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1 '( #$! %&!" (ADA)!"#! #),% - ' ( ) * - % -!"# "/ 2 1 -,. / %01%,% 45 + ' () *#!" "#!$ %& : AB..@ 9: ;< =# &>?!* 5 6.!" 7"8,# /../,-& (Cut off Point) H BE GA "# 8 > "#!$ %& +(ADA) >?G>?!F"8 *E D. 2C../ 6L "#!$ K 3 (CSF) 'I J >?G>? ("# 8!$ 21 "#!$ 21)!$ K 42 +""O -M AB G : 5 3 > Z >.../ ( 1386 V# 3.> (4) 7B G " (U) KT9 +" 3# *!& # +^>" 6 - F >!& 6L # +G\] +.< +V"# #![5 'I J ## 'I J >?G>? _B#..a V# +>?G>? _B# `L# '..a # 7# H BE GA ROC O ^d# c./ *E ba!$ K 21 ( %19) 3> 4 ( %81) 17,/ +"#!$ K 21 4L : h 'I J >?G>? G..@a < AB ( %34) 3> 7 ( %66) 14,/ "#8..?!# 10/5U/L "#!$ %& 7# H BE.(P<0/0001) j ba G A i. %85/71 %80/95 7 _B# G!M)9!#*C %& +10/5U/L H BE > b# "#!$ 3 + 'I J >?G>? _B# :../.. 3*m" 3*# 3# "#!$ "# 8!$ c"#!$ c 'I J c>?g>? : :(2) )* '+, -!./0! /4/25 :GH, 1387/4/15 :C DEF 1387/11/16 :@ 3.> -/'] 6" b& +-/'] b.-& +#/7#? />? ba # 2 3.> -/'] 6" b& +(4) 7B G " 3# jeeo A# ' + Z/'] cvn* b.* 1 q] - 3 p@ m B) > :=? b_narouie@yahoo.com :--!*] : :G" 3 3.> -/'] 6" b& +-/'] b.-& +() -"9 />? ba & 4 3.> -/'] 6" b& +-/'] b.-& + />? ba & 5 3.> -/'] 6" b& +(4) 7B G " 3# jeeo A# ' + Z/'] 6 3.> -/'] 6" b& +-/'] b.-& +"9 />? ba # c %) r@ 1 54

2 1388 % J I2.+ I16. )* '+, -!./0! 1!# I x VC c(6-4)!#. K) >?G>?!# b 3& AB Z 4.O H> "#!$ %&..] `'@ '!$ b$!$ >?G>? _B# +3- Rohani AB.(2) 3>? Z + 'I J < +. "#!$![5 )& < &>? > &![5 )& ;< J# & Z 3 +a u# AB.(7)./. "#!$ 6L 8U/L H BE GA 3- Gambhir!# %75 %44 7!M)9!#*C +./ BE 3& +3- Choish ;EO.(8).? %&. %9/ Z 3 15U/L H.(9)./ "#!$ * +"#!$ q-& ** +/ 6L 'I J!#@.# '?p - ma c/!kz L + %20 ue@ %& j< &.. `'@ 3? 3' `>? J ^>" 6 -!& 3.m ita.@ c! v 'I z.c 7* 'I J > >.E 3> %80 'I J!&. > L >"] bl> ` +VC G c!# < b# %& ' (PCR)!# G- +(MRI CT) ) # 75C b (~5 AKh8..& #..(12-10) / b..] O 3*# +./ >a ([ Z,# L? > `'@ >?G>?.E F % 6. jm ' K) b#! s 75!# G- +J< 3 %& G > c./ &a, < 8 t!$.!/ F!. & K) (... = + ) >, 5[ A,# 6@ GJ/ "#!$../ 'I b] 6 -,# u#./ K) *# v ita "#!$.(1) a L ^>" ^>" 6 - [! 3./VA@ +3> ` +# +7,/ &.. 7../ x& ya2 + +3a # +w# -'@ GJ/ $ ZO.(2).? /!" "#!$ %&,z ' () *# x.(2)./,-& + #!$!# > "C v:!o "#!$!" 7"8,# /./ >8? 3 ;< =# &>?!* 5 6. h &>?!* &..@ 9: "#!$ => %&![5 +./ 6L VA * '? (ADA) >?G>?.(3+1)./ =*C.. ' G>? > G? >#.5!#!# z- '? G "M Z '@ -" "# & Z 3 3?!A@!# uk + 5 V"# * }#] +.A =#...] `'@ (CSF) 'I J >?G>? _B# G jt9 > 3? r@ "#!$ %& Cut off Point ** Acid Fast Stain Polymerase Chain Reaction * Adenosine Deaminase Deamination Cerebrospinal Fluid 55

