Professor of Medicine
HUP Clinic: 8 Penn Tower
34th & Civic Center Boulevard
Philadelphia, PA 19104
VA Medical Center, Arthritis Clinic
University & Woodland Avenues
Philadelphia, PA 19104
Office: 215-823-5979
Fax: 215-823-6032
Email: schumacr@mail.med.upenn.edu
Visit My Website on Synovial Biopsy, Synovium, Synovial Fluid and Arthrocentesis: http://www.med.upenn.edu/synovium/
Research Programs
Arthritis of Recent Onset (Reactive arthritis, rheumatoid arthritis)
Program Summary
We have proposed that important initiating mechanisms for arthritis that may be more amenable to therapy need further study. In this project we have evaluated all patients with inflammatory arthritis of unknown cause searching for infectious triggers, characterizing immunogenetic background and tallying ongoing inflammatory mechanisms in joints with biopsies and joint fluid testing including PCR, in situ hybridization, immunohistology and cytokine biochemistry. We have reported chlamydial antigen and chlamydial ribosomal RNA in synovial macrophages suggesting possibly latent infection amenable to antibiotic therapy or manipulation of cytokines that control bacterial activity in reactive arthritis. Pathologic changes can even be present before symptoms or overt swelling making data of exact and key initial changes difficult to assess. One current focus is on trying to identify if patients with only arthralgia actually have objective changes in the joint detectable with ultrasoiund, MRI, arthrocentesis or synovial biopsy. Another active project involves study of synovium recent onset psoriatic arthritis.
Publications
1. Schumacher HR, Magge S, Cherian PV, Sleckman J, Rothfuss S, Clayburne G and Sieck M: Light and electron microscopic studies on the synovial membrane in Reiter's syndrome. Arthritis Rheum 31:937-946, 1988.
2. Cheema MA, Schumacher HR, Hudson AC: RNA-Directed molecular hybridization screening: Evidence for inapparent chlamydial infection. Am J Med Sci 302:261-268, 1991.
3. Rahman MU, Shenberger KN, Schumacher HR: Initially unrecognized calcium pyrophosphate dihydrate deposition disease as a cause of fever. Am J Med 89:115-116, 1990.
4. Rahman MU, Ahmed S, Schumacher HR, Zeiger AR: High levels of antipeptidoglycan antibodies in psoriatic and other seronegative arthritides. J Rheumatol 17:621-625, 1990.
5. Rahman MU, Cantwell R, Johnson CC, Hodinka RL, Schumacher HR, Hudson AP: Inapparent genital infection with Chlamydia trachomatis and its potential role in the genesis of Reiter's syndrome. DNA Cell Biol 11:215-219, 1992.
6. Rahman MU, Cheema MA, Schumacher HR, Hudson AP: Molecular evidence for the presence of Chlamydia in the synovium of patients with Reiter's syndrome. Arthritis Rheum 35:521-529, 1992.
7. Baker DG, Schumacher HR: Acute monoarthritis. New Engl J Med 329:1013-1020, 1993.
8. Schumacher HR, Bautista BB, Krauser RE, Mathur AK, Gall EP:Histological appearance of the synovium in early RA, Salameh WA and Hudson AP: Case Report: In SituHybridization for Detection of inapparent infection with chlamydia trachomatis in synovial tissue of a patient with Reiter's syndrome. Am J Med Sci 310:206-213, 1995.
9. Beutler AM, Schumacher HR, Whittum—Hudson JA, Salameh WA and Hudson AP: Case Report: In Situ Hybridization for Detection of inapparent infection with chlamydia trachomatis in synovial tissue of a patient with Reiter’s syndrome. Am J Med Sci 310:206—213, 1995.
10. Nanagara R, Li F, Beutler A, Hudson A and Schumacher HR: Alteration of chlamydia trachomatis biologic behavior in synovial membranes. Arth & Rheum 38:1410—1417, 1995.
11. Ramanujam T, Luchi M, Schumacher HR, Zwillich S, Chang CP etc: Detection of T cell receptors in early rheumatoid arthritis synovial tissue. Pathobiology 63:100—108, 1995.
12. Li F, Bulbul R, Schumacher HR, Kieber—Emmons T, Callegari P, VonFeldt, J etal: Molecular detection of bacterial DNA in Venereal—associated arthritis. Arthritis & Rheumatism 39:950—958, 1996.
13. Branigan PJ, Gerard HC, Hudson AP, Schumacher HR: Comparison of synovial tissue and synovial fluid as the source of nucleic acids for detection of Chlamydia Trachomatis by polymerase chain reaction. Arth Rheum 39:1740—6, 1996.
14. Nanagara R, Duray PH, Schumacher HR: Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic lyme disease: Possible factors contributing to persistence of organisms. Human Pathology 27:1025—1034, 1996.
15. Branigan PJ, Gerard HC, Hudson AP, Schumacher HR: Comparison of synovial tissue and synoival fluid as the source of nucleic acids for detection of Chlamydia Trachomatis by polymerase chain reaction. Arth Rheum 39:1740-6, 1996.
16. Nanagara R, Duray PH, Schumacher HR: Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane inchronic lyme disease: Possible factors contributing to persistence of organism. Human Pathology 27:1025-1034, 1996
17. Pras E, Schumacher HR, Kastner DL, Wilder RL: lack of evidence of mycobacteria n synovial tissue from patients with rheumatoid arthritis. Arth Rheum 39:2080-1, 1996
18. Koehler L, Netteinbreker E, Hudson AP, Ott N, Gerard HC, Branian PJ, Schumacher HR, Drommer W, & Zeidler H: Ultrastructural and molecular analyses of the persistence of Chlamydia trachomatis (serovar K) in human monocytes.Microbial Pathogenesis 22:133-142, 1997.
19. Beutler AM, Hudson AP, Whittum-Hudson JA, Salameh WA, Gerard HC, Branigan PJ, Schumacher HR: Chlamydia trachomatis can persist in joint itssue after antiboitic treatment in chronic Reiter’s syndrome/Reactive Arthritis. J. of Clin Rheum: (3): 125-130, 1997.
20. Kotake S, Schmacher HR, Yarboro CH, Arayssi TK, Pando JA, Kanik KS, Gourley MF, Klippel JH and Wilder RL: In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive, and undifferentiated arthritis. Proc Assoc of Am Phys 109:286-302, 1997.
21. File TM, Bartlett JG, Cassell GH, Gaydo CA, Grayston JT, Hammerschlag MR, Jones RB, Kahn JB, Marrie TJ,Ramirez JA, aikku P, Schachter J, Schumacher HR, Stamm WE, Stratton CW and Yu VL: The importance of chlamydia diapneumoniae as a pathogen: The 1996 concensus conference on chlamydia pneumoniae infections. Inf Dis in Clin Prac 6(2 Suppl): S28-S31, 1997.
22. Kanik KS, Hagiwara E, Yarboro CH, Schumacher HR, Wilder RL and Klinman DM: Distinct patterns of cytokine secretion characterize new onset synovitis versus chronic rheumatoid arthritis. J Rheumatol 25:16-22, 1998.
23. Gerard HC, Branigan PJ, Schumacher HR and Hudson AP: Synovial Chlamydia trachomati in patients with Reactive arthritis/Reiter’s syndrome are viable but show aberrant gene expression. J Rheumatol 25: 734-42, 1998.
