit its usage. Gastrointestinal upset, however, depends on the dose, and the risk can be decreased by using smaller yet still effective doses. Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.
Glucocorticoids have been found to be as effective as NSAIDs and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into the joint; the risk of a joint infection must be excluded, however, as they worsen this condition.
Pegloticase (Krystexxa) was approved in the USA to treat gout in 2010. It will be an option for the 3% of people who are not adequately treated with other medications due to their association with severe allergic reactions. Pegloticase is administered as an intravenous infusion every two weeks. As of March 2010, however, no double blind, placebo controlled trials have been completed.
A number of medications are useful for preventing further episodes of gout, including xanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics (including probenecid and sulfinpyrazone). They are not usually commenced until one to two weeks after an acute attack has resolved, due to theoretical concerns of worsening the attack, and are often used in combination with either an NSAID or colchicine for the first 3–6 months. They are not recommended until a person has suffered two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist, as it is not until this point that medications have been found to be cost effective. Urate-lowering measures should be increased until serum uric acid levels are below (5.0-6.0 mg/dL) and are continued indefinitely. If these medications are being used chronically at the time of an attack, it is recommended they be continued.
As a rule of thumb, uricosuric drugs are preferred if there is under secretion of uric acid, in turn indicated if a 24-hour collection of urine results in a uric acid amount of less than 800mg. They are, however, contraindicated if the person has a history of renal stones. In contrast, a 24-hour urine excretion of more than 800mg indicates overproduction, and xanthine oxidase inhibitors are preferred. Overall, probenecid appears to be less effective than allopurinol.
Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acid production, and long-term therapy is safe and well tolerated, and can be used in people with renal impairment or urate stones, although allopurinol has caused hypersensitivity in a small number of individuals. I n such cases, the alternative drug febuxostat have been recommended.
The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679. In 1848 English physician, Alfred Baring Garrod realized that this excess uric acid in the blood was the cause of gout.
Gout is a disorder of purine metabolism, an nd occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and in the surrounding tissues. These crystals then trigger a local immune-mediated inflammatory reaction with one of the key proteins in the inflammatory cascade being interleukin 1β. An evolutionary loss of uricase, which breaks down uric acid, in humans and higher primates is what has made this condition so common.
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. Other factors believed to be important in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate. The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to a number of factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol.
Gout is rare in most other animals due to their ability to produce uricase, which breaks down uric acid. Humans and other great apes have lost this ability, and thus gout is common. The Tyrannosaurus rex specimen known as "Sue", however, is believed to have suffered from gout.
One of marijuana’s oldest recorded uses is relieving swelling and inflammation. Currently, modern scientists are exploring a network of cannabinoid receptor sites located throughout the body. This new understandings of cannabinoid research clearly supports the historical references on treating inflammation with marijuana. Different cannabinoids founds naturally in marijuana have different benefits for arthritis sufferers. Tetrahydroconnabinol (THC) is beneficial as a pain reliever. Cannabichromene (CBC) and cannabidiol (CBD) have been shown in clinical studies to have valuable anti-inflammatory properties.
Arthritis literally means "joint inflammation". It consists of more than 100 different conditions. The common symptoms for all these conditions are joint and musculoskeletal pain, which is why they are all considered forms of “arthritis'. Often the pain associated with arthritis is a result of inflammation of the joint lining. Inflammation is the body's natural response to injury. The warning signs that inflammation presents are redness, swelling, heat and pain. When a joint becomes inflamed, it can prevent the normal use of the joint and therefore it can cause the loss of function of joint.
Gout is one of the most painful forms of arthritis. Gout is caused when crystals of uric acid form in the connective tissue and/or joint spaces.
Arthritis and Cannabinoids: HU-210 and Win-55, 212-2 Prevent IL-1Alpha-Induced Matrix Degradation in Bovine Articular Chondrocytes In-Vitro.
Mbvundula EC, Bunning RA, Rainsford KD.
Biomedical Research Centre, Sheffield Hallam University, Sheffield, S1 1WB, UK.
Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis. In this study the mechanisms of action of the synthetic cannabinoid agonists, HU-210 and Win-55,212-2, were studied to determine if they affected interleukin-1 alpha (IL-1alpha)-induced proteoglycan and collagen degradation in bovine nasal cartilage explant cultures and prostaglandin E2 (PGE2) production in primary cultures of bovine articular chondrocytes. The effects of the inactive enantiomer, Win-55,212-3, were compared with those of the active enantiomer, Win-55,212-2, to determine if the effects were cannabinoid (CB)-receptor mediated. The chondrocytes and explants were stimulated by IL-1alpha (100 U mL(-1) identical with 0.06 nM and 500 U mL(-1) identical with 0.3 nM, respectively). Proteoglycan breakdown was determined as sulfated glycosaminoglycan (sGAG) release using the dimethylmethylene blue assay. Collagen degradation was determined as hydroxyproline in the conditioned culture media and cartilage digests. ELISA determined PGE2. Expression of cannabinoid receptors, CB1 and CB2; cyclooxygenase-1 and -2 (COX-1 and COX-2); inducible nitric oxide synthase (iNOS); as well as activation of nuclear factor-kappa B (NF-kappaB) in chondrocytes were studied using immunoblotting techniques and immunofluorescence.
The results showed that HU-210 and Win-55,212-2 (5-15 microM) significantly inhibited IL-1-alpha stimulated proteoglycan (P < 0.001) and collagen degradation (P < 0.001). Win-55,212-2 (5-10 microM) also significantly inhibited PGE2 production (P < 0.01). At 5 microM, Win-55,212-2 inhibited the expression of iNOS and COX-2 and activation of NF-kappaB. Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2. It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism. Cannabinoids could also be producing these effects via inhibition of NF-kappaB activation.
Sativex (CBM) is a marijuana-based drug that was developed by GW Pharmaceuticals in 2005 as a treatment for Multiple Sclerosis. Sativex has however been shown to have beneficial effects in rheumatoid arthritis. Tests of Sativex on arthritis patients showed it helped reduce pain, and improve quality of sleep. Sativex is not psychoactive and comes in the form of a mouth spray composed mainly of two cannabinoids found naturally in marijuana, Tetrahydroconnabinol (THC) and cannabidiol (CBD).
Topical application of cannabis extract on cases of arthropathy (gout) were done in So. Calif. Positive test results: less inflammation, less pain than placebo group.
Make your own Cannabis Liniment: Crush 1 oz of Indica shake. Put it into a container and add on top of it 12-16 ozs. Isoprophyl Alcohol (70-90 %). Tightly cover the container and shake vigorously. Then allow mixture to set or steep in the container for 15-30 days. Shake it lightly once everyday. Do not open the container until the 30 days is up. When it is done, open the container and filter the contents to remove any solids. Pour the mixture into a dispensing bottle with a good tight cap. Your liniment is ready to use.
Cannabinoids decrease inflammation by suppressing certain parts of the immune system. You can also take cannabinoids by vaporizing, edibles, as an extract or tincture (under the tongue), or in a suppository form.
1. ^ a b c d e f g h i j Eggebeen AT (September 2007). "Gout: an update”. Am Fam Physician 76 (6): 801–8. PMID 17910294.
2. ^ a b c d e f g h i j k l m n o p q r s Chen LX, Schumacher HR (October 2008). "Gout: an evidence-based review". J Clin Rheumatol 14 (5 Suppl): S55–62. doi:10.1097/RHU.0b013e3181896921.PMID 18830092.
3. ^ a b c d e f g h i j k l m Schlesinger N (March 2010). "Diagnosing and treating gout: a review to aid primary care physicians". Post grad Med122 (2): 157–61. doi:10.3810/pgm.2010.03.2133.PMID 20203467.
4. ^ a b c d e f g Terkeltaub R (January 2010). "Update on gout: new therapeutic strategies and options". Nat Rev Rheumatol 6 (1): 30–8.doi:10.1038/nrrheum.2009.236. PMID 20046204.
5. ^ a b Tausche AK, Jansen TL, Schröder HE, Bornstein SR, Aringer M, Müller-Ladner U (August 2009). "Gout--current diagnosis and treatment". Dtsch Arztebl Int 106 (34-35): 549–55.doi:10.3238/arztebl.2009.0549. PMC 2754667.PMID 19795010.
6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Richette P, Bardin T (January 2010). "Gout". Lancet 375 (9711): 318–28.doi:10.1016/S0140-6736(09)60883-7. PMID 19692116.
7. ^ Vitart V, Rudan I, Hayward C, et al. (April 2008). "SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout". Nat. Genet. 40 (4): 437–42.doi:10.1038/ng.106. PMID 18327257.
8. ^ Weaver, AL (2008 Jul). "Epidemiology of gout.” Cleveland Clinic journal of medicine 75 Suppl 5: S9-12. PMID 18819329.
9. ^ Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G (March 2004). "Purine-rich foods, dairy and protein intake, and the risk of gout in men". N. Engl. J. Med. 350 (11): 1093–103.doi:10.1056/NEJMoa035700. PMID 15014182.