3 '( #$! %&!" (ADA) } -#] p#,9 > ^] "M@ b&>?../ V# b&>? j. +# 5 20 # b# >?G>? _B#.A >.[ 7/ Z '? /!/ u# b./ 9# >?G>?! > ab>. RA 1000 '? b# (3!9#) "C ab>. / `../ 6L G>? > G? >#.5 V "C./ 6L j"a '? 6 "C / >? q? b./ +U9 Z#? b.va@ jl * >. Vh (~5 `! # 7G. / ' B (NADP + NADPH,.K) 340 Ä.!/.9 >?G>? '? (!F"8)!A@ E* ba >?G>? G 3?!# >.A >?G>? H BE +ROC O # +y" GA "#!$ K 3 'I J "#!$ ba 3 AB G..a K#O!M)9!#*C.../. *E "#8 +A DO +G 3![5 M? > b./ +>?G>? E J> 3 V G D GA![5 3>? > "# 8 "#!$ ba G >?G>?../ b# : #!$ K 42 +V# Z 1h 21 (%50) "#!$ 21.@a < (%26/2) #!$ 11,/ +"# 8!$ K 21.. (%23/8)!$ 10 %19) 3> 4 ( %81) 17,/ +"#!$ * Glutamate Dehydrogenase Enzyme Allosteric Activator Enzymes Receiver Operator Characteristics,# +7# H BE GA 3 3?.E > >?G>? ab>..(14+13) %& J# b#,# 3 )& H #.(16+15)./ J# 3> * +/ 3*# 3#,# T 4/ "#!$ J# 3! +3*m" %&! +J# ;< &>?!* G b. D../,L* "#!$ => 'I J >?G>? *E # +AB GA "# 8 "#!$ K 3 ba 'I J >?G>? )& H BE.!# b "#!$ K (ABE 4 >) ""O -M AB G 21 "#!$ 21)!$ K +" 3# * ("# 8!$ 1386 V# 3.> (4) 7B G " (U) KT9.../ ( =# H _B# `'@ +!$ %& &>? K J!Kz!& # +"# H/ +G\] >./ b# VA h!# b 'I J ## 5 +!$ 3 +G\] +.< 3' +V"#.A #![5 'I ^>" 6 - F >!& # >?G>? _B# `L# +!& # > Z ^d# c.a V# b&>?./ G# +^5 +a9 6 6,/ h 6@ 3 J # x G c.a,- + %& 6 -!& # + 'I > ^] 'I J >?G>? _B# ^>"../ b'@ 6@ +[ 56

4 1388 % J I2.+ I16. )* '+, -!./0! 1. 9/39±5/18 "#!$ ba >?G>? G *E > & "# ba 3' G 3& "# 8 A i ba D9 G!# "#8 ROC O 5 +AB G.(P<0/0001) %&![5 7# H BE +(1 ) b./# G@a F.!# b./ K#O 10/5U/L "#!$. G T "#!$ ba %81 +.E G "#8!$ ba.. G G] %19. G G] %85/5. G T %14/5 %85/71 %80/95 7!M)9!#*C....?!# 14,/ "# 8!$ K 21 ( # b.o.. ( %34) 3> 7 ( %66) G V# "#!$ ba G V# #!$ +45/10±19/61 G V# 62 15!$ 36/18±12/21. 34/30±13/89 K 3 'I J '? Å x 7 ( +#) "# 8 "#!$ J >?G>? G.!# b./ b 3& 1 V.5 +23/04±13/10 "#!$ ba (U/L) 'I!$ +9/66±7/21 #!$ ba +( #) "# 8 ba Ç, 9/10±1/28 8/ *./', - '() * + ' $%& -1 * ±1003/40 (3200-7) /30±9/34 (100-70) 90 9/70±9/34 (30-0) /83±1033 (9000-0) /60±62/55 (260-15) 91 26/90±19/19 (65-6) 25 9/10±1/28 (12-8) 9 * /30±38 (160-6) 10 7/44±3/64 (25-0) 5 96/36±7/44 (100-75) /06±32/27 (160-0) 10 50/82±22/185 (80-17) 45 71/27±48/69 (211-35) 60 9/66±7/21 (30-5) 7 * /97±314/81 (1400-0) /86±10/85 (40-0) 10 74/86±32/82 (100-0) /26±2792/71 ( ) /80±161/81 ( ) 80 38/67±22/41 (98-5) 34 23/04±13/10 (56-6) 22 (mm 3 ),.# VK"a (mm 3 ) \" D "] (mm 3 ) (mm 3 ) (mm 3 )!# '< VK"a G\] (mm 3 ) '"a (U/L) >?G>?..b./ z.c -,<.C +A DO G jm E! 57

