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(ization with a human heat shock peptide responsible for)Tj
-0.0157 Tw 0 -1.2 TD
(uveitis in rats was suggested as a possible strategy for future)Tj
0.02499 Tw T*
[(treatment of BD by )17.7 (T)74 (. Lehner)54.8 (.)]TJ
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(The conference provided a good opportunity for all)Tj
0.0843 Tw -1.2 -1.2 Td
(participants from silk route and non-silk route countries to)Tj
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(discuss recent data and results against a background of)Tj
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(current theories of the etiopathogenesis of BD. It is antici-)Tj
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[(pated that the International Society for Beh\215et\325)54.8 (s Disease will)]TJ
0.26379 Tw T*
[(further promote interest and studies in the disease. )17.7 (The)]TJ
0.0965 Tw T*
[(T)69.9 (enth International Congress on BD is planned for Berlin,)]TJ
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[(Germany)64.9 (, in 2002.)]TJ
/T1_1 1 Tf
-0.00011 Tc 0 Tw 10.1 -2.4 Td
[(MICHAEL)-220.2 (SCHIRMER,)]TJ
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(MD,)Tj
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(Department of Internal Medicine,)Tj
0 -1.25 TD
[(Innsbruck University)64.8 (, Innsbruck, )54.8 (Austria;)]TJ
/T1_1 1 Tf
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[(KENNETH T)73.9 (. )-17.7 (CALAMIA,)]TJ
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(MD,)Tj
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(Assistant Professor of Medicine,)Tj
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(Mayo Clinic Jacksonville,)Tj
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(4500 San Pablo Road,)Tj
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(Jacksonville, Florida 32224, USA; )Tj
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(E-mail: Calamia@mayo.edu)Tj
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(HANER DIRESKENELI,)Tj
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(MD,)Tj
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[(Associate Professor of Rheumatology)64.8 (,)]TJ
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(University of Marmara Medical School,)Tj
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[(Istanbul, T)35 (urkey)64.9 (.)]TJ
/T1_2 1 Tf
0.02499 Tw -12.625 -2.5 Td
[(Addr)36.8 (ess r)36.8 (eprint r)36.8 (equests to Dr)110.7 (. Calamia.)]TJ
0.2339 Tw 0 -2.75 TD
[(Meeting pr)36.8 (esenters in or)36.8 (der of first mention)]TJ
/T1_0 1 Tf
18.8812 0 Td
[(: S. Lee, )54.8 (Ajou University)64.8 (,)]TJ
0 Tc 0.0246 Tw -18.8812 -1.25 Td
[(Suwon, Kyonggi, Korea; Ch. C. Zouboulis, )17.8 (The Free University of Berlin,)]TJ
-0.00011 Tc -0.01669 Tw 0 -1.25 TD
[(Berlin, Germany; G. )54.9 (Azizleri, Istanbul University)64.8 (, Istanbul, )17.8 (T)35 (urkey; J. Roh,)]TJ
0.24741 Tw T*
[(Y)99.8 (onsei University)64.8 (, Seoul, Korea; K. Sharquie, University of Baghdad,)]TJ
-0.0269 Tw T*
(Baghdad, Iraq; K. Calamia, Mayo Clinic, Jacksonville, Florida, USA; M.A.\
)Tj
0.0705 Tw T*
[(Chamberlain, University of Leeds, Leeds )17.7 (W)79.9 (est )36.8 (Y)99.8 (orkshire, UK; N. Dilsen,)]TJ
0.00751 Tc 0.3674 Tw T*
[(Istanbul University; R. )17.6 (T)35 (unc, University of Istanbul; N. Goksugur)39.6 (,)]TJ
-0.00011 Tc 0.11929 Tw T*
[(University of Istanbul, Istanbul, )17.7 (T)35 (urkey; S. Benamour)39.7 (, University of Ibn)]TJ
0.064 Tw 33 47.671 Td
[(Rochd, Casablanca, Morocco; F)79.7 (. Shahram, )17.7 (T)69.9 (ehran University for Medical)]TJ
0.0056 Tc 0.36929 Tw T*
[(Sciences, )17.8 (T)69.9 (ehran, Iran; M. Melikoglu, Istanbul University)65.1 (, Istanbul,)]TJ
-0.00011 Tc 0.3237 Tw T*
[(T)35 (urkey; R. S. Rogers, Mayo Clinic, Rochester)39.7 (, Minnesota, USA; C.)]TJ
0.0098 Tw T*
[(Chams-Davatchi, )17.7 (T)69.9 (ehran University for Medical Sciences, )17.7 (T)69.9 (ehran, Iran; C.)]TJ
0.1348 Tw T*
[(Durusoy)64.8 (, )54.8 (Akdeniz University)64.8 (, )54.8 (Antalya, )17.7 (T)35 (urkey; S. Kucukoglo; I. Fresko,)]TJ
0.04311 Tw T*
[(Istanbul University)64.8 (, Istanbul, )17.7 (T)35 (urkey; H-Y)128.8 (. )54.8 (Ahn, )36.7 (Y)99.8 (onsei University)64.8 (, Seoul,)]TJ
0.0455 Tw T*
[(Korea; F)79.7 (. Davatchi, )17.7 (T)69.9 (ehran University for Medical Sciences, )17.7 (T)69.9 (ehran, Iran;)]TJ
