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GoutPal Work In Progress
Gout research notes and planned projects.

The gout research notes that make up this site are not “polished” for publication, but may give you some insight into what is happening soon on GoutPal.com.

Moving GoutPal

I’m sure you’ve heard heard of moving gout, where gout moves from joint to joint.

One week it’s swollen toes, next it’s gouty knees.

All this, and much more about gout is explained at GoutPal.com, and discussed at Gout Pal Interactive.

Just like gout, it’s time for GoutPal to move.

I’ve taken some time out today from answering your gouty questions. I want to explain more about the GoutPal.com move to a new platform that I mentioned in my recent gout newsletter.

I’ve added a page here to explain the timetable for moving GoutPal.com. It also occurred to me that an explanation for why GoutPal has 3 websites is long overdue.

Allopurinol Dosage

Getting the right daily dose of allopurinol (or other uric acid lowering treatment), is vital to managing gout. Many gout patients wonder if the timing of their allopurinol dose makes any difference.

Most gout research on the topic of allopurinol dosage timing, suggests that timing is not important – just take the daily amount you need to manage uric acid levels properly.

Here are details of the relevant gout research, soon to be summarized on GoutPal.com.

JAMA. 1975 Mar 17;231(11):1143-7.
Allopurinol and gouty hyperuricemia. Efficacy of a single daily dose.
Rodnan GP, Robin JA, Tolchin SF, Elion GB.

The effect of daily administration of a single 300-mg tablet of allopurinol on serum urate levels was compared with the effect of divided doses of the drug (100 mg three times a day) in an open-labeled crossover trial of 20 patients with hyperuricemia and gout. Under both regimens of treatment there was a prompt fall in serum urate levels, and analysis of variance indicated no significant difference between the two modes of administration of allopurinol. Nor was there any significant difference in the minimum serum levels of oxypurinol. On the basis of this short-term study, the use of a single 300-mg tablet of allopurinol per day appears to be an effective means of lowering the elevated serum urate levels of individuals with gouty hyperuricemia and compares favorably with the results obtained by allopurinol in divided doses.

PMID: 1172813 [PubMed - indexed for MEDLINE]

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Ann Rheum Dis. 1975 Apr;34(2):201-2.
Proceedings: Single daily dose of allopurinol.
Brewis ID, Loebl WY, Scott JT.

PMID: 1137459 [PubMed - indexed for MEDLINE]

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Ann Rheum Dis. 1975 Jun;34(3):256-9.
Single daily dose of allopurinol.
Brewis I, Ellis RM, Scott JT.

Allopurinol was administered to seven patients with gout to compare the effects of three different methods of administration. Allopurinol 100 mg given three times daily. Allopurinol given once daily as three 100 mg tablets. Allopurinol given once daily as a single 300 mg tablet. Allopurinol as a single dose in the morning gave as sustained control of plasma levels as did divided administration.

PMID: 1098582 [PubMed - indexed for MEDLINE]

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Can Fam Physician. 1977 January; 23: 87, 89, 91.

PMCID: PMC2379056
Efficacy of Allopurinol In Single Daily Dose
D. Fraser, A. H. Little, and Wm. R. Bartle
Abstract
Allopurinol 300 mg once daily was compared with allopurinol, 100 mg tid in 17 patients with gouty arthritis and/or gouty nephrolithiasis. Weekly serum uric acid levels showed small but statistically significant differences between dosage regimens in four patients. Two acute attacks of gouty arthritis occurred in two different patients during once daily dosing of the allopurinol. There were no side effects attributable to the once daily dosage regimen.

Can Fam Physician – Canadian Family Physician – Official publication of the College of Family Physicians Of Canada

nephrolithiasis – kidney stones

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ACTH

ACTH is included in my list of gout treatment for pain guide. More gout research on ACTH is needed – and here is some:

Bulletin of the NYU Hospital for Joint Diseases 2008;66(3):231-9
Update on the Management of Hyperuricemia and Gout
Michael H. Pillinger, M.D., and Robert T. Keenan, M.D.

ACTH and Melanocortin Receptors: Old Becomes New Again
ACTH (adrenocorticotropic hormone) was the first steroid pathway agent used in rheumatic disease. Although its use in gout has largely been supplanted by prednisone, and though its availability in depot form is currently limited, ACTH is an effective treatment for acute gout [Taylor CT, Brooks NC, Kelley KW. Corticotropin for acute management of gout. Ann Pharmacother. 2001;35(3):365-8], and older rheumatologists speak anecdotally of its superior efficacy.