24. Arayssi TK and Schumacher HR: Evaluation of a modified needle for small joint biopsies. J. Rheumatolol 25:876-8, 1998.
25. Schumacher HR: Reactive arthritis. Rheumatic Dis Clin of North America 24:261-273, 1998
26. Gerard HC, Wang Z, Wang GF, El-Gabalawy H, Goldbach- Mansky R, Li Y, Majeed W, Zhang H, Ngai N, Hudson AP, and Schumacher HR: Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis. Arthritis Rheum 44: 1689-1697, 2001.
27. Berthelot JM, Klarlund M, McGonagle D, Bernolet- Moens HJ, Calin A, Harrison B, Schumacher HR, et al: Lessons from an internationl survey of paper cases of 10 real patients from an arthritis clinic. J Rheumatol 28: 975-81, 2001.
28. Van Riel PLCM, Schumacher HR: How does one assess early rheumatoid arthritis in daily clinical practice? Best Practice Res Clin Rheumatol 15: 67-76, 2001.
29. Goldbach-Mansky R, Lee JM, Hoxworth JM, Smith D 2nd, Duray P, Schumacher HR, Yaboro CH, Klippel J, Kleiner D, El- Gabalawy H: Active synovial matrix metalloproteinase- 2 is associated with radiographic erosions in patients with early synovitis. Arthritis Res 2: 145-153, 2000.
30. Goldbach-Mansky R, Lee J, McCoy A, Hoxworth JM, Yarboro C, Smolen JS, Steiner G, Rosen A, Zhang C, Menard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, Klippel JH, Schumacher HR, El- Gabalway H: Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset, Arthritis Res 2: 236-243, 2000.
31. Gerber L, El- Gabalawy H, Arayssi T, Furst G, Yarboro C, Schumacher HR: Polyarticular arthritis, independent of rheumatoid factor, is associated with poor functional outcome in recent onset inflammatory synovitis. J Back Musculo Rehab 14: 105-109, 2000.
32. Pando JA, Duray P, Yarboro C, Gourley MF, Klippel JH, Schumacher HR: Synovitis occurs in some clinically normal and asymptomatic joints in patients with early arthritis. J Rheumatol 27:1848-1854, 2000.
33. Schumacher HR: Chlamydia- associated reactive arthritis. Israel Medical Assoc J 2: 532-535, 2000
34. Kanik KS, Chrusos GP, Schumacher HR, Crane ML, Yarboro CH, Wilder RL. Adrenocorticotrpin, glucocorticoid, and androgen secretion in patients with new onset synovitis/ rheumatoid arthritis: Relations with indices of inflammation. J Clin Endocrinol Metab 85: 1461-1466,2000.
35. Schumacher HR, Gerard HC, Arayssi TK, Pando JA, Branigan PJ, Saaibi DL and Hudson AP: Lower prevalence of chlamydia pneumoniae DNA compared with chlamydia trachomatis DNA in synovial tissue of arthritis patients. Arthritis Rheum 42:1889-93, 1999.
36. El- Gabalway HS, Goldbach- Mansky R, Smith D, Arayssi T, Bale S, Gulko P, Yarboro C, Wilder RL, Klippel JH and Schumacher HR: Association of HLA Alleles and clinical features in patients with synovitis of recent onset. Arth Rheum 42:1696-1705.
37. Kotake S, Schumacher HR, Arayssi TK, Gerard HC, Branigan PJ, Hudson AP, Yarboro CH, Klippel JH, Wilder RL: Gamma interferon and interleukin-10 expression in synovial tissues arthritits and undifferentiated oligoarthritis and from healthy volunteers. Infection and Immunity 67:2682- 86, 1999.
38. Fang Q, Sun YY, El- Gabalawy H, Cai W, Ko L, Chin H, Arayssi T, Schumacher HR, Williams WV: Synovial T Cell receptor heterogeneity in early arthritis. Pathbiology 67:59-74, 1999.
39. Schumacher HR: The spondylarthopathies: classification and diagonsis. Do we need new terminologies? Bailliere’s Clinical Rheumatology 12:551-565, 1998.
40. Brennan MT, Pillemer SR, Goldbach- Mansky R, El- Gabalawy H, Schmacher HR, Fox PC: Focal sialadenitis in patients with early synovitis. Clin Exper Rheumatol 19: 444-446,2001.
41. Goldbach-Mansky R, Lee JM, Hoxworth JM, Smith D 2nd, Duray P, Schumacher HR, Yarboro CH, Klippel J, Kleiner D, El-Gabalawy H: Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis. Arthritis Res 2: 145-153, 2000.
42. Goldbach-Mansky R, Lee J, McCoy A, Hoxworth JM, Yarboro C, Smolen JS, Steiner G, Rosen A, Zhang C, Menard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, Klippel JH, Schumacher HR, El-Gabalawy H. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset, Arthritis Res 2: 236-243, 2000.
43. van Riel PLCM, Schumacher HR: How does one assess early rheumatoid arthritis in daily clinical practice? Best Pract Res Clin Rheumatol 15: 67-76, 2001.
44. Berthelot JM, Klarlund M, McGonagle D, Bernolet-Moens HJ, Calin A, Harrison B, Schumacher HR, et al: Lessons from an international survey of paper cases of 10 real patients from an early arthritis clinic. J Rheumatol 28: 975-81, 2001.
45. Gérard HC, Wang Z, Wang GF, El-Gabalawy H, Goldbach-Mansky R, Li Y, Majeed W, Zhang H, Ngai N, Hudson AP, Schumacher HR: Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis. Arthritis Rheum 44: 1689-1697, 2001.
46. Gerard HC, Krausse-Opatz B, Wang Z, Rudy D, Rao JP, Zeidler H, Schumacher HR, Whittum-Hudson JA, Kohler L, Hudson AP: Expression of Chlamydia trachomatis genes encoding products required for DNA synthesis and cell division during active versus persistent infection. Molecular Micribiol 41:731-741, 2001.
47. Bertholet JM, Bernelot-Moens HJ, Klarlund M, McGonagle D, Calin A, Schumacher HR, Combe B, De Bandt M, Drosis AA, Flipo RM, Harrison BJ, Kaarela K, Le Goff P, Meyer O, Punzi L, Zerbini CA, Saraux A, The CRI Group: Differences in understanding and application of 1987 ACR criteria for rheumatoid arthritis and 1991 ESSG criteria for spondyloarthropathy. A pilot survey. Clin Exp Rheumatol 20:145-150, 2002.
48. Gerard HC, Wang Z, Whittum-Hudson JA, El-Gabalawy H, Goldbach-Mansky R, Bardin T, Schumacher HR, Hudson AP: Cytokine and chemokine mRNA produced in synoval tissue chronically infected with Chlamydia trachomatis and C. pneumoniae. J Rheumatol 29: 1827-1835, 2002.
49. Meador R, Hsia E, Kitumnuaypong T, Schumacher HR: TNF involvement and anti-TNF therapy of reactive and unclassified arthritis. Clin Exp Rheumatol 20: s130-134, 2002.
