ISSN 00 11 -9059 GODEN IJDEBB
`
`..,...___ ________ ~ Dermatology
`
`Volume 36, Number 12
`
`Univ. ·ot ·Minn.
`Bio-Medical
`Library
`
`

`
`ISSN 0011-9059 GODEN IJDEBB
`
`-Dermatology
`
`Volume 36, Number 12
`
`Univ. ·ot ·Minn.
`Bio-Medical .
`Library
`
`Exh. 1010
`
`

`
`942
`
`Clinical trial Rosacea
`
`Torresam. Pavesi. and Manara
`
`2.
`
`thcrapcutic potential in su pc rficia l a nd systcmic mycoscs .
`Dmgs 1 990; 39: 877- 9 r 6.
`l'aergc ma nn JF, La ufen 1-1. Levels of flu conazolc in sc rum ,
`stratum corncum , epidcrmis-dcrmis (w ithour srratum
`corn curn ) and cccrin c swcat. Ctin t x t;cr Dcrmatotr99 3;
`18 : 102- 106 .
`N:rd:r M, Sa id A. Efficacy and safcty of sin glc-dosc oral
`flu co na zok in rhc trcarrnent of fun ga l sk in infccrions.
`.frmmat o( l'an-Ara/; Lcague o( Dermalotogisls 199 1; 2:
`l h5- 173 ·
`4 De i Aguila R , Montcro-Gci F, Roblcs M, el at. O ncc-
`wcck ly om l closcs of flucona zo le 150 mg in thc trcatmcnt
`of tinea pcdis. Clin f.xpcr Der111atol 1991.; 17: 402-406 .
`Montcro-Cci Fand Percra A. Thcrapy w irh fluconazole
`fo r ti nca corporis, tinea cruris and tinca pcclis. Ctin !n(cc/
`Dis 19 92; 14 (Suppl. r ): 577-58 1.
`6 hrra g A, Said A, T:1h:r M, Wacl ic N. O ra l fluconawlc in rhe
`trea rmcnr of rinca cruris . .foumat o( Pan-Ara/; L.eague u(
`Dennalotogists 1992; 3= 107- 11 5.
`
`7 Abclci-Aal MA, Korb M, Said A . Fluconazole: a new drug
`fo r rrcarmc nt of derm :n omycoscs. Egypt.f Oer111atol
`\lenereo/1 993; IJ: II)- 11 7 .
`8 Ahd-A il a h M A, EI-Sa yed MI-I, Ra shid A, Sa id A. Oral
`singlc dosc of fluconazo lc in rhe rrearmcnr o f rinca
`corporis ancl rinca c ruris. Lgyp!.f V cmwlot Venereu t
`1 994; 14: 8 s - 89.
`9 Abou-Zcid S, EI-Ma nsy I. Fluconazo lc, s ing k week ly dose,
`in rhc trea tment of tinca corporis a nd c ruris . .foumal of
`Pan -Ara/; Ccague o/ Der/1/a/o/ogists 1994; s: I 21-124.
`1 o Such il 1', Monre ro-Gei F, R ob lcs M, etal. O ncc-wcck ly
`o ra l do sc\ o f fluconazolc 1 50 mg in thc trc:nmenr of tinea
`co rpori s/cruris and cura ncous ca ndi d iasis. Cl in Exper
`Dermatot r 99 2; I7= 397-40
`1 r Rck:r ccw icz I, Cu ill a u mc J C, Ben k hra ba F, el at. Do ub le
`b lind placc bo contro lled stud y of a 2 per ccnt foa ming
`Iotio n of kctoconazolc in a sing le app lic:Hion in thc
`trcatm cn t o f pityrias is vc rsico lo r. Ann Dermatot Venereut
`1990; I 17= 709- 7 I I.
`
`Clinical trial
`Clarithromycin versus doxycycline in the treatment of
`rosacea
`Claudio Torresani, MD, Angelo Pavesi, PhD, and Gian Carlo Manara, MD
`
`Forty patients with rosacea were entered into a study comparing clarithromycin with
`doxycycline in the systemic treatment of mild and severe rosacea. The patients, 25
`women and 15 men, aged from 26 to 62 years, were subdivided into two homogeneous
`groups with regard to age, sex, and disease severity. The first group of 23 patients, 14
`women and 9 men, was treated with 250 mg of clarithromycin for 4 weeks twice daily, and
`then with 250 mg once daily for the following 4 weeks. The second group of 17 patients,
`11 women and 6 men was treated with 100 mg of doxycycline for 4 weeks twice daily,
`and then with 100 mg once a day for the following 4 weeks. Both objective and subjective
`evaluations of the dermatosis were performed prior to therapy and alter 4, 6, and 8 weeks
`of treatment.
