10(Helicobacter Pylori an Introduction)

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Volume: I: Issue-3: Nov-Dec -2010 ISSN 0976-4550

HELICOBACTER PYLORI: AN INTRODUCTION

Arshad Mehmood5, M. Akram1, haha!"#dd$%1, A&'a( Ahmed), *ha% Usma%+ha%$,

A!d#( Ha%%a%

, E. Moh$#dd$%

-

, M. As$&

5

,Department of Basic Medical Sciences1, Department of Medicine and Allied Sciences2,Department of Preclinical Sciences3, Department of Surgery and Allied Sciences2

Department of Pre-clinical Sciences4, Faculty of astern Medicine, !amdard "ni#ersity$

Department of %on#entional Medicine&, 'slamia "ni#ersity Ba(a)alpur

INTRODUCTION

Since t(e introduction of !elico*acter pylori to t(e medical community *y Mars(all and+arren almost t)o decades ago, !elico*acter pylori (as *een t(e focus of *asic

*ioc(emical and clinical researc( and de*ate$ 'ts rele#ance to (uman disease, specifically

to peptic ulcer disease, gastritis, and gastric malignancy, is indisputa*le$ Many uestions,

(o)e#er, still remain concerning t(e optimal diagnostic and t(erapeutic regimens )it()(ic( to approac( t(e organism

!elico*acter pylori is a gram negati#e, microaerop(ilic*acteriumt(at can in(a*it #arious

areas of t(e stomac(, particularly t(e antrum$ 't causes a c(ronic lo)-le#el inflammationof t(e stomac( lining and is strongly lined to t(e de#elopment of duodenal and gastric

ulcers and stomac( cancer$ .#er /0 of indi#iduals infected )it( t(e *acteria are

asymptomatic$ (e *acterium )as initially named %ampylo*acter pyloridis, t(enrenamed %$ pylori pylori geniti#eof pylorus5 to correct a 6atin grammarerror$ +(en

17S r89Agene seuencingand ot(er researc( s(o)ed in 1:/: t(at t(e *acterium did not

*elong in t(e genus %ampylo*acter,it )as placed in its o)n genus, !elico*acter$ (egenus deri#ed from t(eancient ;ree


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!.ram et al ISSN 0976-4550

0$+#re 1: He($o!aer 2/(or$

!elico*acter pylori possess fi#e maKorouter mem*rane protein .MP5 families$ (e largest

family includes no)n and putati#e ad(esions$ (e ot(er four families include porins, irontransporters,flagellum-associated proteins and proteins of unno)n function$ 6ie ot(er typical

;ram-negati#e *acteria, t(e outer mem*rane of !elico*acter pylori consists ofp(osp(olipidsand

lipopolysacc(aride 6PS5$ (e . antigen of 6PS may *e fucosylated and mimic 6e)is *lood

group antigens found on t(e gastric epit(elium$ (e outer mem*rane also contains c(olesterolglucosides, )(ic( are found in fe) ot(er *acteria$ !elico*acter pylori (as 4-7 lop(otric(ous

flagellaI all gastric and entero(epatic !elico*acter species are (ig(ly motile due to flagella$ (e

c(aracteristic s(eat(ed flagellar filaments of !elico*acter are composed of t)o copolymeriJed

flagellins, FlaA and FlaB2G

3e%ome

!elico*acter pylori consist of a large di#ersity of strains, and t(egenomesof t(ree (a#e *een

completely seuenced$ (e genome of t(e strain


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H$sor/!elico*acter pylori )as first disco#ered in t(e stomac(s of patients )it( gastritis and stomac(

ulcers in 1:/2 *y Dr$ Barry Mars(all and Dr$ 8o*in +arrenof Pert(, +estern Australia$ At t(e

time t(e con#entional t(ining )as t(at no *acterium could li#e in t(e (uman stomac( as t(e

stomac( produced eHtensi#e amounts of acid of strengt( to t(e acid found in a car *attery$Mars(all and +arren re)rote t(e teHt*oos )it( reference to )(at causes gastritis and gastric

ulcers$ 'n recognition of t(eir disco#ery, t(ey )ere a)arded t(e 200&9o*el PriJe in P(ysiology

or Medicine$;erman scientists found spiral-s(aped*acteriain t(e lining of t(e (uman stomac(

in 1/L&, *ut t(ey )ere una*le to cultureit and t(e results )ere e#entually forgotten$ (e 'talian

researc(er ;iulio BiJJoJerodescri*ed similarly s(aped *acteria li#ing in t(e acidic en#ironment

of t(e stomac( of dogs in 1/:3$ Professor+alery Na)orsiof t(e Nagiellonian "ni#ersity in