50. Schumacher HR: Early Arthritis Clinics. Much Early Arthritis is Unclassified. J Rheumatol 29:2258-2260, 2002.
51. Schumacher HR, Pessler F, Chen L: Diagnosing early rheumatoid arthritis (RA). What are the problems and opportunities? Clinical and Experimental Rheumatology 21:S15-S19, 2003.
52. Schumacher HR, Habre W, Meador R, Hsia E: Predictive Factors in Early Arthritis: Long-Term Follow-up. Arthritis and Rheumatism 33:4, 264-272, 2004.
53. Singh JA, Pando JA, Tomaszewski J, Schumacher HR: Quantitative analysis of immunohistologic features of very early rheumatoid synovitis in disease modifying antirheumatic drug- and corticosteroid-naïve patients. J Rheum 31:1281-1285, 2004.
54. Flagg SD , Meador R, Hsia E, Kitumnuaypong T & Schumacher HR: Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: An open-label trial. Arthritis Rheum. 53:613-617, 2005.
55. Newkirk MM, Goldbach-Mansky R, Senior BW, Klippel J, Schumacher HR, El-Gabalawy HS: Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis. Rheumatology ( Oxford) 44:1433-41, 2005.
56. Gerard HC, Whittum-Hudson JA, Schumacher HR, Hudson AP: Synovial Chlamydia trachomatis up regulates expression of a panel of genes similar to that transcribed by Mycobacterium tuberculosis during persistent infection. Ann Rheum Dis. 65:321-327, 2006.
57. Kuipers JG, Sibilia J, Bas S, Gaston H, Granfors K, Vischer TL, Hajjaj-Hassouni N, Ladjouze-Rezig A, Sellami S, Wollenhaupt J, Zeidler H, Schumacher HR, Dougados M. Reactive and undifferentiated arthritis in North Africa: use of PCR for detection of Chlamydia trachomatis.Clin Rheumatol. Aug 8. 2008 [Epub ahead of print].
58. Pessler F, Chen LX, Dia L, Gomez-Vaquero C, Diaz-Torne C, Paessler ME, Scanzello C, Cakir N, Einhorn E. and Schumacher HR. A histomorphometric analysis of synovial biopsies from individuals with Guf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheum. 27:1127-34, 2008. Epub ahead of print April 15, 2008.
59. Gerard HC, Stanich JA, Whittum-Hudson JA, Schumacher HR, Carter JD, Hudson AP. Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue. Microb Pathog . 48:62-68;2010. Epub Nov18 20.
60. Gérard HC, Stanich JA, Oszust CE, Whittum-Hudson JA, Carter JD, Schumacher HR, Hudson AP. Functional CCR5 receptor protects patients with arthritis from high synovial burden of infecting Chlamydia trachomatis. Am J Med Sci. 340:448-51; 2010.
61. Ogdie A, Schumacher HR Jr, Dai L, Chen LX, Einhorn E, Pessler F Synovial biopsy findings in arthritis associated with hepatitis C virus infection. J Rheumatol. 37:1361-3; 2010.
Pathogenesis of Crystal Induced Inflammation
Program Summary
Studies from this laboratory over more than 30 years have examined the roles of cells, particles, and associated proteins in monosodium urate crystal induced acute inflammation. Reviews have identified the paucity or controlled trials in acute or chronic gout. Attention has been directed at the low grade destructive inflammatory and proliferative process associated with calcium phosphate (apatite) crystals and with other particles including silicone, metals, and cements used in total joint replacements. Apatites are a virtually uniform accompaniment of osteoarthritis and their role in this disease is being investigated. The rat airpouch model of urate crystal induced inflammation is used to study the sequence of changes produced by crystals, new therapies including anti IL8, COX 2 inhibitors and herbs. We are studying epidemiology of gout and the possible role of uric acid or gouty inflammation in the co-morbidities such as cardiovascular disease.
Publications
1. Fam AG, Schumacher HR, Clayburne G. Villanueva T, Baker DG, Jimenez SA: Effect of joint motion on experimental calcium pyrophosphate dihydrate crystal induced arthritis. J Rheumatol 17:644-655, 1990.
2. Ortiz-Bravo E, Sieck M, Schumacher HR: Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Arthritis Rheum 36:1274-1285, 1993.
3. Beutler A, Rothfuss S, Clayburne G, Sieck M, Schumacher HR:Calcium pyrophosphate dihydrate crystal deposition in synovium. Relationship to collagen fibers and chondrometaplasia. Arth Rheum 36: 704—715, 1993
4. Ortiz-Bravo E, Baker DG, Schumacher HR: Mechanisms involved in the initiation, perpetuation and self-limited nature of acute gouty arthritis. Revue Du Rhumatisme (English edition) 61:121 126, 1994.
5. Schumacher HR: Synovial inflammation, crystals, and osteoarthritis. J Rheum 22:101-103, 1995.
6. VanLinthoudt D, Salani I, Zender R, Locatelli P, Ott H and Schumacher HR: Citrate in synovial fluid and its relation to inflammation and crystal presence. J Rheum 23:502-5, 1996.
7. Ferrari AJL, Van Linthoudt D, Morrone L, Branigan P, Schumacher HR and Baker DG: Nonsteroidal anti-inflammatory drugs and prosstaglandins: Their interactions and effects on the particulate-induced inflammatory process implicated in joint implant-loosening and on monosodium urate crystal-induced inflammation. Am J of Therapeutics 3:189-194, 1996.
8. Beutler A, Keenan GF, Soloway S, Norden D, Luchi M, Schumacher HR: Soluble urate in sera and synovial fluids from patients with different joint disorders. Clin Exp Rheum 14:249-254, 1996.
9. Ferrari AJL, Rothfuss S, Schumacher HR: Dialysis arthropathy: Identification and evaluation of a subset of patients with unexplained inflammatory effusions. J. Rheumatol 24:1780-6, 1997.
10. Ward M, CureJ, Schabel S, Smith EA, Schumacher HR and Silver RM: Symptomatic spinal calcinosis in systemic sclerosis (Scleroderma). Arth Rheum 40:1892-1895, 1997.
11. VanLinthoudt D, Beutler A, Clayburne G, Sieck M, Fernandes L and Schumacher HR: Morphometric studies on synovium in advanced osteoarthritis: Is there an association between apatite-like material and collagen deposits? Clin and Exper Rheumatol 15:493-497, 1997.
12. Schlesinger N, Gowin KM, Baker DG, Beutler AM, Hoffman BI and Schumacher HR: Acute gouty arthritis is seasonal. J. Rheumatol 25:324-4, 1998.
13. Olmez N, Schumacher HR: Crystal deposition and osteoarthritis. Current Rheumatol Reports 1:107-11, 1999.
14. Meng ZH, Baker DG, Branigan P, Park J, Baker S, Rao J, Schumacher HR: Hydroxychloroquine inhibits matrix metalloprotease activity in experimental calcium pyrophospate dihydratre (CPPD) crystal induced inflammation in the rat subcutaneous air pouch . Inflammopharmacology 8: 113-21, 2000.
15. Li- Yu J, Schumacher HR, Gratwick G: Invasive tophaceous pseudogout in the temporomandibular joint: misdiagnosis as tumor. J Clinc Rheumatol 6:272-277, 2000.
16. Rashad SM, Abdelaty EM, Rooney J, Schumacher HRS: Acute inflammation at the site of calcinosis in limited cutaneous scleroderma [Letter]. J Rheumatol 29: 402-403,2002.
