symptomatic improvement of gastroduodenal crohn's disease...

BRIEF COMMUNICAT ION

Symptomatic improvement of gastroduodenal Crohn's disease with omeprazole

K W OOLFSON, MD, CR GREENBERC,, MD

K WOOLFSON, GR GREENBERG. Symptomatic improvement of gastroduodenal Crohn's disease with omeprazole. Can J Gastroenterol 1992;6( l ):2 1-24. Four patients with ilea! C rohn's disease presenteJ with abdominal pain aggravaceJ by food, ::i mean weight lo s of 5.5 kg (range 4 co 7) and ulceration of the antrum and/or d~1nJenum at gastroscnpy, without radiological features of mechanical obstruction . The endoscopic and histological appearance of the ulcers was consistent with C rohn's disease. O meprazole 40 mg da ily was admmistereJ, witho ut ocher drugs, and after three Jays of therapy pat ients were asymptomatic. After e ight weeks of omcprazole, a mean weight gain of 6 kg ( range 3 to 10) l 1ad occurred and the Jrug was withdrawn. O ne pat ient remained well and three patients relapsed, but all responJe<l to lo ng term o meprazole for up to three years. Fo llow-up endoscopies have inc.licated healing in one patient, pa rtial healing in two patients anJ no change in one patient. O mcprazolc may be of value in the symptomatic management of patients with gastroduodenal Crohn's disease.

Key Words: Duodenal ulcer , ECL cells, Gasr.,-in, 112-recefnor antagonist

Amelioration symptomatique de la maladie de Crohn gastroduodenale t raitee par l'omeprazole

RESUME: Q uatrc patients acteinrs de maladie Jc Crohn ileale ont rapportc des duulcurs abdominales aggravcc par lcs repas et unc penc pondcrale moyennc de 5,5 kg (4 a 7). L'cxamen g~stroscop ique a rcvcle des ulcerations de l'ancre et du JuoJcnum, sans signe J 'obstruccion mecanique. Les caracterist iques endoscopiquc et histologiques sembla icnt concorder et indiquer une maladie de Crohn. Aprcs crois jours de monothcrapic pa r l'omcprazolc (40 mg/jour) , lcs patients etaicnc asymptomatiques. Aprcs huit semaines, on a constacc un gain ponJcral de 6 kilos (de 3 a 10) cc mis fin au tra itcment. Les rcsultats sc soot maintcnus Jans un cas; trois pa tients one rccidivc mais tous o nt rcagi favorablement a un traitcmem sous omeprazole prolongc jusqu'a tro is ans. Le suivi endoscopique a pcrmis de note r la gucrison chez un patient, un rfaablisscment partiel chez deux patients et aucun changemcm chez le q uatricme. L'omcprazole pourrait s'avcrer uti le dans le cra itemcnt symptomatique des patients porceurs d'une maladic de Crohn gascroduodenalc.

Deparune111 of Medrcin<' ((,rurrnenreroloJ?Y) , Urnwnil'i o/Toronm, Toronw, Onranu Corres/xmdence and re/n·ims: Dr C:; R Ureenberg, l~oom 445, Moum Sinai Hos/ma/,

Toronw, Onwrio MSG IX5. Tele1>hone ( 416) 586-4727 Receiwd far publ1ca1ion Ocwber 3, 1991 . Acct'/ned IJccember I I , 1991

C\N J GA~TRO[NTIROL vu, 6 Nu I )ANL AR Y/rl,BRuARY 1992

CROii N'S DISf:ASf· lvK )ST Cl. )MMONL Y

occurs in the terminal ileum and cnlon , hut 111 I 10 4% of patients thne 1s also 111volve111cnl of the stomach :md duodenum ( 1-3 ). T hese pal ients have po~tprand1al ahdom111.1I pain that often is ~imilar to peptic ulcer dbease, ye t t he maJorit y lose weight, even 111 the ahscnce llf mechanical ohstruction (I). Sympwmatic 1mprov1.'men1 after adm iniscrnt inn of I lz-receptor antagon ists has been reported for p.11 ients with gas1roduudcnal C:rohn\ disease (4), hue fre4ucn1 ly respome, arc 111complete and transient. Recent srud1es mdicate that rnneprazole, a potent mhibitnr of gastric acid secretion, may ht' more efficacious for l he management of patients with duodenal ulcer disease (5) and peptic esophagi tis (6). The present report describes four patients with nonohstruc tive acu ve gast roduudenal Cmhn's disease in whom a trial of omcprazolc therapy ahol ished pain and faci litated weight gain.