`
`From the Departments of
`Dermatology and Evolutionary
`Biology, Parma University, Parma,
`and Private Dermatologicat Practice,
`lmola , ltaly
`
`Correspondence
`Claudio Torresani , MD
`Department of Dermatology
`University of Parma
`via Gramsci. 14
`1-431000 Parma
`ltaly
`
`Drug names
`clarithromycin: Biaxin
`doxycycline: Vibramycin
`
`lntorna(lonal Journal ol Derma/otogy 1997. 36. 938-946
`
`© 1997 Blackwel l Sc1ence Ud
`
`Exh. 1010
`
`

`
`Rosacea Clinical trial
`
`943
`
`D Group 1
`[I Group 2
`
`Torresani, Pavesi. and Manara
`
`Objective evaluations
`Frythe1na
`starus was asscssed hy a co lorimcrri c
`Th e ery rh em::1
`rec hniqu e pcrfonned o n color prinrs o f th e parienrs.'
`This sysrem (M in o lra C:ro m a rnercr m ode l CR 300, üsa ka,
`.Japa n ) e11ablcs
`rhe mca surcm cnr o f
`rhe sk in co lo r.
`Var ia tions of eryr hcma a re
`reprcsc ntcd by a
`si11g lc
`nurn cri ca l va lu e.'
`
`Telangiectases, papules, and pustules
`Th c 11umhers and dim cnsio ns of re la11giecrascs (TAE)
`wc re cva lua tccl from the co lor prinrs a 11d a scorc W<lS
`::1ssigncd o n rh e basis of rh c followin g sc::1lc: o, 110 TAE;
`r, lcss rhan five TAE loc::1tcd
`in rhc na so la hi a l sulcu s
`a ncl
`in
`the regio zygom arica ; 2., 5- 10 TAE locarcd in
`rhe naso l::1bi a l sulcu s a ncl
`111
`rhe regio zygo m atica; -''
`bcrween 10 a ncl 2.0 co nflu enrs TAE; 4, 2.0-30 TAE, a lso
`d iffuscd ro rh e chin a n d foreh ea cl; 5, m o re rhan 30 TAE.
`Th e numbcrs of pap ulcs a ncl pusrul es wcre eva lu ared
`from rhe co lo r prinrs a nd a sco re was assigned o n rhe
`ahs is of thc following sca le: o, no lcs ions; 1, less than
`5 lcs ions; 2., 5-1 o
`lesio n s; 3, 1 o-2.0 lcs io n s; 4, 2.0-30
`lcsio11s; 5, morc rhan 30 les ions.
`
`6
`
`-
`
`6
`
`4 -
`
`3
`
`2
`
`0
`
`Subjective evaluations
`
`subj cctive
`ro exp ress a
`requ es red
`Each parienr was
`ev,llu:ni on abo ur rhe cfficacy a 11d
`rol erahiliry of rhe
`rrcarm cnr by assig11ing a score bascd o n a sca le ra 11ging
`frorn o ro 5. Lf(icacy: o, 110 cfficacy; 1, low c ffi cacy; 2.,
`rra ceah le cffi cacy; ), mild e ffi cacy; 4, goocl cffi cacy; 5,
`high efficacy. T!J/era!Jility: o, 11 0 sicl e-effecrs; 1, occasio nal
`sy m pto1ns; 2., m '1n y sympto m s; 3, mild sid c-effecrs; 4,
`scve re sid e-cffccrs; ), very ser io us sidc-effccrs (indu cing
`paricnrs to clisconrinuc rh e rhcrapy) .
`
`Statistical methods
`
`Starisrical cvaluarion of rh c dara coll cctcd from clarirhro-
`rn yc in -<l nd dox ycycl ine-trea red pa rierns was pc rfor mccl
`b y univa ria re a nd mulri va ria rc srari srical analy scs.
`Th e mcan va lu cs of rhc eryrh em a ind ex in rhc rwo
`g roups of paricnrs we re comparcd by a Srudcnr's /-resr,
`afrer 4 wceks (T r ), 6 wce ks (T2.), a ncl X wccks (T3)
`o f rh erapy.