0.0946 Tw T*
[(C.G Barnes, )17.8 (The Royal London Hospital, London, UK; )54.9 (A. Nadji, )17.8 (T)69.9 (ehran)]TJ
-0.0103 Tw T*
[(University for Medical Sciences, )17.8 (T)69.9 (ehran, Iran; E. Kaklamani, University of)]TJ
0.25459 Tw T*
[(Athens, )54.8 (Athens, Greece; B. )17.7 (W)79.9 (echsler)39.7 (, Pitie-Salpetriere and St )54.8 (Antoine)]TJ
0.3584 Tw T*
[(Hospitals, Paris, France; F)79.7 (. Khosravi, Shiraz University for Medical)]TJ
0.0343 Tw T*
[(Sciences, Shiraz, Iran; J. Grana, Juan Canalejo Hospital, )54.8 (A)-229.4 (Coruna, Spain;)]TJ
0.0547 Tw T*
[(N. Ohya, St Marianna University)64.9 (, Kanagawa, Japan; L. Emmi, University)]TJ
0.12849 Tw T*
[(of Florence, Firenze, Italy; )36.7 (Y)110.8 (-M. Kang, Kyungpook National University)64.8 (,)]TJ
-0.02251 Tw T*
[(T)69.9 (aegu, Korea; )17.8 (W)91.8 (. Kim; N. Kim; C.R. Lee, )36.8 (Y)99.8 (onsei University)64.8 (, Seoul, Korea;)]TJ
0.0199 Tc 0.4722 Tw T*
[(A. )54.8 (Al-Dalaan, King Faisal Hospital, Riyadh, Saudi )55 (Arabia; Sh.)]TJ
-0.00011 Tc 0.29311 Tw T*
(Samangooei, Shiraz University for Medical Sciences, Shiraz, Iran; S.)Tj
0.0657 Tw T*
[(Ohno, )36.8 (Y)99.8 (okohama City University)64.8 (, )36.8 (Y)99.8 (okohama, Japan; I. Kotter)39.7 (, University)]TJ
0.31441 Tw T*
[(of )17.7 (T)35 (ubingen, )17.7 (T)35 (ubingen, Germany; )54.8 (A. Gul, University of Manchester)39.7 (,)]TJ
0.24809 Tw T*
[(Manchester)39.7 (, UK; C-S. Cho, )17.7 (The Catholic University of Korea, Seoul,)]TJ
0.0903 Tw T*
[(Korea; J. Duymaz, University of Istanbul, Istanbul, )17.8 (T)35 (urkey; )17.8 (W)91.9 (. Madanet,)]TJ
0.2605 Tw T*
[(The Jordan Hospital, )54.8 (Amman, Jordan; Ji-W)91.7 (. Mok, Sungshin )17.7 (W)79.9 (omen\325)54.8 (s)]TJ
0.0199 Tc 0.42081 Tw T*
[(University)64.9 (, Seoul, Korea; I. )17.8 (T)69.9 (ouitou, Hospital )54.9 (A. de )17.7 (V)59.8 (illeneuve,)]TJ
-0.00011 Tc 0.1937 Tw T*
[(Montpellier)39.7 (, France; )17.8 (T)74 (. Lehner)39.7 (, Guy\325)54.8 (s, King\325)54.8 (s & St. )17.7 (Thomas\325)-369.8 (Hospital,)]TJ
0.19659 Tw T*
[(London, UK; H. Direskeneli, Marmara University)64.8 (, Istanbul, )17.8 (T)35 (urkey; E.)]TJ
0.00169 Tc 0.3732 Tw T*
[(Isogai, Sapporo Medical University)64.8 (, Sapporo, Japan; S. Sohn, )54.7 (Ajou)]TJ
-0.00011 Tc 0.1931 Tw T*
[(University)64.9 (, Suwon, Kyonggi, Korea; M. Ben )54.8 (Ahmet, Institu Pasteur de)]TJ
-0.06799 Tw T*
[(T)35 (unis, )-37.1 (T)35 (u)-0.1 (nis, )-37.1 (T)35 (unisia; )-54.8 (S. Assaad-Khalil, Alexandria )-54.8 (University)64.8 (, Alexandria,)]TJ
0.02209 Tw T*
[(Egypt; J. Katsantonis, )17.7 (The Free University of Berlin, Berlin, Germany; M.)]TJ
0.2421 Tw T*
[(A)91.8 (ygunduz, Suleyman Demirel University)64.8 (, Izmir; N. Bozkurt, Marmara)]TJ
0.00639 Tc 0.3685 Tw T*
[(University)64.8 (, Istanbul, )17.7 (T)35 (urkey; D.O. Haskard, Hammersmith Hospital,)]TJ
-0.00011 Tc 0.12601 Tw T*
[(London, UK; H. Cho, )36.8 (Y)99.8 (onsei University)64.8 (, Seoul, Korea; )17.8 (V)128.9 (. Hamuryudan,)]TJ
0.1862 Tw T*
[(University of Istanbul, Istanbul; )54.8 (A. Boyvat, )54.9 (Ankara University)64.8 (, )54.8 (Ankara,)]TJ
0.0551 Tw T*
[(T)35 (urkey; N. Stubiger)39.7 (, University Medical Schools, )17.7 (T)35 (ubingen, Germany; R.)]TJ
0.2043 Tw T*
[(Karkhaneh, )17.7 (T)69.9 (ehran University for Medical Sciences, )17.7 (T)69.9 (ehran, Iran; )36.7 (Y)110.8 (-)0.3 (T)73.9 (.)]TJ
0.048 Tw T*
[(Kwak, )36.8 (Y)99.8 (onsei University)64.8 (, Seoul, Korea; Z. Zhuoli, Peking Union Medical)]TJ
0.1427 Tw T*
[(Hospital, Beijing, China; C.W)91.7 (. Lee, )17.7 (W)79.9 (allace Memorial Baptist Hospital,)]TJ
0.02499 Tw T*
(Seoul, Korea.)Tj
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\251 2001. All rights reserved.)Tj
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(Downloaded on March 29, 2024 from )Tj
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(The Journal of Rheumatology 2001; 28:3)Tj
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(higher risk also in homozygotes \(relative risk 6.1\) \(Cho\). In)Tj
0.19901 Tw 0 -1.2 TD
(other studies for genetic markers, no associations of BD)Tj
0.1098 Tw T*
(with tumor necrosis factor alpha \(TNF-)Tj
/T1_2 1 Tf
0 Tc 0 Tw [-0.3 (\002)]TJ
/T1_1 1 Tf
-0.00011 Tc 0.10989 Tw [0.1 (\) or interleukin 6)]TJ
0.34 Tw T*
(\(IL-6\) gene promoter regions were observed \(Duymaz,)Tj
0.0947 Tw T*