17. Li-Yu J, Clayburne GM, Sieck MS, Walker SE, Athreya BH, DeHoratius RJ, Schumacher HR: Calcium apatite crystals in synovial fluid rice bodies. Ann Rheum Dis 61:387-390, 2002.
18. Rull M, Clayburne G, Sieck M, Schumacher HR. Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch. Rheumatology 42:1093-1100, 2003.
19. Chen LX, Clayburne G, Schumacher HR: Update on identification of pathogenic crystals in joint fluid. Cur Rheum Rep 6:217-220, 2004.
20. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR, Saag KG: Gout epidemiology: results from the UK general practice research database, 1990-1999. Ann Rheum Dis 64:267-272, 2005.
21. Baker JF, Krishnan E, Chen L & Schumacher HR: Serum uric acid and cardiovascular disease: recent developments, and where do they leave us? Am J of Med. 118:816-826, 2005.
22. Krishnan E, Baker JF, Furst DE & Schumacher HR: Gout and the risk of acute myocardial infarction. Arthritis & Rheumatism 54:2688-2696, 2006.
23. Padang C, Muirden KD, Schumacher HR, Darmawan J, Nasution AR: Characteristics of Chronic Gout in Northern Sulawesi, Indonesia. J Rheumatol 9:1813-1817, 2006.
24. Krishnan E, Kwoh CK, Schumacher HR, Kuller L. Hyperuricemia and incidence of hypertension among men without metabolic syndrome.Hypertension 49:298-303, 2007. Epub Dec 26 2006.
25. Baker JF, Schumacher HR, and Krishnan E. Serum uric acid level and risk for peripheral arterial disease: analysis of data from the multiple risk factor intervention trial. Angiology 58:450-7, 2007.
26. Schumacher HR. The pathogenesis of gout. Cleveland J Med Suppl 5: S2-S4, 2008.
27. Pessler F, Mayer CT, Jung SM, Behrens EM, Dai L, Menetski JP, and Schumacher HR. Identification of novel monosodium urate crystal regulated mRNAs by transcript profiling of dissected murine air pouch membranes. Arthritis Res Ther 10:R64, 2008. Epub 2008 Jun 3.
28. Malik A, Schumacher HR, Dinnella JE , Clayburne GM. Clinical Diagnostic Criteria for Gout: Comparsion With the Gold Standard of Synovial Fluid Crystal Analysis. J Clin Rheumatol 15:22-24; 2009.
29. Chen CJ, Schumacher HR. Adenine phosphoribosyltransferase deficiency in a Chinese man with early-onset gout. J Rheumatol.36:1090-1; 2009.
30. Schlesinger N, Hassett A, Neustadter L, Schumacher HR, Jr. Does acute synovitis (pseudogout) occur in patients with chronic pyrophosphate arthropathy (pseudo-osteoarthritis)? Clin Exp Rheumatol 27:940-944; 2009.
Treatment of Crystal Associated Diseases
Program Summary
Clinical studies have examined therapy of both acute gout and hyperuricemia. Clinical trials examine underevaluated aspects of clinical treatment of gout and include studies on use of the new coxibs for gout as well as adjunct measures such as application of cold to gouty joints. Studies are also done on new urate lowering agents that will be alternatives in allopurinol allergic patients and on interleukin 1 antagonists for prophylaxis and treatment of acute gout. We are comparing the effects of febuxostat vs. allopurinol on cardiovascular outcomes. We are coordinating omeract and cochrane surveys on evidence based diagnosis and treatment of gout and doing database studies on gout in the VA system. With a grant from ACR and EULAR we are developing validated international criteria for response to treatment of gout. We are developing treatment guidelines with ACR.
Publications
1. Hasselbacher P, Schumacher HR, Simkin PA: Gout: Applying current knowledge. Patient Care (32)10:125-139, 1998.
2. Schlesinger N, Baker DG and Schumacher HR: How well have diagnostic tests and therapies for gout been evaluated? Curr Opin Rheumatol11:441-445, 1999.
3. Li-Yu J, Clayburne G, Sieck M, Beutler A, Rull M, Eisner E, Schumacher HR: Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol 28: 577-580, 2001.
4. Schlesinger N, Schumacher HR: Gout: Can mangement be improved? Current Opinion in Rheumatol 13:240-244, 2001.
5. Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M, Hoffman BI, Schumacher HR: Local ice therapy during bouts of acute gouty arthritis. J Rheumatol 29: 331-334, 2002.
6. Beutler AM, Rull M, Schlesinger N, Baker DG, Hoffman BT, Schumacher HR: Treatment with allopurinol decreases the number of acute gout attacks despite persistently elevated serum uric acid levels [Letter]. Clin Exper Rheumatol 19:595,2001.
7. Schumacher HR, Boice HA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J, Tate GA, Molina J: Randomixed double blind trial or etoricoxib and indometacin in treatment of acute gouty arthritis. Br Med J 324:1488-1492, 2002.
8. Schumacher HR: Management of Gout: Why is it still difficult? New Horizons: Changing Paradigms in Primary Care 8:11-15, 2002.
9. Schlesinger N, Schumacher HR: Update on Gout. Arthitis Rheum 47: 563-565, 2002.
10. Chen LX, Schumacher HR: Gout and gout mimickers: 20 clinical pearls. J Musculo Med 20:254-258, 2003.
11. Chen LX, Schumacher HR: Diagnosis and management of gout: case study and commentary. JCOM 10:336-342, 2003.
12. Kim KY, Schumacher HR, Hunsche E, Wertheimer AL, Kong SX: A literature review of the epidemiology and treatment of acute gout. Clin Ther 25:1593-1617, 2003.
13. Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Palo WA, Eustace D, Vernillet L, Joseph-Ridge N: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. Arth & Rheum 52:916-923, 2005.
14. Schumacher HR, Wortmann RL: Monosodium urate crystal deposition arthropathy Part I: Review of the stages and diagnosis of gout. Adv Stud Med. 5:133-138, 2005.
15. Wortmann RL, Schumacher HR: Monosodium urate crystal deposition arthropathy Part II: Treatment and long-term management of patients with gout. Adv Stud Med. 5:183-194, 2005.
16. Schumacher HR: Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout. Expert Opin. Investig. Drugs. 14:893-903, 2005.
17. Nalbant S, Chen LX, Sieck MS, Clayburne G & Schumacher HR: Prophylactic effect of highly selective COX-2 inhibition in acute monosodium urate crystal induced inflammation in the rat subcutaneous air pouch. J Rheum 32:1762-1764, 2005.
18. Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace E, Palo WA, Streit J & Joseph-Ridge N: Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 353:2450-61, 2005.
19. Schumacher HR, Becker MA, Palo WA, Streit J, MacDonald PA & Joseph-Ridge N: Tophaceous gout: quantitative evaluation by direct physical measurement. J Rheumatol 32:2368-72, 2005.
20. Schumacher HR, Edwards LN, Perez-Ruiz F, Becker M, Chen LX, Furst DE, Joseph-Ridge NJ, Schlesinger N, Horowitz Z, Saag K, Boice JA & Yamanaka H. Outcome measures for acute and chronic gout. J Rheumatol 32:2452-2455, 2005.