5 '( #$! %&!" (ADA) Kashyap AB 19!$ 41 +"#!$ 117) V9./ ba 104 #!$ >?G>? G +(./ 8 Z "#8 +"#!$ ba (U/L) 'I J 9/25±2/14 +14/31±3/87 7 V!$ >?G>? H BE. 2/71±1/96 +.E G G@a F.?!# 11/39U/L "#.(2) %83 %82 7!M)9!#*C!$ Prasad AB Zd#?!$ 12 +!$ 15 +"# J >?G>? G +./ 6L./ ba "#!$ ba (U/L) 'I 0/64 +0/9 +1/89 +6/43 7 V Zd#?!$ %&!* G!M)9!#*C % /30U/L > & H BE "#.(4)./ H'a % 97/8 BE G@aF ' 3- Rohani AB "#8!$ %87/6!M)9 +9U/L H ;EO G >,MC x &.C.?!# J >?G>? 3' 3& AB G../ 3>? Z 'I < +. "#!$![5 )& )& 3>? & # )& ;< J# & Z 3 +a < u# AB.(7)./. "#!$![5 BE G@a F +./ 6L 3- Gambhir %75 %44 7!M)9!#*C +8U/L H [m 3- Choi AB.(8).?!#!$ 130 +"#!' 36) AB ba!$ 7!$ 9 +# 'I J >?G>? G +(Vd $/> 0?9 3 = ;< 3 ROC * -1 0:7 *./', - )0;:0) 9 3 *9 12 ;8# ba >?G>? _B# u# AB G ("B H BE G 23/04U/L "#!$.?!# 10/5U/L "#!$ %&![5 G] & # b./6l jab 7"8!K*../ "#!$ ba >?G>? G *E > & "# ba 3' G 3& "#8. A i ba D9 G!# "#8 > "C v:!o "#!$ x 7"8,# /./ >8? 3!# ;< =# &>?!* 5 6.!" G b 3&.A jab.(3+1).@ 9: %& 'I J >?G>? 3'!#. K) jt9 > 3? r@ "#!$ AB Z!# I x VC c(6-4) "#!$ %& >?G>?!# b 3&!$ b$!$ 4.O H>.(7). `'@ ' 58

6 1388 % J I2.+ I16. )* '+, -!./0! 1 >?G>? / [&] AB G x 5 Z GA / * j a y" J5 "#!$ %& 6>T +.C H EB!# 6>T. J5.a jm F G AB 49 %9 b.-& b& &$] 6O!A > -& b&>? 3-3.> -/'] 6" b& -/'] A# ' L& jeeo +3.>.C 3.> -/'] 6" b& jeeo.. AB G 6L!$ +#!$ +"#!$ ba [m (U/L) +12/76±7/53 7 Vd!$ c./ H'a 7/24±4/38 7/38±3/27 +2/58±2/37 15U/L H BE 3& AB G G b.z "#!' %& %9/ Z 3.(9)./ =< J >?G>? G +AB G "#8 "#!$ ba (U/L) 'I _2 D9 9/39±5/18 23/04±13/10 7 ("B H BE.(P<0/0001)!/ 5 A..?!# 10/5U/L "#!$ %&![5 :>#' 1- Eintracht S, Silber E, Sonnenberg P, Koornhof HJ, Saffer D. Analysis of adenosine deaminase isoenzyme-2 (ADA(2)) in cerebrospinal fluid in the diagnosis of tuberculosis meningitis. J Neurol Neurosurg Psychiatry. 2000; 69 (1): Kashyap RS, Kainthla RP, Mudaliar AV, Purohit HJ, Taori GM, Daginawala HF. Cerebrospinal fluid adenosine deaminase activity: a complimentary tool in the early diagnosis of tuberculous meningitis. Cerebrospinal Fluid Res. 2006; 3: SütlaE PN, Unal A, Forta H, Senol S, KirbaE D. Tuberculous meningitis in adults: review of 61 cases. Infection. 2003; 31(6): Prasad R, Kumar A, Khanna BK, Mukerji PK, Agarwal SK, Kumar A, et al. Adenosine deaminase activity in cerebro-spinal fluid for diagnosis of tuberculous meningitis. Ind J Tub. 1991; 38 (9): Baro M, Acevedo L, Lagos M.E. Usefulness of adenosine deaminase determination in cerebrospinal fluid for diagnosis of meningeal tuberculous: 4 years experience at a public hospital. J Rev Med Chil. 1996; 124 (3): Pettersson T, Klockars M, Weber TH, Somer H. Diagnostic value of cerebrospinal fluid adenosine deaminase determination. Scand J Infect Dis. 1991; 23 (1): Rohani MY, Cheong YM, Rani JM. The use of adenosine deaminase activity as a biochemical marker for the diagnosis of tuberculous meningitis. Malays J Pathol. 1995; 17 (2): Gambhir IS, Mehta M, Singh DS, Khanna HD. Evaluation of CSF-adenosine deaminase activity in tubercular meningitis. J Assoc Physicians India. 1999; 47 (2): Choi SH, Kim YS, Bae IG, Churg JW, Lee MS, Kang JM, et al. The possible role of cerebrospinal fluid Adenosine deaminase activity in diagnosis of tuberculous meningitis in adults. Clin Neurol Neurosurg. 2002; 104 (1): Azizi F, Hatami H. Epidemiology and Control of Common Diseases in Iran. 2 nd ed. Tehran: Teimoorzadeh Publication; [Persian] 11- Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, Jameson JL, et al. Harrison's Principles of Internal Medicine: Infectious Diseases. Translated by: Mohaghegh Montazeri S, Farhoodi B. 1 st ed. Tehran. Teimoorzadeh Publication: [Persian] 59