`No npa rarn erric resrin g o f rhc diffcrcnces bcrween rh e
`mea n values of rh e or hcr va riabl es umler ex aminarion
`(TAE, papu lcs, pusrules, effi cacy, and rol er,lbiliry) was
`ca rri ccl our by ,l Mann-W hirn ey U-rcsr.
`The homogcnciry of rh e rwo groups o f par icnrs was
`a ssessccl by co m par iso n, prior ro rrcarmenr, of rh c rnc,ln
`
`Tl
`
`T3
`
`Figure 1 Eryrh cma. Mecm va lues of 6E in clarirhromyci n-and
`clo xycyc linc-rrearcd gro ups of paricms afrcr 4, 6, ,1nd 8
`wceks. Ar tirnc T 3, afrer X wccks of rre,nmcm , no signi ficanr
`diffcrcnce was obsc rvcd . Asrcri sks dcnore rhc Ievel of
`srari srica l significa ncc: ,,. P< o .o5; ,,. ''. l' < o .oo5; ,,. ,,. ". P< o.ooo 5
`
`(no
`
`"TAE va lu es and papulc a nd pusrul c va ri ables
`signifi ca nr differencc was cxpecrcd ar T o).
`in add it io n , a mulriv,Hiare sr,nisrica l arwlysis w,ls per-
`form ccl. Accordi ng ro rhc di scrimin ,nn funcrion m crhod , a
`ncw variabl e was ulculared for eac h pa ricnr, as a lin ea r
`comhinari o n o f rh e va lues ohra in ccl for cryrhcma, TAF.,
`pap ul es, aml pusrulcs. Th c rn ca n va lu es of rhi s new variabl e
`in rh c rwo gro ups of paricnrs werc sr,ni sri c,lil y co mparcd
`ar T 1, T2., a ml T1 by 'ln cli ys is of va ri a nce .
`
`Results
`
`Ar th e end of rh e rrecnm cnr, rhe ovc ra ll restrlrs providccl
`ev id cnce for a hi gher cla rithrorn ycin cffi cacy p ro fil e in
`compar ison w irh doxycyc lin c. Th c o urcome assessm enr,
`bascd o n rhc different pararnercrs co nsidcrcd, n:vca led rh e
`fo ll ow in g dara.
`
`Objective evaluations
`
`Lrythenw (1-'ig. 1)
`(P < o.oo;;)
`significanr differcnce
`rhe
`Fi gure 1
`shows
`herwec n rhe m cc\11 val ucs of rh c eryrhcrn'1 ind cx in rh e rwo
`
`© 1997 Blackwell Science Llcl
`
`lniemanonal Journal ol Oermaloiogy 1997. 36. 938- 9,16
`
`Exh. 1010
`
`

`
`944
`
`Clin ical trial Rosacea
`
`Torresani. Pavest. and Manara
`
`D Group 1
`[I Group 2
`
`4
`
`2
`
`1
`
`0
`
`D Grou p 1
`[I Group 2
`
`4
`
`3
`
`2
`
`-
`
`1
`
`0
`
`T0
`
`Tl
`
`T2
`
`T3
`
`T0
`
`Tl
`
`T2
`
`T3
`
`Figure 2 Telangiccra scs (TA E). Mean va lucs of TAE scorc in
`rhc rwo groups of p,Hients ar To (bd orc starring rrearmenr),
`T1 (4 wceks o f rrcarrnenr ), T2 (6 wccks o f rrca rmcnr), and
`T 3 (H wce ks of rrca rmcnr ). Asrcrisks represenr rhe Ievei o f
`srarisrica l significancc: ••· P< o.os ; ··· ·•·f' < o.oos ; ,,. ,, .. ,.P< o .ooo s.
`rhc horn ogcnciry o f rh e rw o groups is incl ica rccl by rh c Iac k
`o f srari srical signillcancc ar time To
`
`Figure 3 Papu lcs. Mcan va lu cs of p~ pulc scorc in rhc rwo
`p;ni em gro ups hcforc srarring rrcarm cnr (To } ~nd afrer 4
`wceks (T 1 }, 6 wee ks (T2}, and R wccks (T3) of rrcarmcm.