Ora) in#estigated sediments of gastric )as(ings o*tained from (umans in 1/::$ Among some

rod-lie *acteria, (e also found *acteria )it( a c(aracteristic spiral s(ape, )(ic( (e called i*riorugula$ !e )as t(e first to suggest a possi*le role of t(is organism in t(e pat(ogenesis of gastric

diseases$ (is )or )as included in t(e !and*oo of ;astric Diseases, *ut it (ad little impact as

it )as )ritten in Polis($ Se#eral small studies conducted in t(e early 1:00s demonstrated t(e

presence of cur#ed rods in t(e stomac( of many patients )it( peptic ulcers and stomac( cancer$!o)e#er interest in t(e *acteria )aned )(en an American study pu*lis(ed in 1:&4 failed to

o*ser#e t(e *acteria in 11/0 stomac( *iopsies $

'nterest in understanding t(e role of *acteria in stomac( diseases )as reindled in t(e 1:L0s )it(

t(e #isualiJation of *acteria in t(e stomac( of gastric ulcer patients$ (e *acterium (ad also *een

o*ser#ed in 1:L: *y Australian pat(ologist 8o*in +arren,)(o did furt(er researc( on it )it(

Australian p(ysician Barry Mars(all*eginning in 1:/1$ After numerous unsuccessful attempts at

culturing t(e *acteria from t(e stomac(, t(ey finally succeeded in #isualiJing colonies in 1:/2

)(en t(ey unintentionally left t(eirPetri dis(esincu*ating for & days o#er t(e aster )eeend$ 'n

t(eir original paper, +arren and Mars(all contended t(at most stomac( ulcers and gastritis )ere

caused *y infection *y t(is *acterium and not *y stressor spicy foodas (ad *een assumed *efore

24, 2&G$ Alt(oug( t(ere )as some septicism initially, )it(in se#eral years numerous researc(

groups #erified t(e association of !elico*acter pylori )it( gastritis and to a lesser eHtent ulcer$o demonstrate t(at !elico*acter pylori caused gastritis and )as not merely a *ystander,

Mars(all dran a *eaer of !elico*acter pylori culture$ !e *ecame ill )it( nausea and #omitingse#eral days later$ An endoscopyten days after inoculation re#ealed signs of gastritis and t(e

presence of !elico*acter pylori$ (ese results suggested t(at !elico*acter pylori )as t(e

causati#e agent of gastritis$ Mars(all and +arren )ent on to demonstrate t(at anti*iotics are

effecti#e in t(e treatment of many cases of gastritis$ 'n 1:/L t(e Sydney gastroenterologist

(omas Borody in#ented t(e first triple t(erapy for t(e treatment of duodenal ulcers$ 'n 1::4, t(e

9ational 'nstitutes of !ealt("SA5 pu*lis(ed an opinion stating t(at most recurrent duodenal and

gastric ulcers )ere caused *y !elico*acter pylori and recommended t(at anti*iotics*e included

in t(e treatment regimen4G

8ecent researc( states t(at genetic di#ersity in !elico*acter pylori decreases )it( geograp(ic

distance fromast Africa, t(e *irt(place of modern (umans$ "sing t(e genetic di#ersity data, t(eresearc(ers (a#e created simulations t(at indicate t(e *acterium seems to (a#e spread from ast

Africa around &/,000 years ago$ (eir results indicate modern (umans )ere already infected *y

!elico*acter pylori *efore t(eir migrations out of Africa, remaining associated )it( (uman (osts

since t(at time

International Journal o !""lie# $iolo%& an# '(armaceutical )ec(nolo%& 'a%e:1339

!vaila*le online at+++,ia*"t,com
http://en.wikipedia.org/wiki/Barry_Marshallhttp://en.wikipedia.org/wiki/Robin_Warrenhttp://en.wikipedia.org/wiki/Perth,_Western_Australiahttp://en.wikipedia.org/wiki/Car_batteryhttp://en.wikipedia.org/wiki/Nobel_Prize_in_Physiology_or_Medicinehttp://en.wikipedia.org/wiki/Nobel_Prize_in_Physiology_or_Medicinehttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Stomachhttp://en.wikipedia.org/wiki/Microbiological_culturehttp://en.wikipedia.org/wiki/Giulio_Bizzozerohttp://en.wikipedia.org/wiki/Walery_Jaworskihttp://en.wikipedia.org/wiki/Jagiellonian_Universityhttp://en.wikipedia.org/wiki/Krak%C3%B3whttp://en.wikipedia.org/wiki/Gastrichttp://en.wikipedia.org/wiki/Robin_Warrenhttp://en.wikipedia.org/wiki/Barry_Marshallhttp://en.wikipedia.org/wiki/Petri_disheshttp://en.wikipedia.org/wiki/Easterhttp://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/wiki/Spicehttp://en.wikipedia.org/wiki/Endoscopyhttp://en.wikipedia.org/wiki/Gastroenterologyhttp://en.wikipedia.org/wiki/Thomas_Borodyhttp://en.wikipedia.org/wiki/National_Institutes_of_Healthhttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/Genetic_diversityhttp://en.wikipedia.org/wiki/Eastern_Africahttp://www.ijabpt.com/http://www.ijabpt.com/http://en.wikipedia.org/wiki/Barry_Marshallhttp://en.wikipedia.org/wiki/Robin_Warrenhttp://en.wikipedia.org/wiki/Perth,_Western_Australiahttp://en.wikipedia.org/wiki/Car_batteryhttp://en.wikipedia.org/wiki/Nobel_Prize_in_Physiology_or_Medicinehttp://en.wikipedia.org/wiki/Nobel_Prize_in_Physiology_or_Medicinehttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Stomachhttp://en.wikipedia.org/wiki/Microbiological_culturehttp://en.wikipedia.org/wiki/Giulio_Bizzozerohttp://en.wikipedia.org/wiki/Walery_Jaworskihttp://en.wikipedia.org/wiki/Jagiellonian_Universityhttp://en.wikipedia.org/wiki/Krak%C3%B3whttp://en.wikipedia.org/wiki/Gastrichttp://en.wikipedia.org/wiki/Robin_Warrenhttp://en.wikipedia.org/wiki/Barry_Marshallhttp://en.wikipedia.org/wiki/Petri_disheshttp://en.wikipedia.org/wiki/Easterhttp://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/wiki/Spicehttp://en.wikipedia.org/wiki/Endoscopyhttp://en.wikipedia.org/wiki/Gastroenterologyhttp://en.wikipedia.org/wiki/Thomas_Borodyhttp://en.wikipedia.org/wiki/National_Institutes_of_Healthhttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/Genetic_diversityhttp://en.wikipedia.org/wiki/Eastern_Africahttp://www.ijabpt.com/