CASE PRESENTATIONS Patient I: A 24-year-o ld male diagnosed with Crohn's disease at age 13 years who had undergone re,ect1on of the term ina l ileum at age 20, presen1etl wi th nausea, ep1gastric pain occurring I h postprandially and a 5 kg weight loss over eight weeb. At gastro,copy, there was one ulcer 111 the antrum, one ulcer in the pyloric channel and ,evcrnl aphthoiJ ulcers in the Juodenum. The en-

21

Jo:,copic appcnrnnCL' was cnnsistl'nl

with Crnhn ·~ JisL'ase and hi,1psics shuw

l'd acute and chrnntc.: intla111marinn wirh, 1u1 granulnm.is. Ran it id1m· 300 mg

hid was given an,1 after ti1ur weeb the

pain pani.dly imprnvcd and a weigh t

gain llf 2 kg had \lCClllTL'd. A t gnst1w,

C()i'Y, thl'rL' was ;1 25% hl',iling uf thl'

gastriL ulcers hut the dt11llknal aph-

t hllid ulcL·r:, rema ined ; rnn1t idine

t hnapy w;1s mcreasl'd t, 1 300 mg t id.

H owever, .1fter 12 wecb nl r:tni tidinl'

therapy rhe p,un h.1d pn>,t.:rc,sively w,irsL·ned and there w:1, :1 7 kg weight 1,,ss.

At end11:,c11py, th L' pylnric channe l

ulcL·r was larger and n new I cm ulcer in the ,lu,ldenal cap was prL'sL'nt; aphthuiJ

ulcers in the , lullden urn remained.

Ri\lpsie, shuwed acute and c hrnniL in

fl ,1 m m,11 ion w1t h,iut g r ;111 11I Pm,1s.

0111eprn:olc 40 mg rn1Le dail y was ,wn eJ ;mJ after 72 h therapy t hL' p ,1l il'nr

w.1s ;1:,ym11rum;1t ic. After t WP IVl'L'ks llf

,1mepramle ;1 2 kg weight g;1in had uc

curreJ, hut end,1scopy showed persist

ent ulcerntiun in the anirum ,mJ the

duodenum. Omcpn1Zl 1lc "'"" cunt inueJ for a further six \VeL•ks and then

withdr· wn. Within 72 h , n,lllSL'a ,rnJ

ahdrnnina l pain n.·curred which .1g,1 in

rcsp,mded to 0111epra:llle. A I t 1:r 12

w1:eks o l um1:pra:olc :1 weight gain of I 0

kg occurred hut L' nduscop ic findi ngs

WL're unchanged. As fu rther ,ll tempts w withdraw umeprnwle c.1usL'd recur

rence ,if pain, this 111cdic.1tiun has hL'L'n

c,1ntinuL'd long tL'rm. Aft1:r three years,

l hL' patient has rL:maincd m,ymptllmat ic

with ;1 !()tell 1wight gain 11t 18 kg tha t

ha, st,1 hi I i:1:d, nl though g:1st ruscupy

sh owed persbtcnt hut nunprngres,ivc

ulceratilm in the ,mtrum and du11-

dcnum. Basal scrum ga,trin levels were

96 pnwl/L (11,n·m ,d fasting valu1:, le"

1h:m lO) a nd gastric h i,1psil's have n\lt

sh,1wn crnen1c hn1111affi n Lel l - lik e

(ECL) hyperplas1:1.

Patient 2: A 22-y1:ar-,1ld 111:1k presented with q1igastric pain unrelated tu

food. A n upper ga,tniin te,tin:11 hanum

rnd iograph id1:nt il°ieJ a dumkn.d ulcer; thncfnre, the fo111ily practit1(1nu ad-

111 ini~tered ranit 1d1ne 150 mg hid .

Failure of ranit1dine tll alleviate pain

C1lltplcd with a 5 kg weight loss

prompted rderral. Uastrmcopy ,h,iwed

22

mult iple aph1 hl>id ulcers in the first and

,ecPml p,lrtillib of the dundcnum and

marked duml1:nitis cun,istL'nt w ith

Crohn 'sdisease. Rilip,iL's revealed acutL'

and chronic 1nflammat ion without

granulomas. A ,uh,equent ,mall howcl

L'l1L'ma identifiL·d nonobstructive

C rohn\ , li,easL' involving thl.! terminal 15 cm (ll ileum; ClilonllM:npy was nor

mal. Ranit11.linc wa, increased to 300

111g 11d ,md 5-aminos,ilicylic acid (Pen

ta'-1; NordiL L1hunitmies) 750 mg t id

wa, ,tarted. A ft er ,ix 11·eL·ks of therapy

th1: ahdom in,d rain was unchangL'd.