`Thc ho mogc11ciry o f rh e gro ups is indic n cd by rhe Iack of
`sra risrical significa!lcc ar time To. Asrcrisks rep rcsent rhc
`Ievei o f srarisrical signillca nce: ,,. P< o .o 5; ,. ,,. P< o .oos ;
`·•· ,,. ,,. P< o .ooo 5
`
`gro ups of pa ri cm s ohscr vcd afrer both 4 and 6 w ee ks of
`trea rment ( mean ::':: srand a rd erro r). At time T 3, a ftcr 8 wcc ks
`of treatm enr, no signifi ca nr differcnce was demun strated.
`
`Telangiectases (1--"ig. 2)
`A significant diffcrcncc (P< o .os) berwec n rhe rn can va lues
`of th e spec ific scorc eva luaring th c nurnhcrs a nd dirncn sions
`of TA E in th c two groups o f pari cnts w as ohserved aftcr
`4 wecks o f trca rmcnr. N o signifi canr differcnces wc rc
`demo nstra tccl ,lt T 2 and T J .
`
`Papules (l'i~. 3)
`A sign i fi ca nt ly fas tcr clec rcasc (l' < o.ooo 5} of rh e mea n
`sco re eva luarin g rhc nurnht: r of pa pu lcs was asscssed in rh e
`c la ri rhro myc i n-rrca red pa ri enrs, w hen com pa red w i rh th c
`d o xycyc lin c-rrca rcd p::tticnts, afrer 4 and 6 wcc ks o f thcra py.
`No sig11 ifica nr diffcrcnccs wc re fo un d ar T j .
`
`Pustules (1--"ig. 4)
`Th c rcs ulrs o hra in ccl fro 111 a sra ri srica l co mpa riso 11 bctwee n
`rh c rn ca n va lu cs of rh c sco re eva lua ring rhc numher o f
`
`pusru lcs we re fo und ro bc srri ctly similar to rhose rcporred
`rh e nurnber o f papulcs. A s ignificanr diffcrence
`fo r
`(P < o .ooos) bcrwcen the e ffccrs of rh c rw o rcg imens was
`a ssessccl ar rimes T1 :mcl T2. . A cornparison of rh e m ean
`va lues o hsc rved ar rh e end of rherapy did not revea l a Ieve l
`o f sratistica l signific:m ce.
`
`Subjective evaluations
`
`J:fficacy (hg. s)
`No stati sri ca ll y significant cliffcrences we re o bse rved in th e
`two groups o f paticnrs ar T1 , T2, and T3 .
`
`T(Jierability (Fig. 6)
`Th e tora l rn ca 11 ro lera hi liry m casured in G ro up 1 parierns
`at rh c clarithro m yc in trcatm em rate used was equa l to 0 .3 2.
`(occasio na l siclc-c ffet:ts) . Th e rora l m ean ro lerabi liry sco re
`mcasured i11 G roup 2. pari enrs at th e doxycycline trca rm enr
`rare uscd was cqua l to 1 .o 6 (mi ld sicl e-effects}. A compa r-
`ison of t he rn can valucs of th e c Hicacy and rol era bil ity
`
`lniema{Jonal Joumal of Dermatoiogy 1997. 36. 938 9'16
`
`© 1997 Blackwell Science Ltd
`
`Exh. 1010
`
`

`
`Rosacea Clinical trial
`
`945
`
`D Group 1
`[I Group 2
`
`<***)
`
`Torresam. Paves1. and lvlanara
`
`(* ** )
`
`[] Group 1 m Group 2
`
`(* **)
`
`5
`
`4
`
`3
`
`4
`
`3
`
`2
`
`1
`
`0
`
`-
`
`T0
`
`Tl
`
`T2
`
`T3
`
`0
`
`Figure 4 l'usrul es. Mcan valucs of pusrulc score in the rwo
`paricnr groups before rrearmcnr (To), ;l!ld <1frer 4 wceks
`(T r ), 6 wccks (T2.), ancl 8 wcc ks (T ;) of r rc~nm e n r . Tbc
`homogcneiry of rhe groups is inclicarcd by rhc Iack of
`srarisrical significa ncc :lt To. Asrcrisks dcnorc rh c Ievei of
`srarisrical signi ficance: ••· P< o.o 5; "· ·•· P< o.oos; ... "· ·•· P< o.oos
`
`T3
`
`Figure 5 Efficacy. Mcan valucs of rrc;Hmenr efficacy scorc.