21. Schumacher HR & Chen LX: Newer therapeutic approaches: gout. Rheum Dis Clin N Am 32:235-244, 2006.
22. Schumacher HR, Becker MA, Edwards NL, Palmer WE, Macdonald PA, Palo W & Joseph-Ridge N: Magnetic resonance imaging in the quantitative assessment of gouty tophi. Int J Clin Pract 60:408-414, 2006.
23. Fang W, Zeng X, Li M, Chen LX, Schumacher HR, & Chang F: The management of gout at an academic healthcare center in Beijing: A physician survey: J Rheumatol 33:2041-2049, 2006.
24. Schlesinger N, Moore DF, Sun JD & Schumacher HR: A survey of current evaluation and treatment of gout: J Rheumatol 33:2050-2052, 2006.
25. Chen LX & Schumacher HR: Gout: can we create an evidence-based systematic approach to diagnosis and management? Best Pract Res Clin Rheumatol 20:673-684, 2006.
26. Sarawate CA, Brewer KK, Yang W, Patel PA, Schumacher HR, Saag KG, Bakst AW. Gout medication treatment patterns and adherence to standards of care from a managed care perspective. Mayo Clin Proc. 81:925-34, 2006.
27. Sarawate CA, Patel PA, Schumacher HR, Yang W, Brewer KK, Bakst AW. Serum urate levels and gout flares: analysis from managed care data. J Clin Rheumatol. 12:61-5, 2006.
28. Schumacher HR, Taylor W, Joseph-Ridge N, Perez-Ruiz F, Chen LX, Schlesinger N, Khanna D, Furst DE, Becker MA, Dalbeth N, & Edwards NL. Outcome Evaluations in Gout. J Rheumatol 34:1381-1385, 2007.
29. Taylor WJ, Schumacher HR, Singh JA, Grainger R and Dalbeth N. Assessment of outcome in clinical trials of gout: A review of current measures. Rheumatology ( Oxford) 46: 1751-1756, 2007. Epub ahead of print Aug 1, 2007.
30. Taylor WJ, Schumacher HR, Baraf HSB, et al. A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout. Ann Rheum Dis 67:888-891, 2008. Epub ahead of print November 29, 2007.
31. Schumacher HR and Chen LX. The practical management of gout. Cleveland J Med Suppl 5: S22-S25, 2008.
32. Schumacher HR, Chen, LX. Febuxostat: a viewpoint. Drugs. 68:1875-6, 2008.
33. Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, Lademacher C, Joseph-Ridge N. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 59:1540-8, 2008.
33. Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology ( Oxford). 48:188-94; 2009
34. Taylor WJ, Shewchuk R, Saag KG, Schumacher HR, Singh JA, Grainger R, Edwards NL, Bardin T, Waltrip RW, Simon LS, Burgos-Vargas R. Toward a valid definition of gout flare: results of consensus exercises using Delphi methodology and cognitive mapping. Arthritis & Rheumatism 61:535-543; 2009.
35. Terkeltaub R, Sundy JS, Schumacher HR, Murphy F, Bookbinder S, Biedermann S, Wu R, Mellis S, Radin A. The IL-1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, nonrandomized, single-blind pilot study. Ann Rheum Dis. 68:1613-7; 2009 . Epub Jul 26. 2009.
36. Becker MA, Schumacher HR, Benjamin KL, Gorevic P, Greenwald M, Fessel J, Edwards L, Kawata AK, Frank L, Waltrip R, Maroli A, Huang B; Gout Natural History Study Group, Sundy JS. Quality of life and disability in patients with treatment-failure gout. J Rheumatol. 36:1041-8; 2009. Epub Mar 30 2009.
37. Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout, J Rheumatol. 36:1273-82; 2009. Epub Mar 13 2009.
38. Schumacher HR, Taylor W, Edwards L, Grainger R, Schlesinger N, Dalbeth N, Sivera F, Singh J, Evans R, Waltrip RW, Diaz-Torne C, MacDonald P, McQueen F, Perez-Ruiz F. Outcome domains for studies of acute and chronic gout. J Rheumatol. 36:2342-5; 2009.
39. Chen LX and Schumacher HR. Febuxostat treatment for gout: what the clinican needs to know. Ther Adv Musculoskel Dis. 1:67-69; 2009.
40. Schumacher HR. Updating the management of gout. Int J Adv Rheumatol. 7: 114- 117; 2010.
41. Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, Lademacher C. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 12:R63. [Epub ahead of print]
42. Taylor WJ, Singh JA, Saag KG, Dalbeth N, Macdonald PA, Edwards NL, Simon LS, Stamp LK, Neogi T, Gaffo AL, Khanna PP, Becker MA, Schumacher HR Jr. Bringing it all together: a novel approach to the development of response criteria for chronic gout clinical trials.J Rheumatol. 38:1467-70; 2011.
43. Stamp LK, Khanna PP, Dalbeth N, Boers M, Maksymowych WP, Schumacher HR Jr, Becker MA, Macdonald PA, Edwards NL, Singh JA, Simon LS, McQueen FM, Neogi T, Gaffo AL, Strand V, Taylor WJ. Serum urate in chronic gout -- will it be the first validated soluble biomarker in rheumatology? J Rheumatol. 38:1462-6;2011.
Improved Management of Osteoarthritis
Program Summary
A series of studies are examining several aspects of therapy in controlled fashion. These include a high molecular weight hyaluronic acid for intraarticular injection into various joints, acupuncture combined with physical therapy, a Yoga-based stretching and exercise program, glucosamine and chondroitin sulfate therapy, knee bracing and foot realignment. We are examining synovial fluid crystals, cytokines and cell populations before and after interventions. We examine surgical specimens of total joint replacement with PCR to relate to care and complications. We suspect that we can identify subsets of OA that will respond to different currently available or new interventions. We investigate the role of crystals in OA. A recent study is evaluating the effect of tart cherry juice on the pain of OA.
Publications
1. Bradley JD, Flusser D, Katz BP, Schumacher HR, Brandt KD, Chambers MA and Zonay LJ:A randomized, double blind, placebo controlled trial of intravenous loading with S adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheum 21:905-911, 1994.
2. Schumacher HR:Ketoprofen extended-release capsules:A new formulation for the treatment of osteoarthritis andrheumatoid arthritis. Clinical Therapeutics 16:145-159, 1994.
3. Norden DK, Leventhal LJ, Schumacher HR: Prescribing exercise osteoarthritis of the knee. J of Musculoskeletal Medicine 11:14-21, 1994.
4. Schumacher HR: Synovial inflammation, crystals, and osteoarthritis. J Rheum 22:101-103, 1995.
5. Schumacher HR: Microvascular permeability and the effects of joint motion. Scand J Rheumatol 24:17-20, 1995.
6. Maurer BT, Moreno SI, Pickard AR, Wurst BE, Norden DK, and Schumacher HR: A comparison of recruitment methods for anosteoarthritis exercise study. Arthritis Care and Research 8:161-166, 1995.
7. Zakaoui L, Schumacher HR, Rothfuss S, Sieck M, Clayburne G: Idiopathic destructive arthropathies: Clinical, light, and electron microscopic studies. J Clin Rheumatol 2:9-17, 1996.