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E2$dem$o(o+/

At least (alf t(e )orldEs population is infected *y t(e *acterium, maing it t(e most )idespread

infection in t(e )orld$ Actual infection rates #ary from nation to nation, t(e people in underde#eloped countries (as muc( (ig(er infection rates t(an t(e de#eloped countries lie 9ort(

America, Australasiaetc$ )(ere rates are estimated to *e around 2&$ 'nfections are usually

acuired in early c(ild(ood in all countries$ !o)e#er, t(e infection rate of c(ildren in de#eloping

nations is (ig(er t(an in industrialiJed nations, pro*a*ly due to poor sanitary conditions$ 'nde#eloped nations it is currently uncommon to find infected c(ildren, *ut t(e percentage of

infected people increases )it( age, )it( a*out &0 infected for t(ose o#er t(e age of 70

compared )it( around 10 *et)een 1/ and 30 years$ (e (ig(er pre#alence among t(e elderly

reflects (ig(er infection rates )(en t(ey )ere c(ildren rat(er t(an infection at later ages$Pre#alence appears to *e (ig(er in African-Americanand !ispanicpopulations, alt(oug( t(is is

liely related to socioeconomic rat(er t(an racial factors$ (e lo)er rate of infection in t(e

de#eloped countries is largely attri*uted to (ig(er (ygiene standards and )idespread use of

anti*iotics$ Despite (ig( rates of infection in certain areas of t(e )orld, t(e o#erall freuency of!elico*acter pylori infection is declining$ !o)e#er, anti*iotic resistance is appearing in

!elico*acter pyloriI t(ere are already many metronidaJoleand clarit(romycinresistant strains in

most parts of t(e )orld&G$

!elico*acter pylori is contagious, alt(oug( t(e eHact route of transmission is not no)n$ Person-

to-person transmission *y eit(er t(e oral-oral or fecal-oral routeis most liely$ %onsistent )it(

t(ese transmission routes, t(e *acteria (a#e *een isolated from feces, sali#a and dental plaue of

some infected people$ ransmission occurs mainly )it(in families in de#eloped nations yet can

also *e acuired from t(e community in de#eloping countries$ !elico*acter pylori may also *e

transmitted orally *y means of fecal matter t(roug( t(e ingestion of )aste-tainted )ater, so a

(ygienic en#ironment could (elp decrease t(e ris of !elico*acter pylori infection

0$+#re ): Paho+e%es$s o& He($o!aer 2/(or$


http://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/Australasiahttp://en.wikipedia.org/wiki/Developed_countryhttp://en.wikipedia.org/wiki/African_Americanhttp://en.wikipedia.org/wiki/Hispanichttp://en.wikipedia.org/wiki/Antibiotic_resistancehttp://en.wikipedia.org/wiki/Metronidazolehttp://en.wikipedia.org/wiki/Clarithromycinhttp://en.wikipedia.org/wiki/Fecal-oral_routehttp://en.wikipedia.org/wiki/Feceshttp://en.wikipedia.org/wiki/Salivahttp://en.wikipedia.org/wiki/Dental_plaquehttp://www.ijabpt.com/http://www.ijabpt.com/http://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/Australasiahttp://en.wikipedia.org/wiki/Developed_countryhttp://en.wikipedia.org/wiki/African_Americanhttp://en.wikipedia.org/wiki/Hispanichttp://en.wikipedia.org/wiki/Antibiotic_resistancehttp://en.wikipedia.org/wiki/Metronidazolehttp://en.wikipedia.org/wiki/Clarithromycinhttp://en.wikipedia.org/wiki/Fecal-oral_routehttp://en.wikipedia.org/wiki/Feceshttp://en.wikipedia.org/wiki/Salivahttp://en.wikipedia.org/wiki/Dental_plaquehttp://www.ijabpt.com/