Rani tidinL' w,1s ,topped, umepraznk 40

mg lllKl' d:1ily w,1, started and aflL'r 72 h the pat icnt was ;isymptom,ll ic. After

four weL·ks of 11111L'prn:ole a I kg WL'tght

g,1in had l1ccu 1-rL·d, hut endusc11pic find

ing, were unchanged. umcpra:ole was

cont inuL'd tur a furl hL'r tour wecb and,

,is the patil'nt r1:111aincd asy111ptrn11;11 ic

and weight had incrc;1,ed a further 3 kg,

the drug was withdrnwn. After four day,

the ahd,Hn 1nal pain l"L'Curred hut rc,

punLkd ag,1in t11 omcpr.i:ok. As with

drawal of umepra:1 ,k 1m threL' , uhsc

quent occ1sil11b cause,I recurrence of pain , the 111cdicati11n has hL·cn cunrinu

ed lnr 18 m1n1ths. The patient remains

asymptomatic with a wrnl weight gain

1it' 7 kg that has ,tabili:L'd, a lthough at

L'n<.Jo,c,ipy multiple aphthrnd ulcl'rs rL'

mained in rhc dundL'num. Basal scrum

gastrin kvels werc 71 pmol/L and

gastric h1op,ies h.1vc nnt sh own ECL

cd l hyp1:q1lasia.

Patient 3: An 18-yL'ar-(ild m,1k· dL:vd

Ppcd Crohn 's ilcit i, a t age 16 years and

w.1s rre.111:d w ith sulphas:da:im· and

prednis\1m·. Suhs1:quently, cimctidinc

was presc rihL'd f,ir duudL'n,d ulcL:ration

idl'ntifiL'd at ga,u·n,copy. The patient

rL'm,uncd well for t1nc ycm on no mcJ1-

cation then presented with L'pigastric

p;un 11ccurring I h poscprnndially and

weight loss of 3 kg over two nmnths.

Casrmscnpy revealed t hrec prcpyloric

ulcers, lll1L' ulccr in thl' duodenal cap

and llnl' ulcL·r in the pnsl bulbar

duudl'num; the pylorus was patent hut

lacked pliabil ity. T h e endoscopic ap

pearancl' wa, cnn,istent with Croh n's

dise,1sl' and hillpsie, , howed acute and

d1ronic inflammation hut no granu lo

mas. Uppl'rgastro111test1nal radiographs

, h o wed no gastric ou tl et 11r duodenal

llhstructinn. Ranitidine 300 mg bid pn ,

vidL'd only partia l rL'licf of pnin and wa, incrL'ased to 300 111g cid. After 16 weeks

of treatment a further I kg wl.!ight loss

occu1-rL·d and the ulceration w," unch,mged at ga,t roscopy. Rnni1 idine wa,

dbcontinul.!d and oml'prn:uiL' 40 mg

lH1Cl.! daily was started; ahL'r 72 h of thL'rnpy ahdomin,il p,1in was ;1hsenr.

A ftL'r two weeks ot t1mepr:1zoli.: w1:1ght

gain o( I kg had occurred .111d m gastn1-

scopy the pr1:py loric ulcL:r, were

reduced in size by 50% ;111d aphthoid u lcers with mild dundeniti, rem:uned.

After four WL'1.:b nf omeprn:11lc a furth e r

2 kg weight gain had occurred :md at

ga,trnscopy the stomach was nt1rmal

hut p1:rsistent aphthoid ulcc r:, with , luu

den irb remninL'LL After eight weL'ks llf omepra:nlc the pa t ient rcm.1ined

asymptomatic, had a (urt her 2 k1-: weight

gain and at endoscopy t1nly mi ld duu

denitis was present. Omcpraznlc was

disconl inued and the p ,11 ient has

remained wdl w ith srnble 1VL:ighc on n\l

mcdic<1tion a fter three ye;ir, of hillow

up.

