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
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 evaluate
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. Recent studies from our
laboratories have found 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 making data of exact and key
initial changes difficult to assess.
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.
Program Summary
Studies from this laboratory over more than 15 years have examined the roles of cells, particles,
and associated proteins in monosodium urate crystal induced acute inflammation. 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.
Reviews have identified the paucity or controlled trials in acute or chronic gout. Attention
is now being 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 various prostheses ranging from breast implants to 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 new therapies including anti IL8, COX 2 inhibitors and herbs.
Studies are also done on two new urate lowering agents that will be alternatives in allopurinol
allergic patients. Validation of taping measurement techniques using MRI and ultrasound are being
evaluated. We are coordinating omeract and cochrane talks on evidence based diagnosis and treatment
of gout and doing database studies on gout in the VA system.
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. Hasselbacher P, Schumacher HR, Simkin PA: Gout: Applying current knowledge. Patient Care (32)10:125-139, 1998.
14. Schlesinger N, Baker DG and Schumacher HR: How well have diagnostic tests and therapies for gout been evaluated? Curr Opin Rheumatol11:441-445, 1999.
15. Olmez N, Schumacher HR: Crystal deposition and osteoarthritis. Current Rheumatol Reports 1:107-11, 1999.
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. Li- Yu J, Schumacher HR, Gratwick G: Invasive tophaceous pseudogout in the temporomandibular joint: misdiagnosis as tumor. J Clinc Rheumatol 6:272-277, 2000.
18. 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.
19. Schlesinger N, Schumacher HR: Gout: Can mangement be improved? Current Opinion in Rheumatol 13:240-244, 2001.
20. 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.
21. 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.
22. 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
23. 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.
24. 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.
25. 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.
26. Schumacher HR: Management of Gout: Why is it still difficult? New Horizons: Changing Paradigms in Primary Care 8:11-15, 2002.
27. Schlesinger N, Schumacher HR: Update on Gout. Arthitis Rheum 47: 563-565, 2002.
28. Chen LX, Schumacher HR: Gout and gout mimickers: 20 clinical pearls. J Musculo Med 20:254-258, 2003.
29. Chen LX, Schumacher HR: Diagnosis and management of gout: case study and commentary. JCOM 10:336-342, 2003.
30. 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.
31. 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.
32. Chen LX, Clayburne G, Schumacher HR: Update on identification of pathogenic crystals in joint fluid. Cur Rheum Rep 6:217-220, 2004.
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.
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.
Program Summary
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 recent studies examine the effects of the combination of misoprostol
and diclofenal vs. diclofenac alone on RA joint inflammation and cytokines.
Recent data from 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
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.
Publications
1. Bahremand M, Schumacher HR: Effect
of medication on synovial fluid leukocyte differentials in patients with
rheumatoid arthritis. Arthritis Rheum 34:1173-1176, 1991.
2. 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.
3. 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.
4. 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.
5. 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.
6. Arayssi TK, Schumacher HR: Evaluation of a modified needle for small joint biopsies. J Rheumatol 25:876-878, 1998.
7. 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.
8. 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.
9. 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.
10. 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.\
11. 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.
12. Singh JA, Arayssi T, Duray P, Schumacher HR: Immunohistochemistry of normal human knee synovium: a quantitative study. Ann Rheum Dis 63:785-790 2004.
13. 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.
14. 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.
Program Summary
We are using magnetic resonance to study diagnosis and pathogenesis of
osteoarthritis (OA). Using a small coil we are comparing the sensitivity
of MRI with histology in detecting small changes in patellar cartilage
in hopes that this will be a technique to detect early improvement or
deterioration in cartilage after therapy. In these collaborations with
Ravinder Reddy we are studying the use of proton and sodium MR image of
cartilage to search for way to monitor drug effects in OA and RA.
Publications
1. Baker DG, Schumacher HR and Wolf GL: Nuclear magnetic resonance evaluation
of synovial fluid and articular tissue. J Rheumatol 12:1062-1065, 1985.
2. Keenan GF, Paul CR, Lenkinski RE, Wehrli SL, Schumacher HR: High resolution proton magnetic resonance spectroscopy in the analysis of synovial fluid from children with JRA. Arth & Rheum 38: (suppl 9) S286, 1995.
3. Paul CR, Brower D, Lenkinski RE, Keenan G, Wherli S, Schumacher HR. Proton NMR spectroscopy studies of osteoarthritic synovial fluids show changes after intraarticular hyalinonic acid. Arth Rheum 4?S146, 1998 (Suppl.)
4. 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.