8. Schumacher HR, Stineman MG, Mahge S, Huppert A, Rahman M: The association between synovial fluid and treatment response in osteoarthritis. Internal Medicine 4:25-34, 1996.
9. Nanagara R, Duray PH, Schumacher HR: Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic lyme disease: Possible factors contributing to persistence of organisms. Human Pathology 27:1025—1034, 1996.
10. Park J, Schumacher HR: The clinical significance of cytoplasmic inclusions in synovial fluid examination. J of Korean Medical Science 11:326—331, 1996.
11. Gowin KM, Schumacher HR: Osteoarthritis: Practical steps to successful therapy. Consultants in Primary Care 36:2048—2059, 1996.
12. Schumacher HR, Meng Z, Sieck M, Zonay L, Clayburne G, Baker JF, Park J and Baker DG: Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis. J. Rheumatol 23:1774-1777, 1996.
13. VanLinthoudt D, Salani I, Ott H, Schumacher HR: Identification de debris cartilagineux dan le liquide synovia de genoux rhumatoides et arthrosiques. Rhumatologie (50)1:7-11, 1998.
14. Maurer BT, Stern AG, Kinossian B, Cook KD, Schumacher HR: Osteoarthritis of the knee: Isokinetic quadriceps exercise versus an educational intervention. Arch Phys Med Rehabil 80:1293-9, 1999.
15. Olmez N, Schumacher HR: Crystal deposition and osteoarthritis. Current Rheumatol Reports 1:107-11, 1999.
16. Moreno MJ, Clayburne G, Schumacher HR: Processing of noninflammatory synovial fluid is with hyaluronidase for cytospin preparations improves the accuracy of differential counts. Diagonstic Cytopathology 22:256-8, 2000.
17. Olmez N, Wang GF, Li Y, Zhang H, Schumacher HR: Chlamydial nucleic acids in synovium in osteoarthritis: what are the implications? J Rheumatol 28: 1874-1880, 2001.
18. Pullman-Mooar P, Mooar P, Sieck M, Clayburne G, Schumacher HR: Are there Distincitve Inflammatory Flares After Hylan G-F 20 Intraarticular Injections? J Rheumatol 29: 2611-2614, 2002.
19. Hillstrom H, Brower DJ, Whitnet K, McGuire J, Schumacher HR: Lower Extremity Conservative Realignment Therapies for Knee Osteoarthritis. In: Physical Medicine and Rehabilitation: State of the Art Reviews. 16:507-520, 2002.
20. Nalbant S, Martinez JAM, Kitumnuaypong T, Clayburne G, Sieck M, Schumacher HR: Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. Osteo and Cartilage 11:50-54, 2003.
21. Goldman RJ, Reinbold KA, Iglarsh A, Neustadter LM, Oatis CA, Schumacher HR: Phase I design and evaluation of an isometric muscle reeducation device for knee osteoarthritis rehabilitation. J Rehab Research Development 40:95-108, 2003.
22. Antoniou J, Tsai A, Baker D, Schumacher R, Williams GR, Iannotti JP: Milwaukee Shoulder: correlating possible etiologic variables. Clin Ortho Related Research 407:79-85, 2003.
23. Schumacher HR: Aspiration and injection therapies for joints. Arth Care and Res 49:413-420, 2003.
24. Stern AG, Moxley G, Sudha Rao TP, Disler D, McDowell C, Park M, Schumacher HR: Utility of digital photographs of the hand for assessing the presence of hand osteoarthritis. Osteoarthritis and Cartilage 12:360-365, 2004.
25. Weaton A, Borthakur A, Dodge G, Kneeland J, Schumacher HR, Reddy R: Sodium Magnetic Resonance Imaging of Proteoglycan Depetion in an In Vivo Model of Osteoarthritis. Academic Radiology, 11:21-28, 2004.
26. Schumacher HR, Paul C, Hitchon CA, El-Gabalawy H, Zonay L, Clayburne G, Sieck M, & Schwab E: Hyaluronate effects on synovium and synovial fluid. A prospective blinded study in patients with osteoarthritis of the knee. Osteoarthritis & Cartilage 14:501-503, 2006.
27. Parmelee PA, Harralson TL, Smith LA and Schumacher HR. Necessary and discretionary activities in knee osteoarthritis: do they mediate the pain-depression relationship? Pain Med 8:449-461, 2007.
28. Pessler F, Chen LX, Dia L, Gomez-Vaquero C, Diaz-Torne C, Paessler ME, Scanzello C, Cakir N, Einhorn E. and Schumacher HR. A histomorphometric analysis of synovial biopsies from individuals with Guf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheum. 27:1127-34, 2008. Epub ahead of print April 15, 2008.
29. Kwan-Morley J, Clayburne G, Schumacher HR. Synovial fluid findings in a patient after hylan GF 20 injection. J Clin Rheumatol. 14:120, 2008.
30. Parmelee PA, Harralson TL, McPherron JA, Decoster J, Schumacher HR. Pain, Disability, and Depression in Osteoarthritis: Effects of Race and Sex. J Aging Health. [Epub ahead of print] 2011 Jun 21.
Synovial Fluid, Arthrocentesis and Synovium: For Diagnosis and Examination of Drug Effects.
Program Summary
We have reported extensively on use of synovial biopsy and synovial fluid analysis for diagnosis. (see also our website at http://www.med.upenn.edu/synovium/). We have shown that even non—steroidal anti inflammatory agents affect cell populations in the joint. These may confuse interpretation of studies but effects of various drugs locally may also show critical aspects of their mechanisms of effect. In rheumatoid arthritis (RA) patients with active knee synovitis we have compared the effects of Tenidap, a LTB4 and lipoxygenase inhibitor vs piroxicam on levels of acute phase reactants (Tenidap decreases CRP), cytokines and synovial tissue cell populations, growth factors and adhesion molecules using ELISA assays and in situ hybridization. Aspirations and biopsies are done on 3 occasions in this double blind crossover study that extends our emphasis on what happens within joints. Other studies have examined the effects of the combination of misoprostol and diclofenal vs. diclofenac alone on RA joint inflammation and cytokines. Studies in OA showed that NSAIDS alone raise joint fluid TNF but that this can be blocked by addition of misoprostol. Synovial biopsies for morphology, immunohistochemistry and RT PCR are being done before and after new drugs to study the prognostic value of such biopsies. We have developed a new biopsy needle that allows important studies on small joints. We also use animal models for preliminary studies. We continue to evaluate diagnostic and classification value of joint fluid and biopsy studies and the potential value of immunohistochemistry.
Publications
1. Schumacher HR, Kulka JP: Needle biopsy of the synovial membrane: Experience with the Parker-Pearson technique. N Eng J Med 286:416-419, 1972.
2. Bahremand M, Schumacher HR: Effect of medication on synovial fluid leukocyte differentials in patients with rheumatoid arthritis. Arthritis Rheum 34:1173-1176, 1991.
3. Bulbul R, Rothfuss S, Clayburne G, Sieck M, Rao J, Saaibi DL, Schumacher HR: Studies on synovial fluid and synovium in psoriatic arthritis, effects of medication and implications for diagnosis and pathogenesis. Arthritis Rheum 38: (suppl 9) S380, 1995.
4. Saaibi DL, Park J, Schumacher HR: Developing and testing of a grading system for study of synovial pathology. Arthritis Rheum 38: (suppl 9)S328, 1995.