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Paho+e%es$s

(e earliest descriptions of t(e organism classified it as predominately eHtracellular, gram-

negati#e, flagellated, and motile$ +it( t(e ad#ancement of *ioc(emical tec(niues, ne)

information a*out t(e pat(ogenicity and #irulence factors of !elico*acter pylori (as emerged,

indicating t(at infection *y !elico*acter pylori reuires a compleH interaction of *ot( *acterial

and (ost factors$ 'n#estigators (a#e identified se#eral *acterial proteins necessary for coloniJationof t(e gastric mucosa *y !elico*acter pylori, including proteins acti#e in t(e transport of t(e

organism to t(e surface of t(e mucosa eg, flagellin, )(ic( is encoded on genes flaA and flaB5$

.nce in t(e presence of t(e gastric mucosa, *acteria induce a transient (ypoc(lor(ydria *y an

unno)n mec(anism $

(e urease enJyme produced *y t(e *acteria alters t(e microen#ironment of t(e organism to

facilitate coloniJation$ Ad(erence t(en occurs #ia interaction *et)een cell-surface glycolipids and

ad(esins specific to !elico*acter pylori$ (ere also appears to *e a role played *y proteins called

cecropins, )(ic( are produced *y !elico*acter pylori and in(i*it t(e gro)t( of competing

organisms, as )ell as *y a P-type adenosine trip(osp(atase, )(ic( (elps pre#ent eHcessi#e

alaliniJation of t(e microen#ironment *y urease$ .nce attac(ed to gastric mucosa, !elico*acter

pylori causes tissue inKury *y a compleH cascade of e#ents t(at depends on *ot( t(e organism and

t(e (ost$ !elico*acter pylori, lie all gram negati#e *acteria, (as in its cell )alllipopolysacc(aride, )(ic( acts to disrupt mucosal integrity$ Furt(ermore, !elico*acter pylori

release se#eral pat(ogenic proteins t(at induce cell inKury$ For eHample, t(e %agA protein,

produced *y cytotoHic-associated gene A cagA5, is a (ig(ly immunogenic protein t(at may *e

associated )it( more se#ere clinical syndromes, suc( as duodenal ulcer and gastric

adenocarcinoma alt(oug( t(is uestion is far from settled5$ (ere is increasing e#idence t(at%agA positi#ity is associated )it( an increased ris for distal, *ut not proHimal, gastric

adenocarcinoma$ 'n addition, protein products of t(e #acuolating cytotoHin A gene #acA5 and t(e

A gene induced *y contact )it( epit(elium iceA5 are no)n to *e associated )it( mucosal

inKury$ .nce coloniJation of t(e gastric mucosa (as taen place, t(e immunogenic properties of

!elico*acter pylori induce an inflammatory reaction )it( neutrop(ilic gastritis t(at ultimately

results in t(e clinical manifestations of t(e infection$ (is process is mediated *y (ost factors,

including interleuins 1, 2, 7, /, and 12I interferon gamma, tumor necrosis factor, and Blymp(ocytes and p(agocytic cells$ (ese factors mediate inKury t(roug( release of reacti#e

oHygen species and inflammatory cytoines$ !elico*acter pylori additionally appear to increase

t(e rate of mucosal-programmed cell deat( also no)n as apoptosis5 7G$

E&&es o% +asr$ 2h/s$o(o+/

'n addition to producing local inKury of gastric mucosa, !elico*acter pylori alters normal gastric

secretion$ 'nterestingly, t(e location and se#erity of t(e infection seem closely associated )it( t(e

ultimate clinical outcome, most liely *ecause of effects on gastric p(ysiology$

Many studies (a#e s(o)n t(at patients )it( a duodenal ulcer )(o are infected )it( !elico*acter

pylori (a#e an increased serum le#el of gastrin, )(ic( in turn leads to increased acid output$

(ese patients tend to (a#e a milder p(enotypic eHpression of t(eir gastritis, )it( inflammation

mostly in t(e antrum or distal part of t(e stomac($


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'n contrast, patients )it( gastric adenocarcinoma, a no)n complication of !elico*acter pylori

infection tend to (a#e pangastritis )it( in#ol#ement of t(e acid secreting *ody of t(e stomac( as

)ell as t(e antrum$ (is condition leads to atrop(y of parietal cells )(ic( are responsi*le for

producing acid5 and gastrin-producing cells of t(e antrum )(ic( stimulate acid secretion5 and

e#entually produces ac(lor(ydria$ Patients )it( gastric adenocarcinoma also (a#e impaired acid

secretion in response to stimulation )it( gastrin LG$

Paho(o+$ &$%d$%+sAlt(oug( eHtensi#e )or (as *een performed to classify (istopat(ologic c(anges seen )it(