[(Gul\); however)39.7 (, a weak association with intercellular adhe-)]TJ
0.02901 Tw T*
(sion molecule-1 E469 gene polymorphism was found \(rela-)Tj
0.21741 Tw T*
[(tive risk 2.1\) \(Madanat\). )54.9 (Another association with )17.8 (T)79.9 (AP2)]TJ
0.22861 Tw T*
(\(transporter associated with antigen processing 2\) genes,)Tj
0.3275 Tw T*
(which have an essential role in the antigen presenting)Tj
0.18581 Tw T*
[(system, was also reported from Korea with )17.8 (T)79.9 (AP2*A/*A,)]TJ
-0.0018 Tw T*
[(T)79.9 (AP2*C/*C, and )17.8 (T)79.9 (AP2*A/*C frequencies increased \(Mok\).)]TJ
0.258 Tw T*
[(Finally)64.8 (, some familial Mediterranean fever related pyrin)]TJ
0.0018 Tc 0.37309 Tw T*
(mutations \(E148Q and P706\) were found with higher)Tj
-0.00011 Tc 0.05991 Tw T*
(frequency in patients with BD, suggesting that pyrin muta-)Tj
0.26469 Tw T*
(tions may act as additional susceptibility factors in BD)Tj
-0.0002 Tc 0 Tw T*
[(\(T)69.6 (ouitou\).)]TJ
-0.00011 Tc -0.01019 Tw 1.2 -1.21 Td
[(On this genetic background, )17.8 (T)74 (. Lehner summarized some)]TJ
0.22771 Tw -1.2 -1.21 Td
(of the possible immunopathogenetic mechanisms in BD.)Tj
0.0289 Tw 0 -1.21 TD
(Microbial or other stress factors might stimulate heat shock)Tj
-0.0235 Tw T*
[(proteins \(HSP\) and MICA)-171.7 (gene products, resulting in signif-)]TJ
0.07111 Tw T*
(icant upregulation of )Tj
/T1_2 1 Tf
-0.0002 Tc 0 Tw [-0.5 (\003\004)]TJ
/T1_1 1 Tf
-0.00011 Tc 0.05341 Tw [-0.2 (+ T)-303.3 (cells. These T)-303.3 (cells )-17.7 (might )-17.7 (then)]TJ
0.11259 Tw T*
(generate a number of \247-chemokines, functioning as innate)Tj
0.0199 Tc 0.5135 Tw T*
(adjuvants, enhancing cellular and humoral immune)Tj
-0.00011 Tc 0.2108 Tw T*
(responses by the mucosal as well as the systemic route.)Tj
0.0023 Tw T*
[(T)69.9 (ogether with IL-12, \247-chemokines induce )17.8 (Th1 polarization)]TJ
0.09599 Tw T*
(in BD. Stimulation of peripheral lymphocytes with human)Tj
0.07629 Tw T*
(HSP60 immunodominant peptides increased CD3+, )Tj
/T1_2 1 Tf
0 Tc 0 Tw 21.3859 0 Td
(\002)Tj
/T1_1 1 Tf
0.0584 Tw [0.1 (\247+ T)]TJ
-0.00011 Tc 0.26891 Tw -21.3859 -1.21 Td
[(cell receptor positive )17.7 (T)-501 (cells, whereas bacterial extracts)]TJ
0 Tc 0 Tw T*
(\()Tj
/T1_0 1 Tf
-0.00011 Tc 0.0027 Tw [0.2 (Str)36.8 (eptococcus sanguis)]TJ
/T1_1 1 Tf
0 Tw 9.4659 0 Td
(and )Tj
/T1_0 1 Tf
0.0027 Tw 1.6965 0 Td
(Escherichia coli)Tj
/T1_1 1 Tf
[-0.1 (\) caused a more)]TJ
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(cytotoxic pattern, suggesting that innate immunity is)Tj
-0.00011 Tc 0.23779 Tw T*
(possibly also activated \(Direskeneli\). In an experimental)Tj
0.03951 Tw T*
(mouse model, heat shock to oral mucosal surface increased)Tj
-0.0107 Tw T*
(the colonization of )Tj
/T1_0 1 Tf
0 Tc [-0.4 (S. sanguis.)]TJ
/T1_1 1 Tf
-0.00011 Tc 12.2494 0 Td
(Inflammatory cytokines were)Tj
0.0472 Tw -12.2494 -1.21 Td
(detected in the mucosa and a mild neutrophil infiltration of)Tj
0.0076 Tc 0.36729 Tw T*
(the eye was observed. Granulocyte colony-stimulating)Tj
-0.00011 Tc 0.0262 Tw T*
(factor transgenic mice also had more severe disease after )Tj
/T1_0 1 Tf
0 Tc 0 Tw [-0.4 (S.)]TJ
-0.00011 Tc T*
(sanguis)Tj
/T1_1 1 Tf
-0.03641 Tw 3.2692 0 Td
[(inoculation \(Isogai\). )54.9 (As G-CSF is a priming agent of)]TJ
0.23129 Tw -3.2692 -1.21 Td
(neutrophils, hypersecretion of proinflammatory cytokines)Tj
0.022 Tw T*
(due to possible genetic defects could be another contributor)Tj
0.3423 Tw T*
(to unregulated inflammation in BD. In another animal)Tj
-0.0302 Tw T*
(model, herpes simplex virus inoculation of ICR mice did not)Tj
0.2791 Tw T*
(develop BD when macrophages were knocked out, and)Tj
0.0392 Tw T*
[(induction of )17.8 (Th2 cytokine production attenuated BD symp-)]TJ
0.0271 Tw T*
[(toms, suggesting that )17.7 (Th1 cytokines drive the inflammation)]TJ
0.27071 Tw T*
[(\(Sohn\). )17.7 (Th1 cytokines interferon-)]TJ
/T1_2 1 Tf
0 Tc 0 Tw [-0.3 (\003)]TJ
/T1_1 1 Tf
-0.00011 Tc 0.27071 Tw 15.1648 0 Td
(and IL-12 were also)Tj
0.0199 Tc 0.37289 Tw -15.1648 -1.21 Td
[(increased in patients\325)-569 (sera, but the antiinflammatory)]TJ
-0.00011 Tc 0.22729 Tw T*
[(cytokines IL-10 and transforming growth factor)19.7 (-\2471 were)]TJ
0.02499 Tw T*
[(also elevated \(Ben )54.8 (Ahmet, )54.8 (Assaad-Khalil\).)]TJ
0.233 Tw 1.2 -1.2 Td
(Elevated IL-8 levels were found in BD patients with)Tj