`Thc score was assigncd by borh thc paricnrs of rhe
`clarirhrorn ycin-rrca rccl group and th c cloxycyclinc-rrcarccl
`group. i\srcrisks dcnorc rhc Ievei of sr:Hisrica l sign ific:1nce:
`'' l'<o .o s; ·•· ·•· P< o.oo<; ; ··· ,,. ••· P< o.ooo <;
`
`indices showcd highl y significanr di ffcrences hcrwecn th c
`rwo groups of paricrlts (hgs 5 and 6) .
`
`Discussion
`
`Discriminant function method
`The final srcp of srarisric:1l :1nalys is included th c use of
`linear discrirninant ana lys rs as a rnulti vari:Hc approach. A
`compar ison o f rh e mcan valucs of rhi s ncw variable was
`rhen pcrformed by analys is of va riance. A highl y significanr
`differcnce was clemonsrr;ned ar T1
`:1nd T2. (f-' = 44. 18,
`P< o .ooos) . This furth er emphasizes rhc rcsulrs prov idcd
`by uni variare arul ys is. Mo re inrercsrin gly, :1 significanr
`clifferencc (I-- = 5. ), P< o .oo s ) was :1lso dcmonsrrarcd ar
`time T 3, rhus ~ll ~)po rrin g :1 highcr cffic:1cy protilc of ci:lr-
`irhrom yc in vc rsus do xycyclinc :H thc end of thcr:1py. ln
`adcl irion, rhe fa srcr im pruvemenr deriving frmn cbrirhro-
`rn yc in trc:ltment w:1s demonsrr:lted by rh c fa ct rh:lt no
`srarisrical cliffercnce (F= o.8 1, P< o .o s ) was ohscrvcd in a
`cornpa riso n hctween rh c effc cts of do xycyclinc rrc:lt111Cilt
`a t T :; wirh rhose of clarirh romycin ar T2.. T his analys is
`indic:Hcs thar (, wccks of clar irhrom yc i11 rrearmcnr arc
`equ iva lcnr ro 8 wccks o f cloxycy linc rrc:Hmcnr.
`
`Thc eriology ancl parhogc ncs is of rosacea a rc srillunknown .
`The sysremic dru gs tirsr used m rhe rreannenr of rosacea
`were tetracyclincs.'·' T his was fo llowed by rh c introdu crinn
`of metroni cb zole.·1 Both
`rh crapies achieve signific:nlt
`im provcmenrs of dermarosis in So% to 90°/., of cases;l·>
`and no sratisricall y signitica nt diffcrcnccs wcrc observed
`hcrwcen thcm. '
`The ph:nmacologic mcch:1n isms of acrion of both
`metro nidazole :1 ncl rerracyclines h:1vc bcen widcly in vesri -
`g;:ncd. Thc th cra peutic acri vity of rerra cychncs seems ro bc
`rci:Hed ro rh eir anri-inflammatory efticacy.6
`Clarirhromyc in , a rcccnrly synthesizcd rnacrolide, has
`in to ph:1gocyrcs
`becn proven ro bc :1blc ro pcncrrarc
`i11 l'ilro J T hc prcsem srud y revcals rhar clarirhrom ycin is
`a powcrful rool in
`thc trearmenr of rosace:1.
`Ir yiclds
`improve menrs w hich a re signiticamly more consisrcnt w hen
`compan:d wirh rhose ohra inecl wirh cloxycyclinc. ln co nrrasr
`wirh tcrracyclines and merronidazolc, cl:!rirhrmn yc in is a
`ve ry sa k therapy inclucing on ly occasio nal and slighr siele-
`
`© 1997 ßlackwell Sc 1ence Lid
`
`lntema/Jonal Journal of Oermatology 1997. 36. 938- 946
`
`Exh. 1010
`
`

`
`946
`
`Clinical trial Rosacea
`
`Torresam. Paves1. and Manara
`
`D Group 1
`~ Group 2
`
`correlarion herwccn clin ical imp rovcmcm a nd a haremcnr o f
`rhe 1-/clico!Jacter pylori isolares and sc ro lo gy afte r tre<Hmcnr
`wir h merron idazole.'1 ßccause clarirhro mycin is cffecrive
`aga insr 1-lelicobacf('}" pylori, rhis co ul d ex plain rhe effic 1cy
`of rhis macrolide in rh e rrcarmenr of ros<lcea. ' 0
`hirther srudi es wi ll yield ncw insighrs inro rhe pha rmacol-
`ogic mcchani sms of <lction of cla rirhrom yc in in rhe rrear-
`rnenr of rosacca.
