Tuesday, March 23, 2010

Stretching, Myofibroblasts and Dupuytren's

How, and why, does Dupuytren's disease actually contract? What is the physical mechanism? What provokes it? There is a genetic risk, but genes don't provide the entire script, otherwise Dupuytren's contractures should be symmetric, the same problem developing at the same time in the same way in both hands, but that's not what happens: usually, contractures in one hand are different in time and space than the other hand. Why? One explanation is that Dupuytren's is both biological and mechanical, and that physical forces somewhat influence the process. One way to study the big picture is to look at the little picture: what happens inside Dupuytren cells in response to physical forces? This is an active and exciting area of research. Myofibroblasts are the contracting cells producing Dupuytren's and other fibrotic contractures. Myofibroblasts respond to stretching by first relaxing and then pulling against the line of pull. This process is the subject of ongoing studies. In "Stretch-activated force-shedding, force recovery, and cytoskeletal remodeling in contractile fibroblasts" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Nekouzadeh.pdf), researchers used a laboratory model to demonstrate fibroblast reactions to stretch. Stretching cells initially tears the scaffolding inside cells, which is made of the protein actin. This releases tension, but also provokes the cells to pull back in two phases. The first phase starts within seconds ("Rapid Active Response"), the second after a few minutes ("Gradual Active Response"). These responses show the cell repairing the torn proteins. Other responses follow, modifying the collagen matrix outside the cells. The result? The more you pull, the more Dupuytren's pulls back. This is the type of data we need to move past what would seem to make sense, but is probably exactly wrong (pulling and stretching your fingers back to keep them from contracting) to an effective treatment, a cure.

Wednesday, March 17, 2010

Personal experiences with Xiaflex and Needle Aponeurotomy

Xiaflex is now available, and is generating reports by both traditional writers and self published social media authors. There are now two minimally invasive treatments for contractures due to Dupuytren's disease - Xiaflex injection and needle aponeurotomy - with relative advantages and disadvantages of each. The following video was made by a Dupuytren's patient, documenting experience with needle aponeurotomy: http://www.youtube.com/watch?v=lGD9RjmFBzo. Another person's documentary experience with Xiaflex, also with videos, is posted here: http://bit.ly/9RhqQA. Their experiences were different, but both are satisfied with their results. Every hand is different and no one treatment works for everyone, but it's great that there are new options to choose from to buy time while researchers work for a cure. The Dupuytren Foundation is actively recruiting volunteers and fund raising options to develop better treatments - and eventually a cure. Support the effort. Make a difference. http://www.DupuytrenFoundation.org

Thursday, March 11, 2010

Red wine and yellow curry to prevent Dupuytren's?

Could a yellow curry dinner and a glass of red wine be good for Dupuytren's? Possibly. Dupuytren's is a fibrotic condition, something it shares with other disorders. There is a great deal of ongoing research into the biology of fibrosis and its possible treatment. Two studies suggest that diet may have an helpful influence on excessive fibrosis, at least in special circumstances. In "Protective Effects Of Curcumin Against Amiodarone-Induced Pulmonary Fibrosis In Rats" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2003_Punithavathi.pdf), researchers found a protective effect against lung fibrosis of curcumin, found in turmeric, the spice which gives the yellow color to curry and yellow rice. Another group reported in "Ochratoxin A–Induced Renal Cortex Fibrosis and Epithelial-to-Mesenchymal Transition: Molecular Mechanisms of Ochratoxin A-Injury and Potential Effects of Red Wine" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2005_Gagliano.pdf) a protective effect of red wine against kidney fibrosis. These studies were performed on rats, testing against drugs known to cause fibrosis, which is a bit of a stretch to to Dupuytren's, but it's a start, if you are a rat, and possibly if you are human. Simple options are often the best. Keep looking for a cure!

Wednesday, March 10, 2010

A personal look at Dupuytren's

A family physician remembers his late father's Dupuytren's and muses on options for treatment: http://www.greatfallstribune.com/article/20100309/LIFESTYLE/3090307/Hands+become+claws+in+victims+of+Dupuytren+s. The observation "...in his final years he was wearied by the thought of 'another procedure' or treatment and decided to live with the condition" is a telling testimony for the need for better treatment options and the need to support efforts to find a cure for this common condition.

Sunday, March 7, 2010

The earliest case of Dupuytren's? You'll never guess where.

A case of Dupuytren's contracture has been discovered dating back nearly three thousand years. The Monthemhat Project, a multinational Egyptology group, recently published an analysis of 18 mummies from the Third Intermediate Period from the Luxor Cachette, and report the diagnosis of Dupuytren's contracture involving the left hand of one of the mummies. The full report, "Estudio Antropológico, Paleopatológico Y Radiológico De Las Momias Localizadas En El Almacen Número 4 De La Casa Americana (El Asasif, Luxor, Egypt): Proyecto Monthemhat 2009" is available here: http://www.dupuytrenfoundation.org/DupPDFs/2009_garciaguixe.pdf. The Third Intermediate Period refers to the time in Ancient Egypt from the death of Pharaoh Ramesses XI in 1070 BC to the foundation of the Twenty-Sixth Dynasty by Psamtik I in 664 BC. If this is true, this identifies a case of Dupuytren's nearly two thousand years before the previously earliest reports of Dupuytren's in Orkney and Iceland in the 12th and 13th centuries. The question is: were the Egyptians the secret ancestors of the Vikings?

Monday, March 1, 2010

Dupuytren's or palmar fasciitis?

Dupuytren's isn't the only problem which can affect the fascia of the palm. Inflammation of the palmar fascia (palmar fasciitis) may be due to less common problems, and differs from typical Dupuytren's in that it is usually painful. The difference between Dupuytren's and palmar fasciitis is similar to the difference between Ledderhose disease and plantar fasciitis - they are completely different problems which happen to affect the same stucture. Palmar fasciitis may be part of a syndrome associated with arthritis, as reported in "Idiopathic Palmar Fasciitis with Polyarthritis Syndrome" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2006_Sung.pdf), a problem following trauma as discussed in this hand surgery book exerpt (text: http://bit.ly/9Srduf) or part of a paraneoplastic syndrome associated with malignancy as reported in "Palmar fasciitis and polyarthritis as a paraneoplastic syndrome associated with tubal carcinoma: a case report" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2004_Denschlag.pdf). Fortunately or not, Dupuytren's is much more common than any of these conditions, but it is important to keep these in the list of possible diagnoses when evaluating a case of Dupuytren's which doesn't fit the typical picture.