-0.0083 Tw -1.2 -1.2 Td
(active disease and in human endothelial cells in culture with)Tj
0.0741 Tw 0 -1.2 TD
[(Beh\215et\325)54.8 (s sera. IL-8 production by these cells was inhibited)]TJ
0.1554 Tw T*
(by agents used in the treatment of the disease, especially)Tj
-0.0002 Tc 0 Tw T*
(interferon-)Tj
/T1_2 1 Tf
0 Tc 4.2744 0 Td
(\002)Tj
/T1_1 1 Tf
-0.00011 Tc 0.2159 Tw [0.1 (-2a and cyclosporin )54.9 (A)-410.9 (\(Zouboulis\). IL-8 was)]TJ
0.0199 Tc 0.44991 Tw -4.2744 -1.2 Td
(suggested as a reliable marker for disease activity)Tj
-0.00011 Tc 0.144 Tw 26.4 63.92 Td
(\(Katsantonis\). In a search for other laboratory markers of)Tj
0.01331 Tc 0.3616 Tw T*
(disease, \247)Tj
0 Tc 0 Tw 6.5 0 0 6.5 361.8258 697.8616 Tm
(2)Tj
0.01331 Tc 0.3616 Tw 10 0 0 10 365.1627 701.1616 Tm
[(-microglobulin and serum amyloid )54.7 (A)-570.1 (were)]TJ
0.00639 Tc 0.3685 Tw -4.7163 -1.2 Td
(suggested to have higher sensitivity in active disease)Tj
-0.00011 Tc 0.1129 Tw T*
(\(70\32080%\) compared to erythrocyte sedimentation rate and)Tj
0.1235 Tw T*
[(C-reactive protein \(20\32035%\) \(A)91.7 (ygunduz\). Serum levels of)]TJ
0 Tw T*
(another )Tj
/T1_2 1 Tf
0 Tc 3.4141 0 Td
(\002)Tj
/T1_1 1 Tf
-0.00011 Tc 0.1658 Tw [0.1 (-chemokine, GRO-)]TJ
/T1_2 1 Tf
0 Tc 0 Tw [-0.3 (\002)]TJ
/T1_1 1 Tf
-0.00011 Tc 0.1658 Tw [0.1 (, and \247-chemokines MCP-1)]TJ
0.02499 Tw -3.414 -1.2 Td
(and RANTES were also elevated \(Bozkurt\).)Tj
0.12711 Tw 1.2 -1.2 Td
(D.O. Haskard showed that administration of vitamin C)Tj
0.0331 Tw -1.2 -1.2 Td
(increased flow mediated dilatation in BD, rapidly reversing)Tj
0.04601 Tw T*
[(vascular endothelial dysfunction. )17.7 (These results suggest that)]TJ
0.1795 Tw T*
(vascular endothelial dysfunction might be due to oxidant)Tj
0.1523 Tw T*
(stress. Direct activation of endothelial cells was observed)Tj
0.17731 Tw T*
(with IgM antiendothelial cell antibodies through intracel-)Tj
0.29111 Tw T*
(lular protein kinases and induced expression of surface)Tj
0.02499 Tw T*
(intercellular adhesion molecule-1 \(Cho\).)Tj
/T1_3 1 Tf
0 -2.4 TD
[(MANAGEMENT)-202.4 (AND NEW)-239.4 (THERAPEUTIC)]TJ
0 Tw 0 -1.2 TD
(APPROACHES)Tj
/T1_1 1 Tf
0.01871 Tw 0 -1.21 TD
[(S. )54.8 (Assaad-Khalil recognized that the ideal therapy of ocular)]TJ
0.0182 Tw T*
(manifestations is not at hand, and combination therapy may)Tj
0.0209 Tw T*
[(be more beneficial. )17.7 (The therapeutic choice must be individ-)]TJ
0.0246 Tw T*
(ualized and guided by accurate ophthalmologic assessment.)Tj
0.345 Tw T*
(Several therapeutic approaches for ocular disease were)Tj
0.31841 Tw T*
[(presented. \(1\) F)79.7 (. Davatchi reported an improvement of)]TJ
0.0108 Tc 0.36411 Tw T*
(visual acuity with pulse cyclophosphamide and pred-)Tj
-0.00011 Tc 0.0703 Tw T*
(nisolone compared to prednisolone alone in a double blind)Tj
-0.0108 Tw T*
[(crossover study)64.8 (, whereas inflammatory indexes improved in)]TJ
0.08051 Tw T*
(both groups. \(2\) Combination therapy with low dose pulse)Tj
0.05701 Tw T*
(cyclophosphamide and methotrexate was superior to single)Tj
0.2079 Tw T*
(therapy with the same drugs \(Shahram\). \(3\) Experiences)Tj
0.0179 Tc 0.35699 Tw T*
(were expanded regarding treatment with interferon-)Tj
/T1_2 1 Tf
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(\002)Tj
/T1_1 1 Tf
-0.00011 Tc 0.1297 Tw -23.3692 -1.21 Td
(\(Kotter\), in combination with azathioprine \(Hamuryudan\),)Tj
0.10159 Tw T*
(with high dose corticosteroids at induction \(Adler\), and in)Tj
0.1179 Tw T*
[(disease resistant to immunosuppressive agents \(W)79.7 (echsler\).)]TJ
0.06911 Tw T*
(Longterm remissions were seen in ocular disease \(Koetter\))Tj
0.18381 Tw T*
(and in the treatment of mucocutaneous disease \(Boyvat\).)Tj
0.01221 Tc 0 Tw T*
(Interferon-)Tj
/T1_2 1 Tf
0 Tc [0.3 (\002)]TJ
/T1_1 1 Tf
0.01221 Tc 0.3627 Tw 5.7332 0 Td
[(may af)17.7 (fect cytokine networks, especially)]TJ
-0.00011 Tc 0.1308 Tw -5.7331 -1.21 Td
[(through soluble )17.7 (TNF receptor p75 \(Direskeneli\), and may)]TJ
0.0005 Tc 0.3744 Tw T*
[(inhibit retinal angiogenesis \(Stuebiger\). )17.6 (The chance of)]TJ
0.0199 Tc 0.62601 Tw T*
(improving vision after vitrectomy appears limited)Tj
-0.00011 Tc 0 Tw T*
(\(Karkhaneh\).)Tj
0.0741 Tw 1.2 -1.2 Td
(Thalidomide was found to be useful in one patient with)Tj
0.0062 Tc 0.3687 Tw -1.2 -1.2 Td