7 '( #$! %&!" (ADA) 12- Simon RP, Aminoff MJ, Greenberg DA. Clinical Neurology. Translated by: Bigvand Shahrooz F. 1 st ed. Tehran: Nasle Farda Publication: [Persian] 13- Yagawa K, Okamura J. Role of adenosine deaminase in activation of macrophages. Infect Immun. 1981; 32 (1): Andreasyan NA, Hairapetian HL, Sargisova YG, Mardanyan SS, Badalyan LT, Khanoyan AS. Activity of adenosine deaminase and its isoforms in pleural fluid in tuberculous pleuritis. Med Sci Monit. 2002; 8 (10): CR Andreasyan NA, Hairapetyan HL, Sargisova YG, Mardanyan SS. ADA2 isoform of adenosine deaminase from pleural fluid. FEBS Lett. 2005; 579 (3): Valdés L, San José E, Alvarez D, Valle JM. Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy. Eur Respir J. 1996; 9 (4):

8 1388 % J I2.+ I16. )* '+, -!./0! 1 Abstract Original Article Comparison of cerebrospinal fluid adenosine deaminase concentration of tuberculous and non-tuberculous meningitis A.A. Niazi 1, B. Narouie 2, A. Moghtaderi 3, R. Alavi Naeini 4, S. Yaghobi 5, A.S. Sheikhzadeh 5, M. Shahriar 6 Background and Aim: Diagnosis of tuberculous meningitis is difficult because of its non-specific clinical presentations which may be confused with other disorders of central nervous system. The initiation of anti- TB medication can often be delayed because of lack of available laboratory tests. This study was aimed at evaluating the adenosine deaminase (ADA) concentration in differentiating tuberculous meningitis from nontuberculous meningitis to determine the cut-off point of ADA in the cerebrospinal fluid (CSF) of tuberculous meningitis patients. Materials and Methods: In this descriptive-analytical study, 42 meningitic patients (21 patients with tuberculous meningitis and 21 with non-tuberculous meningitis) admitted to Boali, Khatam al anbia and Ali ebne Abitaleb hospitals in Zahedan between 2006 and 2007 were selected. From each patient 5 ml of CSF was taken and sent to laboratory to analyze ADA concentration, cells, blood sugar, protein, smear and culturing of Mycobacterium tuberculosis. ADA concentration of CSF in TB meningitic patients was compared with that of non-tb meningitis patients. By using receiver operator characteristics curve (ROC), the optimal Cut-off point for tuberculous meningitis was determined. Results: Out of 21 patients with TB meningitis, 17 (81%) were males and 4 (19%) females; and out of 21 patients with non-tb meningitis 14 (66%) were males and 7 (34%) were females. There was a statistically significant difference (P<0.0001) between mean of ADA levels in CSF among the TB and non-tb meningitic patients. The cut off value for the diagnosing of TB meningitis was 10.5 U/L with a sensitivity of 80.95% and specificity of 85.71%. Conclusion: This study demonstrated that ADA concentration in the CSF of TB meningitis patients, using a cut off value 10.5 U/L, can be useful in diagnosing of TB meningitis in Sistan and Balochestan province. Key Words: Cerebrospinal fluid (CSF); Adenosine deaminase (ADA); Tuberculous meningitis; Non tuberculous meningitis Journal of Birjand University of Medical Sciences. 2009; 16 (2): Received: Last Revised: Accepted: Assistant Professor, Department of Pathology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan Iran. 2 Corresponding Author; General Physician, Zahedan University of Medical Sciences, Clinical Research Development Center, Zahedan Iran. 3 Associate Professor, Department of Neurology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan Iran. 4 Associate Professor, Department of Infectious Diseases, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan Iran. 5 General Physician, Zahedan University of Medical Sciences, Clinical Research Development Center, Zahedan Iran 6 Assistant Professor, Department of Internal Medicine, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan Iran