5. Meng ZH, Branigan P, Park J, Rao J, Baker DG, Schumacher HR: Hydroxychloroquine inhibits matrix metalloprotease production in experimental calcium pyrophosphate dihydrate crystal induced inflammation in the rat subcutaneous air pouch. Arth & Rheum 38: (suppl 9) S244, 1995.
6. Schumacher HR, Zonay L, Sieck M, Clayburne G, Baker DG: Effect of a non-steroidal anti inflammatory agent on the joint fluid composition in knee osteoarthritis. Arth & Rheum 38: (suppl 9) S240, 1995.
7. Saaibi DL, Schumacher HR: Percutaneous needle biopsy and synovial histology. In: Bird HA, Dougados M (Eds). Bailliere’s clinical rheumatology international practice and research. Imaging techniques part I: traditional methods. W.B. SaundersCompany; Philadelphia: 1996. p.535-554.
8. Ferrari AJL, Van Linthoudt D, Morrone L, Branigan P, Schumacher HR and Baker DG: Nonsteroidal anti-inflammatory drugs and prosstaglandins: Their interactions and effects on the particulate-induced inflammatory process implicated in joint implant-loosening and on monosodium urate crystal-induced inflammation. Am J of Therapeutics 3:189-194, 1996.
9. Littman BH, Schumacher HR, Boyle DL, Weisman MH and Firestein GS: Effect on tenidap on metalloproteinase gene expression in rheumatoid arthritis: A synovial biopsy study. J Clin Rheumatol 3:194-202, 1997.
10. Cheour E, Saaibi DL, Rull M, Schumacher HR: Crystal arthropathies. In: Howe HS, Feng PH (Eds). Textbook of clinical rheumatology. National Arthritis Foundation; Singapore: 1998. p. 194-206.
11. Arayssi TK, Schumacher HR: Evaluation of a modified needle for small joint biopsies. J Rheumatol 25:876-878, 1998.
12. Schumacher HR, Gerard HC, Arayssi TK, Pando JA, Branigan PJ, Saaibi DL and Hudson AP: Lower prevalence of chlamydia pneumoniae DNA compared with chlamydia trachomatis DNA in synovial tissue of arthritis patients. Arthritis Rheum 42:1889-93, 1999.
13. Fang Q, Sun YY, El- Gabalawy H, Cai W, Ko L, Chin H, Arayssi T, Schumacher HR, Williams WV: Synovial T Cell receptor heterogeneity in early arthritis. Pathbiology 67:59-74, 1999.
14. Kotake S, Schumacher HR, Arayssi TK, Gerard HC, Branigan PJ, Hudson AP, Yarboro CH, Klippel JH, Wilder RL: Gamma interferon and interleukin-10 expression in synovial tissues arthritits and undifferentiated oligoarthritis and from healthy volunteers. Infection and Immunity 67:2682- 86, 1999.
15. Moreno MJ, Clayburne G, Schumacher HR: Processing of noninflammatory synovial fluid is with hyaluronidase for cytospin preparations improves the accuracy of differential counts. Diagonstic Cytopathology 22:256-8, 2000.
16. Meng ZH, Baker DG, Branigan P, Park J, Baker S, Rao J, Schumacher HR: Hydroxychloroquine inhibits matrix metalloprotease activity in experimental calcium pyrophospate dihydratre (CPPD) crystal induced inflammation in the rat subcutaneous air pouch . Inflammopharmacology 8: 113-21, 2000.\
17. Goldbach-Mansky R, Lee JM, Hoxworth JM, Smith D 2nd, Duray P, Schumacher HR, Yaboro CH, Klippel J, Kleiner D, El- Gabalawy H: Active synovial matrix metalloproteinase- 2 is associated with radiographic erosions in patients with early synovitis. Arthritis Res 2: 145-153, 2000.
18. Singh JA, Arayssi T, Duray P, Schumacher HR: Immunohistochemistry of normal human knee synovium: a quantitative study. Ann Rheum Dis 63:785-790 2004.
19. Singh JA, Pando JA, Tomaszewski J, Schumacher HR: Quantitative analysis of immunohistologic features of very early rheumatoid synovitis in disease modifying antirheumatic drug- and corticosteroid-naïve patients. J Rheum 31:1281-1285, 2004.
20. Meador R, Hsia E, Kitumnuaypong T, Schumacher HR: TNF involvement and anti-TNF therapy of reactive and unclassified arthritis. Clin Exp Rheumatol 20: s130-134, 2002.
21. Cole BJ, Schumacher HR: Injectable corticosteroids in modern practice. J Am Acad Orthop Surg 13:37-46, 2005.
22. Shannon SE, Schumacher HR, Self S, Brown AN: Multicentric reticulohistiocytosis responding to tumor necrosis factor-α inhibition in a renal transplant patient.. J Rheum 32:565-567, 2005.
23. Zhang H, Guangping G, Clayburne G & Schumacher HR: Elimination of rheumatoid synovium in situ using a Fas Ligand ‘gene scalpel.’ Arth Res & Ther 7:R1235-R1243, 2005.
24. Schumacher HR, Chen LX: Injectable corticosteroids in treatment of arthritis of the knee. Am J Med 118:1208-14, 2005.
25. Du Y, Pullman-Mooar S & Schumacher HR: Synovial sarcoma of the foot mimicking acute gouty arthritis. J Rheumatol 32:2006-2008, 2005.
26. Pessler F, Dai L, Cron RQ & Schumacher HR: NFAT transcription factors – new players in the pathogenesis of inflammatory arthropathies? Autoimmun Rev. 5:106-10, 2006.
27. Chen LX, Schumacher HR: Current trends in crystal identification. Current Opinion in Rheumatology 18:171-173, 2006.
28. Alappatt C, Clayburne G & Schumacher HR: Concomitant polyarticular septic and gouty arthritis. J Rheumatol 33: 1707-1708, 2006.
29. Dai L, Pessler F, Chen LX, Clayburne G & Schumacher HR: Detection and initial characterization of synovial lining fragments in synovial fluid. Rheumatology ( Oxford) 45:533-537, 2006.
30. Diaz-Torne C. Schumacher HR, Yu X, Gomez-Vaquero C, Dai L, Chen LX, Clayburne G, Einhorn E, Sachdeva RM, Singh HA, Pessler F. Absence of histologic evidence of synovitis in patients with Gulf War veterans’ illness with joint pain. Arthritis Rheum 57:1316-1323, 2007.
31. Adhikesavan LG, Ayoub WT, and Schumacher HR. Misdiagnosis of a chylous cyst as chest wall gouty tophus. Arthritis Rheum 56:3854-3857, 2007. .
32. Rooney T, Bresnihan B, Andersson U, Gogarty M, Kraan M, Schumacher HR, Ulfgren AK, Veale DJ, Youssef PP, and Tak PP. Microscopic measurement of inflammation in synovial tissue: inter-observer agreement for manual quantitative, semiquantitative and computerised digital image analysis. Ann Rheum Dis 66:1656-1660, 2007.
33. Pessler F, Ogdie A, Diaz-Torne C, Dai L, Einhorn E, Schumacher HR. Subintimal Ki-67 as a synovial biomarker of inflammatory arthropathies. Ann Rheum Dis 67:162-167, 2008 Epub ahead of print July 7, 2007.