(recurrent episodes of intestinal disease \(Hamuryudan\).)Tj
-0.00011 Tc 0.1322 Tw 0 -1.2 TD
[(Thalidomide tends to decrease )17.7 (TNF-)]TJ
/T1_2 1 Tf
0 Tc 0 Tw [-0.1 (\002)]TJ
/T1_1 1 Tf
-0.00011 Tc 0.1322 Tw 16.1846 0 Td
(receptor levels and)Tj
0.0791 Tw -16.1846 -1.2 Td
[(CD8/CD1)36.8 (1\247+ )17.7 (T)-311.3 (cells and natural killer cells in early treat-)]TJ
0.0544 Tw T*
[(ment, and increases CD4+CD45RO+ memory )17.7 (T)-286.5 (and )]TJ
/T1_2 1 Tf
-0.0002 Tc 0 Tw 21.6338 0 Td
(\003\004)Tj
/T1_1 1 Tf
0 Tc 0.03661 Tw [-0.2 (+ T)]TJ
-0.00011 Tc 0.04111 Tw -21.6338 -1.2 Td
(cells later in BD \(Direskeneli\). Mycophenolate mofetil was)Tj
0.13969 Tw T*
(not helpful in a small number of patients with mucocuta-)Tj
0.27901 Tw T*
(neous disease \(Zouboulis\). Dapsone was reported to be)Tj
0.02499 Tw T*
(helpful in several disease manifestations \(Sharquie\).)Tj
0.0883 Tw 1.2 -1.2 Td
(Aggressive medical management should be given when)Tj
0.3336 Tw -1.2 -1.2 Td
[(sur)17.7 (gery for aneurysm or valve replacement is required)]TJ
0.16051 Tw T*
(\(Kwak, Zhuoli, Lee\) to reduce mortality and recurrences.)Tj
0.0262 Tw T*
[(Finally)64.8 (, as a less toxic, immunomodulatory approach, toler-)]TJ
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[(CLINICAL)-220.2 (MANIFEST)73.9 (A)74 (TIONS)]TJ
/T1_1 1 Tf
0.0199 Tc 0.424 Tw 0 -1.21 TD
(Oral aphthous ulcers \(92\320100%\), genital ulcerations)Tj
0.72279 Tw T*
(\(57\32093%\), skin lesions \(38\32099%\), ocular lesions)Tj
0.39571 Tw T*
(\(29\320100%\), and arthropathy \(16\32084%\) are the most)Tj
-0.00011 Tc 0.3024 Tw T*
[(frequent clinical features of BD. )17.7 (The presence of oral,)]TJ
0.1674 Tw T*
[(ocular)39.7 (, and/or genital lesions, however)39.7 (, can also occur in)]TJ
0.0042 Tc 0.3707 Tw T*
(patients with erythema multiforme, mucous membrane)Tj
-0.00011 Tc 0.05209 Tw T*
(pemphigoid, and the vulvovaginal-gingival form of erosive)Tj
-0.0217 Tw T*
[(lichen planus. )54.8 (As all 3 conditions may be confused with BD,)]TJ
-0.009 Tw T*
[(R.S. Rogers III referred to them as pseudo-Beh\215et\325)54.8 (s disease.)]TJ
0.3347 Tw T*
(The variable clinical features of the skin lesions were)Tj
0.15469 Tw T*
[(emphasized in several reports. )17.7 (T)69.9 (ypical acne was no more)]TJ
-0.0117 Tw T*
(frequent in BD than in controls, and should be distinguished)Tj
0.34351 Tw T*
(from the pustulosis \(pseudofolliculitis\) of BD \(Chams-)Tj
0.29581 Tw T*
[(Davatchi\). However)39.7 (, androgen receptors were higher in)]TJ
0.0562 Tw T*
(papulopustular lesions in BD than controls, suggesting that)Tj
0.0071 Tw T*
(these may play a role in these lesions \(Durusoy\). Cutaneous)Tj
0.14909 Tw T*
(ultrasound was highly specific in distinguishing erythema)Tj
0.0199 Tc 0.65021 Tw T*
(nodosum lesions from superficial thrombophlebitis)Tj
-0.00011 Tc 0.26511 Tw T*
(\(Kucukoglu\). Perigenital and anal aphthous lesions may)Tj
0.00481 Tc 0.0531 Tw T*
[(occur)39.6 (, especially in children \(Zouboulis\) and epididymitis,)]TJ
0.20711 Tw T*
(orchitis, prostatitis, and ovarian cysts are seen in a few)Tj
0.1254 Tw T*
[(patients. )17.8 (The positivity of the pather)17.8 (gy test varies widely)]TJ
0.2767 Tw T*
(\(6\32071%\), but according to N. Dilsen it should still be)Tj
-0.0258 Tw T*
(applied to every patient more than once, with 2 thick needle)Tj
-0.0034 Tw T*
(pricks \(20\32022 gauge\), read at 48 hours. I. Fresko reported a)Tj
0.2003 Tw T*
[(greater sensitivity \(78% compared to 28% for pather)17.9 (gy\))]TJ
0.1545 Tw T*
(and a better reproducibility by measurement of the cuta-)Tj
-0.0033 Tw T*
(neous response to the intradermal injection of monosodium)Tj
0.2224 Tw T*
[(urate crystals than with the pather)17.8 (gy test. )54.9 (A)-422.4 (concordant)]TJ
0.19701 Tw T*
(response was observed in 95% of the patients after one)Tj
0.00369 Tw T*
[(year)54.8 (. )54.8 (An oral pather)17.8 (gy test was found to have similar sensi-)]TJ
0.0961 Tw T*
(tivity to the skin test in Iraqi patients with BD \(Shaquie\).)Tj
0.1615 Tw T*
(Local irritating factors were found to play a role in oral)Tj
0.2881 Tw T*
(aphthosis, especially of the anterior tongue and buccal)Tj
0.02499 Tw T*
(mucosa \(Ahn\).)Tj
-0.00011 Tc 0.0522 Tw 1.2 -1.2 Td
(Blindness is frequent in BD in Morocco \(S. Benamour\),)Tj
0.0014 Tw -1.2 -1.2 Td
(the main cause being lack of early and correct management.)Tj
0.1006 Tw 0 -1.2 TD