Patient 4: A 31 -year-olJ k mak w,i:,

diagnosed with Crohn's ikou,litis and

severe p1:ri an a l dbcasL' at agL' 29 year,

and, after one year of medical th1:rapy,

unde rwent a total colcctomy. S h e h ad rL:maincd wel l without medication fnr

one year and Lhcn presented with l'Jll·

gastric pain occurring I h aftL'r meals,

retrosternal burning nnd a 6 kg weight

lms over 14 weeks. A t gastrn,c,1py,

there WL'l"L' thrL'c ulcers urcumferL'ntial

ly arranged around the prepylnric

antrum and a pyloric c hanne l ukTr; th e

duodenum w;is normal. BiupsiL·, ,huw

L'd acutL' and chronic intbmmatiun

wichou tgranuloma~. Ran it idinc 150 mg

hid was started, hut after t w1i WL'eb ,if therapy th L'rC was no improvement and

the J os1: was increascd tu 300 mg rid.

After e ight wcl.!b u( rnnllidine thL'rapy ahd1Jminnl pain 1Tmained, b i li11u:,

vomi ting dl'vclnped :ind cn,11>,cupic

find ings wc 1T unchnngcd. Biopsic,

showL'd aculL' and chronic intlamm.i

rion and grnnulom,ts were idL'ntifiL'J.

Omcprazulc 40 mg once dail y was ,rnn

ed and aftL'r three Jays of tre,1t111ent

ahdo111 inal p,iin wa:, a l1,enr. Aft1:r four

weeb ol 0111qsrn:nle, a 11•ci1 .. d1t gain of 1 kg had occurred ,md gasl mscopy shl 1wed thar the prepylll ri c ulcn s had reduced hy 50%, hut three new ,1phtho id ulcers were identified m,1re prox imnll y in the antrum, and apht ho id ulce rs wi rh dunden i ti s we re now prese nt in th e Jumlcnum. O meprazole was c,mt inued for a furrher lour wceb , and weight inc reased hy 6 kg. As the p;1t ient W,ls asymptnmar ic the drug was wit hdrawn. However, three weeb hte r the pal ien t returned with nausea, epigastric pa in and a Z kg weig ht l,iss I hat aga in responded 1,1 omeprn:ole. S ince suhsequent withdra wal ll( nmeprnzole caused recurrence n( pain, th is medic ui,1n w.1s given long te rm. A r 22 nwnths of treatment the p:1 t ient became pregnant ; omeprazlllc was cont inued and the pregnancy w,1s une ,'l'ntfu l with the de li l'e ry o f a hc,ilthy fe ma le . The pat 1en l rcma i ns asymptn ma t ic afte r three years ,m omeprnwlc wi th stahle weight, bas,il serum gastrin levels pf 72 pmo l/L; h \lwe ,·er, a t endos<.:opy the prepyloric and dun,lcna l ulce rnt H1n \\'as unc ha nged. Cias tri c hiops ies have shown n,> EC L cell hype rplasia.

DISCUSSION T he four patients descrihed with ac

tive C rnhn 's disease of the gastrodundcnum and res is tant to thernpy with an Hz-receptor antagonist sho wed sympromat ic improvement and p,1rr i.d en doscopic regression aft er trea t mcnr with rnneprazole. Consistl'nt with ,1ther repo rts (I , 3,7,8), Crohn's clisc,1se involving the sto mach and/or dunck num was nor always easily differen tiated from convcntillna l peptic ulcer.i t ion. T he p1-csc'nr pat ienrs expe rienced similm symptoms of ahd,1minal p,1in, alrhough a ct>ntrasting fea ture w,1s marked weigh t loss no t wirhsrnndinl! the ;i hsence n( ml'c han irn l fnregut nhstruc t ion.

Moretwer, in acc,1 rd with prel' ious findings, h isto logy was frl'qucntly no t conclusive O) as hinpsy spec imens showed grnnulomas in only one of rhc present patients. The end(1scopic appearance of a1,hrhuid lesi(111s and thei r presence hcy(>nd the dundcm1I c,tp, coupled with ident ilka t icin of Crohn 's disease elsewhere in the gut, have heen

suggested as the lllllst import.mt signs fur the di ,1gnns is ,if gastroduodenal C rohn\ di ,case. In uther series (4,7) , Cn)hn's d isease occurred in rhe d1sral smal I howd and/or coh in in 8 3 w 9 3')(, p ( pat ienls 11rcsenting with involvement o( the .~astmdt1t >dcnum. A ll f,1ur o( the present pat ients had Cmhn's disease e lsewhere in thl' intest inc, hu t in ,inc p,1rient ilcit is was found on ly afte r the emlnsc1 >pie ,lppcarance sugges ted the d iag1wsi, o f C roh n's disease.