34. Schumacher HR, Chen LX, and Pessler F. Synovial biopsy in the evaluation of nonrheumatic systemic diseases causing arthritis. Curr Opin Rheumatol 20:61-65, 2008.
35. Pessler F, Chen LX, Dia L, Gomez-Vaquero C, Diaz-Torne C, Paessler ME, Scanzello C, Cakir N, Einhorn E. and Schumacher HR. A histomorphometric analysis of synovial biopsies from individuals with Guf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheum. 27:1127-34, 2008. Epub ahead of print April 15, 2008.
36. Pessler F, Dai L, Diaz-Torne C, Ogdie A, Gomez-Vaquero C, Paessler ME, Einhorn E, Chen LX, Schumacher HR. Increased angiogenesis and cellular proliferation as hallmarks of the synovium in chronic septic arthritis. Arthritis Rheum. 59:1137-46, 2008.
37. Pessler F, Dai L, Diaz-Torne C, Gomez-Vaquero C, Paessler ME, Zheng DH, Einhorn E, Range U, Scanzello C, Schumacher HR. The synovitis of “non-inflammatory” orthopaedic arthropathies: a quantitative histological and immunohistochemical analysis. Ann Rheum Dis. 67:1184-7, 2008.
38. Schumacher HR, Chen LX, Glick L. Evaluation of a knee and shoulder arthrocentesis training for primary care providers. J Rheumatol 35:2083-2084; 2008.
38. Kuipers JG, Sibilia J, Bas S, Gaston H, Granfors K, Vischer TL, Hajjaj-Hassouni N, Ladjouze-Rezig A, Sellami S, Wollenhaupt J, Zeidler H, Schumacher HR, Dougados M. Reactive and undifferentiated arthritis in North Africa: use of PCR for detection of Chlamydia trachomatis.Clin Rheumatol. Jan;28:11-6, 2009. Aug 8. 2008 [Epub ahead of print].
39. Keen HI, Bingham CO 3rd, Bradley LA, Conaghan PG, Heald AE, Kaeley GS, Maksymowych WP, Moskowitz RW, Schumacher HR Jr, Woodworth TE, Mease PJ. Assessing single joints in arthritis clinical trials.J Rheumatol. 36:2092-6; 2009.
40. Ogdie A, Li J, Dai L, Paessler ME, Yu X, Diaz-Torne C, Akmatov M, Schumacher HR, Pessler F. Identification of broadly discriminatory tissue biomarkers of synovitis with binary and multicategory receiver operating characteristic analysis.Biomarkers. 15:183-90;2010.
41. Ogdie A, Schumacher HR Jr, Dai L, Chen LX, Einhorn E, Pessler F Synovial biopsy findings in arthritis associated with hepatitis C virus infection. J Rheumatol. 37:1361-3; 2010.
Alternative Medicine
Program Summary
Non-traditional approaches to treatment have needed objective evaluation. We have been studying what documented effects can be identified from yoga, glucosamine, SAME, and herbs. We are reviewing traditional Chinese treatment for gout for the Cochrane Collaboration, comparing TCM and Western treatments and studying cherry juice in knee OA pain as well as its effect on uric acid.
Publications
1. Garfinkel MS, Schumacher HR, Husain A, Levy M, Reshetar RA: Evaluation of a yoga based regimen for treatment of osteoarthritis of the hands. J Rheumatol 21:2341-3, 1994.
2. Garfinkel MS, Singhal A, Katz WA, Allan DA, Reshetar R, Schumacher HR: Yoga-based intervention for carpal tunnel syndrome. JAMA 280:1601-1603, 1998.
3. Garfinkel M and Schumacher HR: Yoga. Rheumatic Disease Clinics of North America 26: 125-132, 2000.
4. Chen LX & Schumacher HR: West meets East in rheumatology. Curr Rheum Rpts. 7:251-253, 2005.
5. Jung SM & Schumacher HR: Can characterization by traditional Korean medical criteria help in our understanding of patients with rheumatoid arthritis? Clin Exp Rheumatol 23:729-730, 2005.
6. Kolasinski SL, Garfinkel M, Tsai AG, Matz W, Van Dyke A & Schumacher HR: Iyengar yoga for treating symptoms of osteoarthritis of the knees: a pilot study. J Alt & Comp Med 11:689-693, 2005.
7. Kolasinski SL, Garfinkel M, Tsai AG, Matz W, Van Dyke A & Schumacher HR: Iyengar yoga for treating symptoms of osteoarthritis of the knees: a pilot study. J Alt & Comp Med 11:689-693, 2005.
8. Clegg DO, Reda DJ, Harris CL, . . . Schumacher HR, et al. Glucosamine,
chondroitin sulafate, and the two in combination for painful knee
osteoarthritis. N Engl J Med 354:795-808, 2006.
9. Jung SM, Schumacher HR, Kim H, Kim M, Lee SH and Pessler F. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D 2 levels. Arthritis Res Ther 9:R64, 2007.
10. Schumacher HR. West meets East – observations on integrative medicine in rheumatology from the USA. Chin J Integr Med 14:165-166; 2008.
11. Schumacher HR. West meets East – Observations on integrative medicine in Rheumatology from the USA. Chin J Integr Med 14:165-166; 2008.
12. Jung SM, Schumacher HR, Kim H, Kim M, Lee SH and Pessler F. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D 2 levels. Arthritis Res Ther 9:R64, 2007.
Patient and Physician Education
Program Summary
A recent emphasis has been on developing and evaluating educational needs and objective results of critical education programs about gout, synovial fluid analysis and other programs. We plan to go beyond whether knowledge changes to what actual impacts are on patients. A new study is examining impact of a simplified education program on gout for primary care providers in India.
Publications
1. Fang W, Zeng X, Li M, Chen LX, Schumacher HR, Chang F: The management of gout at an academic healthcare center in Beijing: A physician survey: J Rheumatol 33:2041-2049, 2006.
2. Schlesinger N, Moore DF, Sun JD, Schumacher HR: A survey of current evaluation and treatment of gout: J Rheumatol 33:2050-2052, 2006.
3. Sarawate CA, Brewer KK, Yang W, Patel PA, Schumacher HR, Saag KG, Bakst AW. Gout medication treatment patterns and adherence to standards of care from a managed care perspective. Mayo Clin Proc. 81:925-34, 2006.
4. Schumacher HR, Taylor W, Joseph-Ridge N, Perez-Ruiz F, Chen LX, Schlesinger N, Khanna D, Furst DE, Becker MA, Dalbeth N, Edwards NL. Outcome Evaluations in Gout. J Rheumatol 34:1381-1385, 2007.
5. Schumacher HR, Chen LX, Glick L. Evaluation of a knee and shoulder arthrocentesis training for primary care providers. J Rheumatol 35:2083-2084; 2008.
6. Schumacher HR. Patient education: how can we improve it and evaluate the effects? J Clin Rheumatol. 17:229-30;2011.
7. Zhang LY, Schumacher HR, Su HH, Lie D, Dinnella J, Baker JF, Von Feldt JM. Development and evaluation of a survey of gout patients concerning their knowledge about gout. J Clin Rheumatol. 17:242-8;2011.