[(F)79.8 (. Davatchi reported that the outcome of the eyes was not)]TJ
-0.01289 Tw T*
(correlated to the duration of the lesions, as long as treatment)Tj
0.00819 Tw T*
(was pursued during active disease and cytotoxic drugs were)Tj
0.02499 Tw T*
[(changed in case of inef)17.7 (fectiveness.)]TJ
0.00751 Tw 1.2 -1.2 Td
(According to C.G. Barnes, the prevalence of arthritis has)Tj
-0.013 Tw -1.2 -1.2 Td
(been shown to be 45\32050%, with an even higher incidence of)Tj
0.10741 Tw T*
[(arthralgia. )17.7 (The arthritis may be oligoarticular or polyartic-)]TJ
0.1615 Tw T*
[(ular)39.7 (, intermittent or chronic, with knee involvement most)]TJ
0.0199 Tc 0.4211 Tw T*
(typical. It does not regularly include sacroiliitis or)Tj
-0.00011 Tc 0.07719 Tw T*
(spondylitis and should not be classified with the seronega-)Tj
0.06149 Tw T*
(tive spondyloarthropathies, yet the incidence of ankylosing)Tj
0.0061 Tw T*
(spondylitis was found to be higher than in the control popu-)Tj
0.16 Tw T*
(lation \(not given\) in Iran \(Nadji\). Unusual manifestations)Tj
0.0199 Tc 0.52361 Tw T*
[(include a deforming or erosive arthropathy)65 (. )54.9 (Acute)]TJ
-0.00011 Tc 0.0197 Tw T*
(monoarthritis, myalgia, myositis, bone infarction, and avas-)Tj
0.1452 Tw T*
(cular osteonecrosis were much less common \(Benamour\).)Tj
0.07941 Tw 26.4 63.95 Td
[(T)69.9 (wo studies pointed to the association of arthritis and skin)]TJ
0.02499 Tw T*
[(lesions \(T)34.8 (un\215, Kaklamani\).)]TJ
0.00369 Tw 1.2 -1.2 Td
(The French experience with dural sinus thrombosis in 36)Tj
0.1306 Tw -1.2 -1.2 Td
[(patients was presented \(W)79.7 (echsler\). )17.7 (T)35 (reatment consisted of)]TJ
0.0199 Tc 0.3952 Tw T*
(anticoagulants, corticosteroids, and colchicine in the)Tj
0.01019 Tc 0.3647 Tw T*
[(majority)64.8 (, with immunosuppressives reserved for those)]TJ
-0.00011 Tc -0.0069 Tw T*
(patients with uveitis or central nervous system involvement.)Tj
0.37421 Tw T*
(The prognosis of treated patients was generally good.)Tj
0.2789 Tw T*
(Central nervous system involvement was the presenting)Tj
-0.002 Tw T*
(manifestation of BD in 5 patients out of 15 with the compli-)Tj
0.0649 Tw T*
(cation in Shiraz in southwestern Iran \(Khosravi\). Magnetic)Tj
0.02229 Tw T*
(resonance image \(MRI\) scanning was confirmed as a sensi-)Tj
0.263 Tw T*
(tive test in neuro-Beh\215et. Subclinical MRI lesions were)Tj
0.1339 Tw T*
(found in some BD patients that did not evolve to clinical)Tj
0.1683 Tw T*
(disease \(Grana\), as previously reported in some Japanese)Tj
0.0506 Tw T*
[(patients \(Ohya\). )17.7 (The potential value of SPECT)-282.9 (analysis for)]TJ
0.0078 Tc 0.3671 Tw T*
(the evaluation of cerebral blood flow alterations was)Tj
-0.00011 Tc 0.02499 Tw T*
(discussed \(L. Emmi\).)Tj
0.17751 Tw 1.2 -1.22 Td
(The frequency of ileal and colon abnormalities in BD)Tj
0.1396 Tw -1.2 -1.22 Td
(was found to be 41% in Koreans studied by colonoscopy)Tj
0.2453 Tw 0 -1.22 TD
[(\(Kang\). In another study from a dif)17.7 (ferent center)39.7 (, all 22)]TJ
0.0876 Tw T*
[(patients who had previously under)17.7 (gone intestinal resection)]TJ
0.1053 Tw T*
(had ulcerations at the anastamotic site when visualized by)Tj
0.00549 Tc 0.3694 Tw T*
[(colonoscopy \(Kim\). )17.7 (The need for re-operation in BD)]TJ
0.01331 Tc 0.3616 Tw T*
(patients who required operation was common \(Kim\).)Tj
-0.00011 Tc 0.00391 Tw T*
[(Compared to patients with Crohn\325)54.8 (s disease the ulcers of BD)]TJ
0.11501 Tw T*
(were more likely to be deeper and discrete, round or oval)Tj
0.0428 Tw T*
[(rather than linear)39.7 (, and were focal in distribution rather than)]TJ
0.02499 Tw T*
[(segmental or dif)17.7 (fuse \(Lee\).)]TJ
0.1118 Tw 1.2 -1.2 Td
[(V)110.8 (ascular manifestations are a major cause of morbidity)]TJ
0.12241 Tw -1.2 -1.2 Td
[(and mortality in BD. )17.7 (These complications, often multiple,)]TJ
0.1523 Tw 0 -1.2 TD
[(were reported in 33% of patients from Saudi )54.8 (Arabia \(Al-)]TJ
0.02499 Tw T*
(Dalaan\) and in 14% of patients from Shiraz \(Samangooei\).)Tj
/T1_0 1 Tf
-0.0298 Tw 0 -2.4 TD
[(IMMUNOGENETICS AND )-54.8 (P)73.9 (A)74 (THOGENESIS)]TJ
/T1_1 1 Tf
0.0504 Tw 0 -1.2 TD
(BD is a systemic inflammatory disease, the cause of which)Tj
0.2533 Tw T*
(is still unknown. It is believed that BD is triggered by)Tj
-0.0266 Tw T*
(exogenous environmental factors in individuals with a back-)Tj