Numc1\ 1us approaches have hcen advoca ted for rhe treatment of pat ients with gastroduodenal Crohn's disease. An ti -ulcer regimen with l-1 2- receptor ant ;1gon ists and antacids were reported to provide sympto mmic re lief in five of l O 11,1tients for two to n ine months, hut then curt icos teroids were requi red ( 4). O ther moch1lities includ ing cort icostcroid,, singularly or in combinat ion with tn ta l paren tera l n utrit ion hal'e heen successful in the t remment of indiv idual pa tients wtlh gastmduodena l C rohn 's d isl'asc (9- 1 J ). 1-lmvel'er, in a rel'iew ot SC\'era l series hy Priebe and S imon (7) 23 of 30 patien ts ultimately came 1,1 surgery. T hus, any t hcrnpy th,11 dimin1.', hes sympt oms, f,1c il1tntcs weigh r gain and precludes the need (,1r cort ico,terrnds or surgery would be ,1d -1·antageous.

O mcprn:o le, a ,elect ive 1-l \K+. A TPase inhihitm is the most potent suppre,srnu uf gast ric acid sccretllln currently ,wa ilahlc for use in humans ( 12). T his drug provides rapid sy mp111-m,1 tic relief for pat iL'nts with con vent in n a l d undcn,d u lcn d bease ( 5) and has hec..:nme the agenr of ch(1 ice fnr nrn nagement of patients with crosil'e peptic esophagiri , (6) and the Zll llinger-Ell ison synd romL' ( 13). These findings coupled with ohservat illns that pharmacul,1gica l suppression uf acid ,ccreti ,in might achil'l'e sympw mat ic relict in patients wi th ga,rmduodenal Cmhn's d isease (4) provided the impel us for a rria l of omcprn:ole therapy Ill the present pa tients. Sympwmatic impn>\'l'mcn t with we ight gain was rapid and sustained in all four pa ricnts, hut import antly, none were mechani ca lly o hsrruc tcd . T he mechanisms tha t accounted for the marked reduc t ion of pa in , wh ich in turn fa..:i li ta tcd food in -

CAN J GA~TR( WNTrn, )[ Vt ll 6 Nn I j ANlJARY/Fl-loRL I •\RY 1992

Omeprazole a nd Crohn's disease

i,:cst1<>n ,111d ll'l' 1ghr g;i in , arc llllt ent1rely clear. Hllll'l'\'l'r, the speuficity of omeprn:,ile for hincling Ill the panl't,d L:c'II pmton pump ( 12) docs implic ll L' , ,1t least 111 11,trt, ;1 role fur ga,tric ac id.

ln three llt t hl' 11,H icnts there was nnly p,1rtia l nr nn ulcer heal mg at end,1-scopy, hllWL' l'Cr, nonl' ha, shown pn>gre,s ion uf gastroduodenal d isease. To 111,tinta lll wcll-heing in tlwse patien ts, treatment wnh ,imq,ni:nle ha, hccn requ ired for up to three years. Cllncerns have hccn rn ised regmd ing the long te rm use of omcpra:,ilc in h umans hecausc, in nits, ECL cel l hyperpl asia and the subsequent dcve lnpmetH ot gast ric carcinoids has been reported ( 14 ). T he causat ive mechanism fo r these nh,en·atinns b nnw knuwn to he a trnph1c response to the susrn incd hypcrgasl nnemia that , in turn , 1s rclared to the marked acid suppression hy omeprawlc ( 15). I lowever, in humans, rnneprn:nlc adm inb tcred for up to 24 mon th~ ha~ not hcen associmed with e ither ECL cell hyperplasia , or the developmen t of g,1st ric carc ino1ds ( 16). Similarly, in rhc present p,11 ,ents, t here was no hiswlogical L'v 1drnce f11r ECL cel l hyper-1~las ia. Scrum gastrin levels have rema11wd elevated hy two- to th reefold tiver v,1 lues nhscrl'ed in hcalt hy suhjects, hut notably the same magnttude nf ra ised scrum ga,trin concentrations occurs in patients rec..:e ivmg 112- receptnr an tagonists long te rm, and without unt,1wmd effects . Alth,1ugh limited, the present L'Xpcriencl' wirh long term admm i~tra t ion of omeprawlc indicate~ an ah,encc nf side effects, hut (unher cva luat inn wtth larger series o( patients 1s clearly requ i1Td.