!elico*acter pylori infection, t(ere is no consensus on classificationI t(e Sydney system and t(e

!ouston ;astritis +ors(op system (a#e, (o)e#er, *een recogniJed as models$ AftercoloniJation, t(ere appears to *e an intense neutrop(ilic infiltrate in t(e necs of t(e mucosal

glands$ pit(elial c(anges are common )(en t(ere is irregularity of t(e surface arc(itecture, and

atrop(y of t(e glands is typical of longstanding infection$ Moreo#er, t(ere is usually lymp(ocytic

infiltration of t(e stroma and impaired mucus secretion$ Finally, areas of patc(yintestinal

metaplasia may *e seen, )(ic( are central to t(e de#elopment of neoplasia /G$

C($%$a( ma%$&esa$o%s3asr$$s a%d +asr$ a%er

.nce infected )it( !elico*acter pylori, most persons remain asymptomatic$ Some infected

persons may e#en clear t(e infection, )it( serore#ersion rates commonly reported to *e in t(erange of & to 10I it is not no)n if t(is serore#ersion is spontaneous or results from

elimination of t(e organism *y anti*iotic agents used to treat ot(er conditions$ !o)e#er, t(e

typical course of disease in infected patients *egins )it( c(ronic superficial gastritis, e#entually

progressing to atrop(ic gastritis$ (is progression appears to *e a ey e#ent in t(e cellular

cascade t(at results in t(e de#elopment of gastric carcinoma$ Histing data indicate a :0-fold

increase in rates of gastric carcinoma in patients )it( se#ere, multifocal atrop(ic gastritis,

compared )it( normal controls$ (e mec(anism of tumorigenesis appears to in#ol#e D9A

damage induced *y different cytoines and free radicals released in t(e setting of c(ronic

inflammation in suscepti*le persons$ Alt(oug( !elico*acter pylori is associated )it( t(e

de#elopment of adenocarcinoma of t(e antrum and *ody of t(e stomac(, it is also clearly lined

)it( gastric mucosaQassociated lymp(oid tissue MA65 lymp(omas$ !elico*acter pylori

stimulates lymp(ocytic infiltration of t(e mucosal stromaI t(is infiltration may act as a focus forcellular alteration and proliferation, ultimately resulting in neoplastic transformation to

lymp(oma$ 't appears t(at !elico*acter pylori also produces proteins t(at stimulate gro)t( of

lymp(ocytes in t(e early stages of neoplasia$ Most tellingly, it (as *een reported t(at regression

of lo)-grade gastric MA6 lymp(oma can *e ac(ie#ed in L0 to :0 of patients )it(eradication of !elico*acter pylori infection$ 8ecent )or (as s(o)n endoscopic ultrasound

eHamination to *e in#alua*le in identifying t(e grade of MA6 lymp(oma and in predicting t(e

efficacy of treating t(e !elico*acter pylori infection to o*tain regression of t(e lymp(oma :G$

Pe2$ #(er d$sease(e relations(ip *et)een !elico*acter pylori infection and peptic ulcer disease (as *een studied

eH(austi#ely, and it is no) accepted t(at t(e organism is t(e maKor cause, *ut not t(e only cause,

of peptic ulcer disease )orld)ide$ radicating t(e infection can alter t(e natural course of peptic

ulcer disease *y dramatically reducing its recurrence rate in treated patients, compared )it(untreated patients$ (is reduction occurs in patients )it( duodenal and gastric ulcers t(at (a#e no

(istory of nonsteroidal anti-inflammatory drug use$




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(e mec(anism *y )(ic( !elico*acter pylori induces peptic ulcer disease is incompletely

understood *ut most liely in#ol#es a com*ination of genetic predisposition of t(e (ost, #irulence

factors of t(e organism eg, acA and %agA proteins5, mec(anical damage to t(e mucosa, and

alterations of gastric and duodenal secretions

No%"#(er d/s2e2s$a9on-ulcer dyspepsia comprises a constellation of #aried symptoms, including dysmotility-lie,

ulcer-lie, and refluH-lie symptoms$ Many possi*le causes (a#e *een suggested for non-ulcerdyspepsia, including lifestyle factors, stress, altered #isceral sensation, increased serotonin

sensiti#ity, alterations in gastric acid secretion and gastric emptying, and !elico*acter pylori

infection$ A recent study also (ig(lig(ted t(e role played *y psyc(osocial impairment eg,

depression, somatiJation, anHiety5 in patients )it( non-ulcer dyspepsia$ 'n a study lining

!elico*acter pylori infection to non-ulcer dyspepsia, patients )it( t(e latter condition )ere t)ice

as liely to *e positi#e for t(e organism$ !o)e#er, despite suc( epidemiologic e#idence,

treatment studies (a#e failed to consistently s(o) t(at eradication of !elico*acter pylori results

in impro#ement of non-ulcer dyspepsia symptoms$ %onseuently, eradication of t(e organism can

not *e considered t(e standard of care in all patients )it( non-ulcer dyspepsia, *ecause