0.0063 Tw T*
[(ground genetic susceptibility)64.9 (. S. Ohno reviewed studies that)]TJ
0.15021 Tw T*
(show that BD is closely associated with HLA-B51, espe-)Tj
0.0681 Tw T*
[(cially HLA-B*5101, in a number of populations. )54.8 (Although)]TJ
-0.0358 Tw T*
[(in lower frequency)64.8 (, HLA-B*5108 was also found in German)]TJ
0.007 Tw T*
[(\(8%\) and )17.7 (T)35 (urkish \(19%\) patients with BD, and an increased)]TJ
0.00481 Tw T*
(incidence of HLA-B*51x homozygosity is observed in both)Tj
-0.0164 Tw T*
(populations \(Kotter\). Linkage of HLA-B locus with BD was)Tj
0.25369 Tw T*
[(reported, for the first time, in )17.7 (T)35 (urkish patients, and the)]TJ
0.0685 Tw T*
(contribution of HLA-B to the overall genetic susceptibility)Tj
0.1609 Tw T*
[(to BD was estimated to be 12\32020% \(Gul\). )17.7 (There was no)]TJ
0.08459 Tw T*
(association of HLA-B51 heterozygosity and homozygosity)Tj
0.21671 Tw T*
(with any specific manifestation or a more severe course)Tj
0.0278 Tw T*
[(\(Gul\). )17.7 (The association of MHC class I chain related gene )54.8 (A)]TJ
0.0428 Tw T*
(\(MICA\), first suggested by Ohno, was described in Korean)Tj
0.3653 Tw T*
(patients with MICA6, present in 50% of BD patients)Tj
0.16769 Tw T*
(compared to 26.5% of controls \(relative risk 2.8\), with a)Tj
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0.02499 Tw 8 0 0 8 54.5 35.9844 Tm
[(Schirmer)110.8 (, et al: BD confer)36.8 (ence r)36.8 (eport)]TJ
0 Tc 0 Tw 61.4375 -0.0313 Td
(637)Tj
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(Hippocrates was likely the first to recognize the character-)Tj
0.0471 Tw 0 -1.2 TD
[(istic symptoms of what we know today as Beh\215et\325)54.9 (s disease)]TJ
0.30881 Tw T*
[(\(BD\). )17.7 (This disease is named after Hulusi Beh\215et, who)]TJ
0.0609 Tw T*
(described the symptom complex of recurrent oral aphthous)Tj
0.07829 Tw T*
[(ulcer)39.7 (, genital ulcer)39.7 (, and uveitis as a disease entity in 1937.)]TJ
0.0564 Tw T*
(As more and more patients were diagnosed with BD in the)Tj
0.09641 Tw T*
(following years, an international study group was founded)Tj
0.0473 Tw T*
(to explore the pathogenesis of this disease and to exchange)Tj
0.0873 Tw T*
[(research results and opinions on BD. )54.9 (According to S. Lee,)]TJ
0.0094 Tc 0.36549 Tw T*
[(the term \322Beh\215et\325)54.9 (s disease\323 is used more often than)]TJ
-0.00011 Tc 0.02499 Tw T*
[(\322Beh\215et\325)54.8 (s syndrome\323 in current literature.)]TJ
0.0199 Tc 0.36971 Tw 1.2 -1.2 Td
[(Since 1964, international conferences on Beh\215et\325)55 (s)]TJ
0.0011 Tc 0.37379 Tw -1.2 -1.2 Td
[(disease were held in Rome, Istanbul, )17.6 (T)69.9 (okyo, London,)]TJ
-0.00011 Tc 0.0694 Tw T*
[(Rochester)39.7 (, Paris, )17.7 (T)35 (unis, and last in Reggio Emilia in 1998.)]TJ
0.20979 Tw T*
(At the recent conference in Seoul, Korea, clinicians and)Tj
-0.0186 Tw T*
[(scientists from more than 20 dif)17.8 (ferent countries met again to)]TJ
0.00079 Tw T*
(continue this discussion and exchange on BD. On this occa-)Tj
0.2831 Tw T*
[(sion the International Society for Beh\215et\325)54.8 (s Disease was)]TJ
0.03391 Tw T*
(inaugurated, \322to extend and communicate knowledge about)Tj
0.24879 Tw T*
[(BD.\323 It is anticipated that the study)64.8 (, research activities,)]TJ
0.00751 Tw T*
(education and communication, awareness, and management)Tj
0.02499 Tw T*
(of BD will continue to expand.)Tj
/T1_2 1 Tf
0 Tw 0 -2.4 TD
(EPIDEMIOLOGY)Tj
/T1_1 1 Tf
-0.013 Tw 0 -1.2 TD
[(BD is a universal disorder)39.7 (, with varying prevalence in coun-)]TJ
-0.0016 Tw T*
(tries near the so-called silk route as well as in non-silk route)Tj
0.19701 Tw T*
[(countries \(Zouboulis\). In )17.7 (T)35 (urkey)64.8 (, the prevalence rate has)]TJ
0.0979 Tw T*
(been found to be 80\320370 patients per 100,000 inhabitants.)Tj
0.36211 Tw T*
(The results of a new preliminary study from Istanbul)Tj
0.006 Tc 0.3689 Tw T*
[(revealed a prevalence of 320/100,000 \(Azizlerli\). )17.7 (The)]TJ
-0.00011 Tc 0.1781 Tw T*
(prevalence of the disease is 2\32030 patients/100,000 in the)Tj
0.2706 Tw T*
(Asian continent and 0.1\3207.5/100,000 in Europe and the)Tj
0.0817 Tw T*
(USA. New data from Korea and Iraq suggest a prevalence)Tj
0.2466 Tw T*
(of 18/100,000 \(Roh\) and 17/100,000 \(Sharquie\), respec-)Tj
-0.0323 Tw T*