`
`1.2
`
`(*)
`
`1
`
`0. s
`
`0. 6
`
`0.4
`
`0.2
`
`0
`
`References
`1 Scirz .JC, Whi rmorc C:G . Mcasurcmenr of crythcrna and
`ranning rcsponscs in human skin using a rri-srimulus
`colorimercr. Dcrlllatologica 1988 ; 177: 70-7 5 ·
`2. Sncdclon lß. i\ clinica l trial of retracyclinc in rosacca. Br
`j /) ennatol 1 966; 78 : 649-6 F·
`3 Knight AG, Vickcrs CFI-1. A follow- up of terra cyclinc-
`rrcarcd ros::1cca. ßr ./ Demwtol 197 5; 93' 577-580.
`4 Pyc RJ, Burton .J L. Treatment of rosacc<l by
`mctroni dazo lc. La11cef 1 976; 5: 1 2. 1 1- 1 2. 1 2..
`Sa ihan EM, Burton JL. i\ double- blind rr ial of
`metroll idazolc vcrsus oxytcrracycl inc thcra Jl)' for
`rosacca . Br .J /)crmatol 1 98o; ro2: +U- 445·
`6 JVLu·rin RR, Warr G/\, Couch RB, cl <1/. Effcct of
`retr;lcyclinc on leukorax is . .J l11/cct Dis 1 974; 129:
`I T0- 1 16.
`7 An d c r~on R, .Joonc C , Van Rensburg LJ. An i11 uitro
`cvaluation of thc ccll ular uptakc :1nd in rrap hagocy tic
`bioacrivity of chrithrom yc in (A-562.6S, T I:::-03 1 ), a JH:w
`macrolidc anti microbi,d agcnr. .J Alltimicro!J Cliemoi/;cr
`19XS; 22: 92>-91>·
`8 Re horn A, D1:agl; f., Parodi A . !Vb y /-lelim/;actn pliylori
`he irnpo rra nt fo r dcrmatoJogistS) f)I!I'Ji/CitO fog)' I 99 5;
`I 9 1: {,-S .
`9 Rcbo r;l A, Dr;1go F, Picciotto A. !-leficol;acfer /! )'Iori in
`pati cnrs with rosacca. Am .J Castmellleml 1 994; 89:
`1603- 1604, (Ietter).
`1 o Torrcsan i C, Baroni E, Mana ra CC. l.a claritromicina
`nc l rrarramcnro dclla rosacca . A/;sfr,ICI:> o/ the 6ytli
`Natio11al Co11gress o/ the ltalian Suciety o/ Den natulogy
`and Vcncreolugy . .June J- .f , 1 'J'J.f. Sorrento, ltaly, p. 45 7·
`
`Tl
`
`T 2
`
`T3
`
`i r y sco re o f thc
`Figure 6 Tolerab il iry. Mean va lucs of ro l er;~ b i l
`two rcgirnens. Thc score was sub jccrivcly ass igncd by rhc
`rwo groups of parients. Astcrisks denotc thc Ievel of
`sratisrica l significancc: ''. P< o.o5 ; ,,.,,.P<o.oos; ,,. ,,. ,' P< o.ooo 5
`
`effccrs. T his significanrly incrcascs parienr comp li ancc and
`is of partin dar inrcrcsr w hcn considerin g rhc long-re rm
`rherapy rcq uired . T he mechanism of ::~ cr io n of rhc clr ug in
`clermarosis has nor yer hccn csrabl ishcd. Ir is concciv-
`rh ar clarirhromyc in a lso h::1s
`anri-i nfbmmarory
`able
`capa bi liries.
`Rebora et a fB reccnrly fou nd J-lelico!Jactcr pylmi in rhe
`gasrr ic juices of 84 'Yr, of 3 1 paricnrs suffcring fro m rosacca .
`They suggcsrcd an eriologic relat ionshi p berwcen rosacca
`an d 1-lelicobacter pyluri in fccrions o n rhe basis of rh c
`
`International Journal of Oermatofogy 1997 , 36. Cl38- 916
`
`© 1997 ßlackwell Sc1ence Lid
`
`Exh. 1010