10. ^ a b c Weaver AL (July 2008). "Epidemiology of gout". Cleve Clin J Med 75 Suppl 5: S9–12. PMID 18819329.
11. ^ Hak AE, Choi HK (March 2008). "Lifestyle and gout". Curr Opin Rheumatol 20 (2): 179–86. doi:10.1097/BOR.0b013e3282f524a2.PMID 18349748.
12. ^ Williams PT (May 2008). "Effects of diet, physical activity and performance, and body weight on incident gout in ostensibly healthy, vigorously active men". Am. J. Clin. Nutr. 87 (5): 1480–7.PMID 18469274.
13. ^ a b Choi HK (March 2010). "A prescription for lifestyle change in patients with hyperuricemia and gout". Curr Opin Rheumatol 22 (2): 165–72. doi:10.1097/BOR.0b013e328335ef38. PMID 20035225.
14. ^ Stamp L, Searle M, O'Donnell J, Chapman P (2005). "Gout in solid organ transplantation: a challenging clinical problem". Drugs 65 (18): 2593–611. PMID 16392875.
15. ^ Loghman-Adham M (September 1997). "Renal effects of environmental and occupational lead exposure". Environ. Health Perspect. (Brogan & Partners) 105 (9): 928–38.doi:10.2307/3433873. JSTOR 3433873. PMC 1470371.PMID 9300927.
16. ^ a b c d Laubscher T, Dumont Z, Regier L, Jensen B (December 2009). "Taking the stress out of managing gout". Can Fam Physician55 (12): 1209–12. PMC 2793228. PMID 20008601.
17. ^ Firestein, MD, Shaun; Budd, MD, Ralph C.; Harris Jr., MD, Edward D. et al., eds (2008). "Chapter 87: Gout and Hyperuricemia". KELLEY'S Textbook of Rheumatology (8th ed.). Elsevier. ISBN 978-1-4160-4842-8.
18. ^ Virsaladze DK, Tetradze LO, Dzhavashvili LV, Esaliia NG, Tananashvili DE (May 2007). "[Levels of uric acid in serum in patients with metabolic syndrome] [Levels of uric acid in serum in patients with metabolic syndrome]" (in Russian). Georgian Med News (146): 35–7.PMID 17595458.
19. ^ Moyer RA, John DS (April 2003). "Acute gout precipitated by total parenteral nutrition". The Journal of rheumatology 30 (4): 849–50.PMID 12672211.
20. ^ Halabe A, Sperling O (1994). "Uric acid nephrolithiasis". Mineral and electrolyte metabolism 20 (6): 424–31. PMID 7783706.
21. ^ Schlesinger N (December 2007). "Diagnosis of gout". Minerva Med.98 (6): 759–67. PMID 18299687.
22. ^ Sturrock R (2000). "Gout. Easy to misdiagnose". BMJ 320 (7228): 132–33. doi:10.1136/bmj.320.7228.132. PMC 1128728.PMID 10634714.
23. ^ Sachs L, Batra KL, Zimmermann B (November 2009). "Medical implications of hyperuricemia". Med Health R I 92 (11): 353–55.PMID 19999892.
24. ^ "Gout: Differential Diagnoses & Workup - eMedicine Rheumatology".
25. ^ "Gout and Pseudogout: Differential Diagnoses & Workup - eMedicine Emergency Medicine".
26. ^ Jordan DR, Belliveau MJ, Brownstein S, McEachren T, Kyrollos M (2008). "Medial canthal tophus". Ophthal Plast Reconstr Surg 24 (5): 403–4. doi:10.1097/IOP.0b013e3181837a31. PMID 18806664.
27. ^ Sano K, Kohakura Y, Kimura K, Ozeki S (March 2009). "Atypical Triggering at the Wrist due to Intratendinous Infiltration of Tophaceous Gout". Hand (N Y) 4 (1): 78–80. doi:10.1007/s11552-008-9120-4.PMC 2654956. PMID 18780009.
28. ^ Choi HK, Gao X, Curhan G (March 2009). "Vitamin C intake and the risk of gout in men: a prospective study". Arch. Intern. Med. 169 (5): 502–7. doi:10.1001/archinternmed.2008.606. PMC 2767211.PMID 19273781.
29. ^ Choi HK, Curhan G (June 2007). "Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey". Arthritis Rheum. 57 (5): 816–21.doi:10.1002/art.22762. PMID 17530681.