!elico*acter pylori infection is only a single part of t(e multi-factorial etiology of t(e disease10G

3asroeso2ha+ea( re&(#4 d$seaseMuc( attention (as *een focused on t(e possi*le relations(ip *et)een infection )it( !elico*acter

pylori and gastroesop(ageal refluH disease ;8D5 in its #arious manifestations eg, esop(agitis,

BarrettRs esop(agus5$ Some in#estigators (a#e suggested a lin *et)een t(e presence of

!elico*acter pylori and a decreased ris for de#eloping esop(agitis and BarrettRs esop(agusI

alt(oug( t(is in#erse association is supported *y many pre#alence studies, ot(ers fail to s(o) it$Studies (a#e also indicated t(at certain strains of !elico*acter pylori, nota*ly t(e %agA- positi#e

strain, may *e protecti#e against t(e de#elopment of BarrettRs esop(agus$ Moreo#er, 6a*enJ and

colleagues (a#e s(o)n t(at t(e incidence of esop(agitis may in fact, increase after eradication of

t(e organism$ reatment of !elico*acter pylori infection can lead to eHacer*ation of ;8D in

many patients, prompting many gastroenterologists to defer endoscopic antral *iopsies in patients

)it( significant ;8D and a*sent ulcer$ %on#ersely, ot(er studies using endoscopic findings, p!

pro*e measurements, and (istology to determine t(e presence of !elico*acter pylori did not findany association *et)een ;8D in any of its manifestations5 and infection )it( !elico*acter

pylori$ %learly, more definiti#e studies are necessary to define t(e relations(ip, if any, *et)een

t(ese 2 entities 11G$

Oher d$sease asso$a$o%s'n#estigators (a#e furt(er postulated a relations(ip *et)een !elico*acter pylori infection and

cardio#ascular disease and iron-deficiency anemia$ (ese associations, (o)e#er, reuire muc(

more study *efore a causal relations(ips is esta*lis(ed 12G$

D$a+%os$ es$%+%urrently, t(ere are se#eral popular met(ods for detecting t(e presence of !elico*acter pylori

infection, eac( (a#ing its o)n ad#antages, disad#antages, and limitations$ Basically, t(e tests

a#aila*le for diagnosis can *e separated according to )(et(er or not endoscopic *iopsy is

necessary$ !istological e#aluation, culture, polymerase c(ain reaction P%85, and rapid ureasetests are typically performed on tissue o*tained at endoscopy$ Alternati#ely, simple *reat( tests,

serology, and stool assays are sometimes used, and trials in#estigating P%8 amplification of

sali#a, feces, and dental plaue to detect t(e presence of !elico*acter pylori are ongoing


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H$so(o+/!istologic e#aluation (as traditionally *een t(e gold standard met(od for diagnosing !elico*acter

pylori infection$ (e disad#antage of t(is tec(niue is t(e need for endoscopy to o*tain tissue$

6imitations also arise at times *ecause of an inadeuate num*er of *iopsy specimens o*tained orfailure to o*tain specimens from different areas of t(e stomac($ 'n some cases, different staining

tec(niues may *e necessary, )(ic( can in#ol#e longer processing times and (ig(er costs$

!o)e#er, (istologic sampling does allo) for definiti#e diagnosis of infection, as )ell as of t(e

degree of inflammation or metaplasia and t(e presencea*sence of MA6 lymp(oma or ot(er

gastric cancers in (ig(-ris patients$

C#(#reBecause !elico*acter pylori is difficult to gro) on culture media, t(e role of culture in diagnosis

of t(e infection is limited mostly to researc( and epidemiologic considerations$ Alt(oug( costly,time-consuming, and la*or intensi#e, culture does (a#e a role in anti*iotic suscepti*ility studies

and studies of gro)t( factors and meta*olism $

Po(/merase ha$% rea$o%

+it( t(e ad#ent of P%8, many eHciting possi*ilities emerged for diagnosing and classifying!elico*acter pylori infection$ P%8 allo)s identification of t(e organism in small samples )it(

fe) *acteria present and entails no special reuirements in processing and transport$ Moreo#er,

P%8 can *e performed rapidly and cost- effecti#ely, and it can *e used to identify different strainsof *acteria for pat(ogenic and epidemiologic studies$ As suggested earlier, P%8 also is *eing

e#aluated for its utility in identifying !elico*acter pylori in samples of dental plaue, sali#a, and

ot(er easily sampled tissues$ (e maKor limitation of P%8 is t(at relati#ely fe) la*oratories

currently (a#e t(e capa*ility to run t(e assay$ 'n addition, *ecause P%8 can detect segments of