First described by Hench and Kendall, the antiinflammatory mechanism of ACTH action has long been presumed to be due to its ability to stimulate the adrenal production of corticosterone [Hench PS, Kendall EC, Slocumb CH, Polley HF. The anti-rheumatic effects of cortisone and pituitary ACTH. Trans Stud Coll Physicians Phila. 1950;18(3):95-102.]. However, ACTH is also a precursor molecule for melanocortin and is known to have activity at melanocortin receptors (MCR) [Getting SJ. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther. 2006;111(1):1-15.]. Based on these observations, Getting and coworkers have examined the possibility that ACTH may act to inhibit inflammation via engagement of one or more MCR.

Using a rat model of acute gout, they confirmed the ability of ACTH, injected subcutaneously, to stimulate increases in plasma corticosterone levels, as well as to reduce signs of inflammation such as neutrophil influx. However, they also demonstrated the ability of lower concentrations of ACTH, injected directly into the joint to inhibit joint inflammation without increasing corticosterone levels [Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone eficacy in gouty arthritis.
Arthritis Rheum. 2002;46(10):2765-75.]. Thus, ACTH must have antiinflammatory properties independent of its effect on glucocorticoid release. Further studies by Getting and associates have demonstrated the ability of MCR antagonists to reverse the antiinflammatory effect of ACTH and the ability of selective agonists of MCR—particularly MCR3—to suppress gouty inflammation [Getting SJ, Lam CW, Chen AS, et al. Melanocortin 3 receptors control crystal-induced inlammation. Faseb J. 2006;20(13):2234-41.
Getting SJ, Allcock GH, Flower R, Perretti M. Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties. J Leukoc Biol. 2001;69(1):98-104.]. These data suggest that MCR3 agonists may be useful antiinflammatory drugs. Whether such agents will prove useful in human gout
has yet to be tested.

Iron homoeostasis in rheumatic disease

More research on the gout and iron problem.

GoutPal latest is at Alternative Treatment For Gout – Blood Letting.

Gout research from Rheumatology (Oxford). 2009 Jul 23.
[Epub ahead of print]
Iron homoeostasis in rheumatic disease.

Baker JF, Ghio AJ.

Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA and Human Studies Division, US EPA, Chapel Hill, NC, USA.

Iron is critical in nearly all cell functions and the ability of a cell, tissue and organism to procure this metal is obligatory for survival. Iron is necessary for normal immune function, and relative iron deficiency is associated with mild immunosuppression. Concentrations of this metal in excess of those required for function can present both an oxidative stress and elevate risks for infection. As a result, the human has evolved to have a complex mechanism of regulating iron and limiting its availability. This homoeostasis can be disrupted. Autoimmune diseases and gout often present with abnormal iron homoeostasis, thus supporting a participation of the metal in these injuries. We review the role of iron in normal immune function and discuss both clinical evidence of altered iron homoeostasis in autoimmune diseases and gout as well as possible implications of both depletion and supplementation of this metal in this patient population. We conclude that altered iron homoeostasis may represent a purposeful response to inflammation that could have theoretical anti-inflammatory benefits. We encourage physicians to avoid routine iron supplementation in those without depleted iron stores.

PMID: 19628641 [PubMed - as supplied by publisher]

Dictionary / research notes:
iron homeostasis – The ability or tendency of people to balance iron available to cells by storing and releasing it from reserves.

Colchicine Dosing

Hot on the heals of the new colchicine brand (Colcrys) article, a summarizing piece on zip2play’s colchicine dosing recommendations is well past due.

Allopurinol A Lifesaver

Gout Research:

Also see Allopurinol Tablets Give Kidney Disease Relief

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Allopurinol and mortality in hyperuricaemic patients.

Luk AJ, Levin GP, Moore EE, Zhou XH, Kestenbaum BR, Choi HK.

Department of Medicine, Division of Rheumatology, University of British Columbia, Arthritis Research Centre of Canada, 895 West 10th Avenue, Vancouver, BC V5Z 1L7, Canada. hchoi@arthritisresearch.ca.

Objectives

While studies have suggested that gout and hyperuricaemia are associated with the risk of premature death, none has investigated the role of urate-lowering therapy on this critical outcome. We examined the impact of allopurinol, the most commonly used urate-lowering drug, on the risk of mortality in hyperuricaemic patients.

Methods

From a population of hyperuricaemic veterans of [serum urate level >416 mumol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n = 2483) and non-users (n = 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models.