In summmy, l~iur patient s with nlln ohstruct il'C ga,trodundcnal Croh n's d i,case showed symptom,1tic improvement wi th omeprnzolc. A thempeuric t rt al of omcprazole 1m1y he of value in s1milm pat ients prior to instituting cnrt icosteroids or perform ing surgery.

REFERENCES I. Fd dmg JF, Toye DKM, Rcto11 DC.

Cooke WT. Cl'(lhn', di,l'a:,c of the sromach and duodenum. Gut 1970;1 1:1001 -6.

2. F,mncr RC, I lawk WA, Turnhull RR Jr. Cn,hn\ d,,c.isc "{ the duodenum ( l rarn.mur,11 duodcn it b); (. I 111 ,ca l

WOOi FSl)N '\NI) GRFENT\ERl,

manifestation,. Repon, of l l case,. Am J Dig Dis l 972; 17: 191 -8.

3. Nugent F\XI, RichnmnJ M, Park SK. Crohn ', disease of I he duodenum . Gur 1977; 18: 115-20.

4. Murrny JJ, Schnet: DJ, Nugern FW, Coller JA, Vcidenheirner MC. Surgica l rn,ingcmcnt of Crohn\ disease invnlving the du"dcn11111. Am J Surg 1984; 147:58-65.

'i. u1uritscn K, Rune SJ, Rytzer P, Cl al. Effect nfomcprazolc and cime1 idinc in duodena l ulcer. N Engl J Med 1985;3 12:958-6 1.

6. Sandmark S, Carlss<>n R, Faus;1 r, ct al. Omcpraznlc or rnniridine in the t rea1 mcnt of reflux esophagi! is. Result, of ,1 douhlc-hltnd randorn1zcd Scandinavian multit:cntcr study. Scand J G;1woen1erol I 988;21:625- n.

7. Priebe WM, Simnn JR. Crnhn's disease nf the SI nmach with, ,ut oh,1 ntCt inn:

24

A ca,c rcpon and review of rhcrnpy. J CltnC:i;1,trocn1crnl I98l;5:44l -5.

8.

9.

IO.

ll.

12.

Abu Rhama AF. Gastroduodenal l 3. Mm<m PN, Vigayck R, Frucht N, ct al. Crohn 's disease. South Med J Lon~-term efficacy f!ml s;ifcty of 1979; 72:551-4. ompramlc in patients with Fil:gibhons TJ, Green G, Silbermc1n 11, Znlli ngcr-EII ison syndmme: Elia,ophJ, HalbJM, Ycllin AE. A prospective swJy. Gastroenternlogy Management nf Crohn's disease l 989;97 :827-36. involvi ng the duodenum, including 14. Ekman L, I lansson E, H::ivu N, du"dcnal cutaneous fistuh1. Arch Smg Ca rlsson E, Lundhcrg C. Toxicological 1980; 11 5: l 022-8. stud 1c~ 0 11 omcprazole. Sc,md J Vogel CM, Carwin TR, Banc AE. Gastrocntcrnl I 985;20(Suppl Intravenous hypernltmentation in l 08):51-69. the treatment of infl;1mmatmy disc<1scs 15. L,m,son 11, Carh.son E, Mausson l l, uf the howe l. Arch Surg ct al. Pl;isnrn ga,1 rin and gas1 nc 1973; 108:460-7. cntcrnchromaffin-lih: cel l act iv:irion Nugent FW, Roy MA. Duodenal and proli(cr;i1 ion. S1 udie., wnh Crohn's disease: An analysi, nf89 omeprazole and ranitidinc in intact cases. Am J G:1s1 rocnternl and antrecrorn izcd nus. I 989;84:249-54. Gasrrocntcrology l 986;90: 39 1-9. Wallmark I\ Rrandst mm A, Larrson 16. Lambcrts R, C rcutzfcld W, Stockmann H. Evidence for ,ic,d-mduccd F, Jacubaschke U, Maas S, Rrunncr (~. rrnmforma1 10n of nmcprnznlc mw an Long-term t,mcprnzolc treat men I in ac t ivc inhihiror llf H

1 ,K

1 -ATPa,c 111,111 : Effects on g;-1srric endocnnc

within the parietal cel l. Rinchcm cell popu lacions. Digest inn Riophys Acta 1985;8 I 7:25- lZ. l 988; 19: 126- 35.

CAN J CiASTROENTEROI VOi 6 No I JANUAR.Y/Frnt,UARY 1992

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

symptomatic improvement of gastroduodenal crohn's disease...

Documents