!elico*acter pylori D9A in t(e gastric mucosa of pre#iously treated patients, false-positi#e

results can occur, and errors in (uman interpretation of *ands on electrop(oretic gels can lie)ise

lead to false-negati#e results

Ra2$d #rease es$%+

8apid urease testing taes ad#antage of t(e fact t(at !elico*acter pylori is a urease producingorganism$ Samples o*tained on endoscopy are placed in urea-containing mediumI if urease is

present, t(e urea )ill *e *roen do)n to car*on dioHide and ammonia, )it( a resultant increase in

t(e p! of t(e medium and a su*seuent color c(ange in t(e p! dependent indicator$ (is test (as

t(e ad#antages of *eing ineHpensi#e, fast, and )idely a#aila*le$ 't is limited, (o)e#er, *y t(e

possi*ility of false positi#e resultsI decreased urease acti#ity, caused eit(er *y recent ingestion of

anti*iotic agents, *ismut( compounds, proton pump in(i*itors, or sucralfate or *y *ile refluH, can

contri*ute to t(ese false-positi#e results

Urea !reah esA urea *reat( test similarly relies on t(e urease acti#ity of !elico*acter pylori to detect t(e

presence of acti#e infection$ 'n t(is test, a patient )it( suspected infection ingests eit(er14%-

la*eled or 13%- la*eled ureaI 13%- la*eled urea (as t(e ad#antage of *eing non radioacti#e and t(us

safer t(eoretically5 for c(ildren and )omen of c(ild*earing age$ "rease, if present, splits t(e ureainto ammonia and isotope-la*eled car*on dioHideI t(e car*on dioHide is a*sor*ed and e#entually

eHpired in t(e *reat(, )(ere it is detected$




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Besides *eing eHcellent for documenting acti#e infection, t(is test is also #alua*le for esta*lis(ing

a*sence of infection after treatment, an important consideration in patients )it( a (istory of

complicated ulcer disease )it( *leeding or perforation$ 'n addition, a urea *reat( testis relati#ely

ineHpensi#e )(ic(e#er isotope is used5, is easy to perform, and does not reuire endoscopy$

!o)e#er, if t(e patient (as recently ingested proton pump in(i*itors, anti*iotic agents, or *ismut(

compounds, a urea *reat( test can *e of limited #alue$ (erefore, at least 1 )ee s(ould separate

t(e discontinuing of antisecretory medications and testing for acti#e infection, and 4 )eess(ould separate treatment of !elico*acter pylori infection and testing for eradication of t(e

organism$ Moreo#er, eHcept for maKor medical centers or tertiary referral centers )(ere results

are usually a#aila*le in fe)er t(an 24 (ours, a urea *reat( test may *e furt(er limited *y aturnaround time of se#eral days or longer5 reuired for transport of samples and analysis *y

specialiJed la*oratories not present in many community settings 13G$

ero(o+$ ess'n response to !elico*acter pylori infection, t(e immune system typically mounts a response

t(roug( production of immunoglo*ulins to organism-specific antigens$ (ese anti*odies can *e

detected in serum or )(ole-*lood samples easily o*tained in a p(ysicianRs office$ (e presence of

'g; anti*odies to !elico*acter pylori can *e detected *y use of a *ioc(emical assay, and manydifferent ones are a#aila*le$ Serologic tests offer a fast, easy, and relati#ely ineHpensi#e means of

identifying patients )(o (a#e *een infected )it( t(e organism$ !o)e#er, t(is met(od is not auseful means of confirming eradication of !elico*acter pyloriI se#eral different samples and

c(anges in titers of specified amounts o#er time )ould *e needed$ 'n addition, fe) patients

*ecome truly seronegati#e, e#en after eradication of t(e organism$ 'n lo)-pre#alence populations,

serologic tests s(ould *e a second-line met(odology *ecause of lo) positi#e predicti#e #alue and

a tendency to)ard false-positi#e results$ Serologic tests may *e useful in identifying certain

strains of more #irulent !elico*acter pylori *y detecting anti*odies to #irulence factors associated

)it( more se#ere disease and complicated ulcers, gastric cancer, and lymp(oma 14G$

oo( a%$+e% es$%+Stool antigen testing is a relati#ely ne) met(odology t(at uses an enJyme immunoassay to detect

t(e presence of !elico*acter pylori antigen in stool specimens$ A cost effecti#e and relia*le

means of diagnosing acti#e infection and confirming cure, suc( testing (as a sensiti#ity and

specificity compara*le to t(ose of ot(er nonin#asi#e tests$ Tuestions remain regarding possi*lecross reacti#ity )it( ot(er !elico*acter species present in t(e intestines, *ut definiti#e studies are

lacing 1&G$

3e%era( d$a+%os$ 2r$%$2(es(e uestion, of )(ic( patients to test, )(en to test t(em and )(at test to use is still a trou*lingone for many p(ysicians$ "ltimately, t(e ans)er to t(ese uestions must *e *ased on patient

preference, cost, a#aila*ility of different tests, and positi#e and negati#e predicti#e #alues of

different tests )(ic( depend on t(e indi#idual patient population, including t(e pre#alence of

disorders caused *y !elico*acter pylori infection in t(e community5$ 9e#ert(eless, certain

principles of testing seem uni#ersal$ First, endoscopic met(ods of diagnosis s(ould *e used only

if t(e procedure is necessary to detect some ot(er condition *esides !elico*acter pylori infection$