[(tively)64.8 (. )17.8 (The prevalence rates appear to depend not only on the)]TJ
0.0679 Tw T*
[(patients\325)-244 (ethnic origin but also on the geographic area they)]TJ
0.1953 Tw T*
(are currently living in. In a cohort of US patients, more)Tj
0.0054 Tc 0.36951 Tw T*
(female patients were found than in silk-route cohorts)Tj
-0.00011 Tc -0.0063 Tw T*
(\(Calamia\). Male patients were overrepresented in this group)Tj
0.28191 Tw T*
[(with lar)17.7 (ge vessel disease. Familial occurrence has been)]TJ
0.0407 Tw T*
[(reported in 1\32018% of the patients, primarily in the )17.7 (T)35 (urkish,)]TJ
0.20219 Tw T*
[(Israeli, and the Korean population. )17.7 (T)69.9 (aken together)39.7 (, these)]TJ
-0.0195 Tw T*
(data are consistent with environmental triggering of a genet-)Tj
0.02499 Tw T*
[(ically determined disorder)54.8 (. )]TJ
/T1_2 1 Tf
-0.0298 Tw 26.4 51.5 Td
[(DIAGNOSIS AND )-54.8 (PROGNOSIS)]TJ
/T1_1 1 Tf
0.0159 Tc 0.35899 Tw 0 -1.23 TD
(Diagnostic criteria for BD have been established by)Tj
-0.00011 Tc 0.29761 Tw T*
[(dif)17.7 (ferent centers, and by the International Study Group)]TJ
0.16589 Tw T*
[(\(ISG\). However)39.7 (, especially in the incomplete form, diag-)]TJ
-0.03169 Tw T*
(nosis of BD may still be delayed as much as 2\32015 years after)Tj
-0.0024 Tw T*
(onset of disease. M.A. Chamberlain stressed that such delay)Tj
0.09869 Tw T*
(is of significance, as early treatment, especially to prevent)Tj
-0.0157 Tw T*
[(blindness, is more ef)17.7 (fective. N. Dilsen discussed his own set)]TJ
-0.0265 Tw T*
(of criteria including oral and genital ulcerations, eye lesions,)Tj
0.06531 Tw T*
[(thrombophlebitis, and positive skin pather)17.7 (gy test. )54.9 (Any 3 of)]TJ
0.12759 Tw T*
(these occurring during the disease would be enough for a)Tj
-0.0143 Tw T*
(definite diagnosis of BD. Others confirmed the performance)Tj
-0.0036 Tw T*
[(of the ISG criteria in correctly classifying BD \(T)34.8 (un\215\). In the)]TJ
0.0412 Tw T*
(US and for retrospective studies in which patients were not)Tj
0.2702 Tw T*
[(systematically tested for pather)17.7 (gy)64.8 (, the classification tree)]TJ
0.02499 Tw T*
(may be the most sensitive criteria \(Calamia\).)Tj
-0.0311 Tw 1.2 -1.23 Td
(Oral aphthous ulcers represent the initial manifestation of)Tj
0.00459 Tw -1.2 -1.23 Td
(the disease in the majority of patients worldwide \(47\32086%\),)Tj
0.13989 Tw T*
(whereas at onset of BD genital ulcers are present in only)Tj
-0.03011 Tw T*
(2\32010% of the patients \(Zouboulis\). Genital ulcers may occur)Tj
0.1586 Tw T*
(together with or after the development of oral ulcers and)Tj
0.052 Tw T*
[(usually persist over 10\32030 days. )54.8 (After lar)17.7 (ger genital ulcers,)]TJ
0.02299 Tw T*
(scarring is frequent and is an important finding to support a)Tj
0.02499 Tw T*
(suspicion of BD \(G\232ks\237g\237r\).)Tj
0.07761 Tw 1.2 -1.23 Td
[(A)-272.6 (number of studies confirmed that male sex, early age)]TJ
0.1304 Tw -1.2 -1.23 Td
(of onset of disease in adults, and HLA-B51 positivity are)Tj
0.2948 Tw T*
[(markers for severe prognosis in BD. )54.8 (Additional factors)]TJ
0.1787 Tw T*
(related to prognosis are a delay in diagnosis and lack of)Tj
0.01041 Tc 0.3645 Tw T*
(treatment \(Dilsen, Benamour\). Mortality rates for the)Tj
-0.00011 Tc -0.01289 Tw T*
(disease are between 0 and 6%. In Iran, a country with a high)Tj
0.1492 Tw T*
(prevalence of BD, patients have had milder forms of BD)Tj
0.0966 Tw T*
(since 1993 \(Shahram\). Possible reasons include the earlier)Tj
-0.0117 Tw T*
(diagnosis of the disease or a change in clinical pattern of the)Tj
0.14391 Tw T*
(disease. No such changes were reported for Iraqi patients)Tj
0.008 Tw T*
[(\(Sharquie\). )54.8 (Although rare, amyloidosis in BD carries a 50%)]TJ
0.0887 Tw T*
(mortality over 3\3204 years \(Melikoglu\). Cancers were found)Tj
0.00771 Tw T*
(to be rare in patients with BD in Iran \(Shahram\). Four of 10)Tj
0.0177 Tw T*
(tumors in 4130 cases were seen in patients treated with oral)Tj
0.252 Tw T*
(cyclophosphamide; no cancers were detected after pulse)Tj
0 Tw T*
(cyclophosphamide.)Tj
0.131 Tw 1.2 -1.23 Td
[(Ef)17.7 (forts continue to develop tools for the assessment of)]TJ
0.10921 Tw -1.2 -1.23 Td
(disease activity in BD, and these remain a priority for the)Tj
0.02499 Tw T*
(near future \(Chamberlain\).)Tj
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