30. ^ Abrams B (February 2005). "Gout is an indicator of sleep apnea”. Sleep 28 (2): 275. PMID 16171252.
31. ^ a b Zhang W, Doherty M, Bardin T, et al. (October 2006). "EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)". Ann. Rheum. Dis. 65 (10): 1312–24. doi:10.1136/ard.2006.055269.PMC 1798308. PMID 16707532.
32. ^ Schlesinger N et al. (2002). "Local ice therapy during bouts of acute gouty arthritis". J. Rheumatol. 29 (2): 331–4.doi:10.1093/rheumatology/29.5.331. PMID 11838852.
33. ^ a b Winzenberg T, Buchbinder R (July 2009). "Cochrane Musculoskeletal Group review: acute gout. Steroids or NSAIDs? Let this overview from the Cochrane Group help you decide what's best for your patient". J Fam Pract 58 (7): E1–4. PMID 19607767.
34. ^ Clinical Knowledge Summaries. "Gout - Management -- What treatment is recommended in acute gout?" National Library for Health. Retrieved 2008-10-26.
35. ^ Gout~Medication at eMedicine
36. ^ a b "Information for Healthcare Professionals: New Safety Information for Colchicine (marketed as Colcrys)". U.S. Food and Drug Administration.
37. ^ Man CY, Cheung IT, Cameron PA, Rainer TH (2007). "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial". Annals of emergency medicine 49 (5): 670–7. doi:10.1016/j.annemergmed.2006.11.014.PMID 17276548.
38. ^ a b c "FDA approves new drug for gout". FDA.
39. ^ Anderson A, Singh JA (2010). "Pegloticase for chronic gout”. Cochrane Database Syst Rev 3 (3): CD008335.doi:10.1002/14651858.CD008335.pub2. PMID 20238366.
40. ^ a b c Page 251 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008).Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
41. ^ Febuxostat for the management of hyperuricaemia in people with gout (TA164) Chapter 4. Consideration of the evidence
42. ^ a b Kim SY, De Vera MA, Choi HK (2008). "Gout and mortality". Clin. Exp. Rheumatol. 26 (5 Suppl 51): S115–9. PMID 19026153.
43. ^ Rheumatology Therapeutics Medical Center. "What Are the Risk Factors for Gout?" Retrieved 2007-01-26.
44. ^ Roberts-Thomson RA, Roberts-Thomson PJ (May 1999)."Rheumatic disease and the Australian aborigine". Ann. Rheum. Dis. 58 (5): 266–70. doi:10.1136/ard.58.5.266. PMC 1752880.PMID 10225809.
45. ^ Fam AG (May 2000). "What is new about crystals other than monosodium urate?” Curr Opin Rheumatol 12 (3): 228–34.doi:10.1097/00002281-200005000-00013. PMID 10803754.
46. ^ a b c d Pillinger, MH; Rosenthal P, Abeles AM (2007). "Hyperuricemia and gout: new insights into pathogenesis and treatment". Bulletin of the NYU Hospital for Joint Diseases 65 (3): 215–221.PMID 17922673.
47. ^ Kubitz possibly has gout."The Disease of Kings - Forbes.com".Forbes.
48. ^ "Rich Man's Disease - definition of Rich Man's Disease in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia”.
49. ^ "The Internet Classics Archive Aphorisms by Hippocrates". Retrieved July 27, 2010.
50. ^ "LacusCurtius • Celsus — On Medicine — Book IV".
51. ^ "BBC - h2g2 - Gout - The Affliction of Kings". BBC. Retrieved July 27, 2010.
52. ^ Storey GD (October 2001). "Alfred Baring Garrod (1819-1907)".Rheumatology (Oxford, England) 40 (10): 1189–90.doi:10.1093/rheumatology/40.10.1189. PMID 11600751.
53. ^ a b Agudelo CA, Wise CM (May 2001). "Gout: diagnosis, pathogenesis, and clinical manifestations". Curr Opin Rheumatol 13(3): 234–9. doi:10.1097/00002281-200105000-00015.PMID 11333355.
54. ^ Rothschild, BM; Tanke D, Carpenter K (1997). "Tyrannosaurs suffered from gout". Nature 387 (6631): 357.doi:10.1038/387357a0. PMID 9163417.
55. ^ "New therapeutic options for gout here and on the horizon - The Journal of Musculoskeletal Medicine".
? Porter, Roy (1998). Gout: the patrician malady. New Haven, Conn: Yale University Press. ISBN 0-300-08274-6.
? My Literary Malady - New York Times Book Review essay by novelist Geoff Nicholson