Results

Of the 9924 veterans (males, 98% and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95% CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95% CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was -111 mumol/l (-1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 mumol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95% CI -0.55, -0.81).

Conclusion

Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.

PMID: 19447769 [PubMed - in process]
Rheumatology (Oxford). 2009 Jul;48(7):804-6. Epub 2009 May 15.

Adjust / explain
hyperuricaemia = hyperuricemia

Gout Joint Aspiration

New review data to update:

• Gout Forum : Joint Aspiration
• Painful, swollen or tingling joints? See these signs and symptoms of gout

Gout Joint Aspiration / Arthrocentesis review from:
Best Pract Res Clin Rheumatol. 2009 Apr;23(2):161-92.
Joint aspiration and injection and synovial fluid analysis.

Courtney P, Doherty M.

Nottingham City Hospital, Nottingham, UK.

Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable procedures for the diagnosis and treatment of joint disease. This chapter addresses: (1) the indications, the technical principles and the expected benefits and risks of aspiration and injection of intra-articular corticosteroid; and (2) practical aspects relating to SF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is a well-established procedure that produces rapid pain relief and resolution of inflammation in most injected joints. The knee is the most common site to require aspiration, although any non-axial joint is accessible for obtaining SF. The technique requires a knowledge of basic anatomy and should not be unduly painful for the patient. Provided sterile equipment and a sensible, aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful in the differential diagnosis of arthritis and is the definitive method for diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF can provide useful diagnostic information in terms of the degree of joint inflammation and presence of haemarthrosis. Microbiological studies of SF are the key to the confirmation of infectious conditions. Increasing joint inflammation is associated with increased SF volume, reduced viscosity, increasing turbidity and cell count, and increasing ratio of polymorphonuclear: mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However, detection of SF monosodium urate and calcium pyrophosphate dihydrate crystals, even from un-inflamed joints during intercritical periods, allow a precise diagnosis of gout and of calcium pyrophosphate crystal-related arthritis.

PMID: 19393565 [PubMed - in process]

Gout Resource

Best Pract Res Clin Rheumatol – Best practice & research. Clinical rheumatology – http://www.elsevier.com/wps/find/journaldescription.cws_home/623005/description#description

Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions

Best Practice and Research Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science.

Iron Test

In the continuing quest to understand the effect of iron on gout, I’m looking at test levels

This is part of my research project into gout and iron prompted by Near-iron deficiency-induced remission of gouty arthritis.

Blood Iron Testing

Adult Health Advisor 2005.4:
Serum iron

For men and women the normal range is 20 to 150 ng/mL.

Total iron binding capacity (TIBC)

For men and women the normal range is 250 to 450 ng/mL.

Ferritin

* Males: 20 to 300 nanograms per milliliter (ng/mL)
* Females: 20 to 120 ng/mL

Results of these iron studies tests may mean the following:

* A low serum iron level and low serum ferritin level may be caused by iron deficiency anemia.
* A high TIBC and low serum iron level may be caused by iron deficiency anemia, pregnancy, and chronic blood loss.
* A high serum iron level may be caused by too much iron in your diet, vitamin B6 therapy, or some anemias caused by an inability to use iron.
* A high ferritin level and a normal serum iron level might indicate liver disease from infection or alcoholism, chronic inflammatory disease (such as arthritis or asthma), hypothyroidism, and type 2 diabetes.
* A high ferritin level combined with a high serum iron level may be a sign of hemosiderosis (an accumulation of iron in some of your tissues).
* A low TIBC and high serum iron may be a sign of sideroblastic anemia (a condition that prevents your red blood cells from using iron).
* A high serum ferritin level, high serum iron, and low TIBC may be caused by hemochromatosis.

MedlinePlus Medical Encyclopedia:
Normal Results

• Iron: 60-170 mcg/dL
• TIBC: 240-450 mcg/dL

  Total iron binding capacity (TIBC) is a blood test that shows if there is too much or too little iron in the blood. Iron is carried in the blood attached to the protein transferrin. This test helps measure the ability of a protein called transferrin to carry iron in the blood.

• Transferrin saturation: 20-50%

Gout Treatment

Free Gout Pain Treatment Guide now available on Scribd.

View this document on Scribd

For full description and other guides see Gout Treatment For Pain: 7 Prescriptions.

What other free guides would you like to see? What are your top 3 gout questions?

Comment below, or better still, discuss in the gout guide forum.