Second, only t(ose patients in )(om treatment )ill mae a difference s(ould *e tested$

%onclusi#e e#idence does not eHist t(at eradication of t(e infection in patients )it( simpledyspepsia )ill relie#e symptoms, and testing of asymptomatic patients )it(out a (istory of

documented peptic ulcer disease is not )arranted$ esting can *e considered on a case *y case

*asis in patients )it( symptoms suggesti#e of peptic ulcer disease$


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Because treatment of !elico*acter pylori infection is definitely indicated in patients )it( acti#e

or pre#iously documented peptic ulcer disease, gastric MA6 lymp(oma, or family (istory of

gastric cancer, t(eir !elico*acter pylori status must *e clarified$ "rea *reat( and stool antigen

tests are t(e most cost-efficient tests to identify acti#e infection, *ut t(eir limitations must *e

considered$ Alt(oug( serology is an eHcellent, ineHpensi#e test to ascertain if someone )it( a

(istory of peptic ulcer disease and unno)n !elico*acter pylori status )arrants treatment,

endoscopy )it( tissue sampling in patients )it( a (istory of peptic ulcer disease can pro#idemore definiti#e diagnosis of !elico*acter pylori infection, as )ell as information a*out t(e

acti#ity of peptic ulcer disease and possi*ly ot(er factors at play including gastric carcinoma5$

Follo)-up testing )it( urea *reat( or stool antigen tests *ot( of )(ic( (a#e sensiti#ities andspecificities greater t(an :0 is necessary to document cure in patients )it( complicated peptic

ulcer disease e$g$ perforation, (emorr(age, o*struction or recurrent symptoms and s(ould *e

performed 4 )ees after completion of treatment 17G$

Ma%a+eme%

3e%era( reame% 2r$%$2(esDetermining t(e optimum treatment of !elico*acter pylori infection is difficult, *ecause t(e

organism li#es in an en#ironment not easily accessi*le to many medications and *ecause

emerging *acterial resistance presents an added c(allenge$ Moreo#er, many of t(e recommendedregimens are difficult for patients to tae, leading to pro*lems )it( complianceI specifically,

(a#ing to tae a large num*er of pills at least t)ice daily and coping )it( unpleasant ad#erse

effects do little to encourage patient cooperation$ Despite t(ese o*stacles, current regimens can

o*tain cure rates in eHcess of /& in most patient populations 1LG$

Pa$e% ma%a+eme% $% 2r$mar/ are(e maKority of patients infected )it( !elico*acter pylori present initially in primary care,

suffering from dyspeptic symptoms )it( or )it(out alarm symptoms$ (is is )(ere many of t(em

can and s(ould *e treated for t(e infection, e#en t(oug(, in t(e a*sence of endoscopy, t(e primary

care p(ysician may not (a#e an accurate diagnosis of t(e underlying disease pat(ology$ A furt(er

consideration is t(e increasing media, and (ence patient, a)areness of !elico*acter pylori, and its

relations(ip to diseases suc( as gastric cancer$ 'n t(is en#ironment, primary care p(ysicians need

to (a#e a clear understanding of t(e maKor role t(at t(ey play in t(e management of t(e infection$(e recommendations gi#en (ere are particularly rele#ant to management in primary care, *ut

many of t(em apply across clinical practice$ )o strongly recommended indications )(ic(

s(ould *e noted (ere as particularly rele#ant in primary care are patients )(o are first-degree

relati#es of gastric cancer patients and eradication t(erapy in response to patientsE )is(es afterfull consultation$ As recommended in t(e original Maastric(t %onsensus 8eport, a Utest and treatE

approac( s(ould *e offered to adult patients under t(e age of 4& years t(e age cut-off may #ary

locally according to t(e mean age of gastric cancer onset5 presenting in primary care )it(

persistent dyspepsia$ Se#eral studies (a#e since *een pu*lis(ed )(ic( support t(is

recommendation 1/G$

A%$!$o$ a+e%s%urrently, anti*iotic agents used to treat !elico*acter pylori infection are administered in

com*ination, )it( no single agent e#er used as monot(erapy *ecause of a lac of efficacy and t(epotential de#elopment of resistance$ MetronidaJole (as acti#ity independent of p!, *ut resistance

to t(e drug is common in many parts of t(e )orld$




11/15


(is pro*lem )it( resistance is ameliorated some)(at, (o)e#er, )(en t(e drug is used )it(

clarit(romycin$ MetronidaJole can (a#e unpleasant ad#erse effects e$g$ nausea5 and a disulfiram-

lie reaction to alco(ol ingestion is possi*le, alt(oug( eHceedingly rare$ %larit(romycin (as lo)er

rates of resistance approHimately LQ115 *ut is not acid sta*le, may cause dysgeusia and is

more eHpensi#e t(an ot(er anti*iotic agents$ 8esistance to amoHicillin is rare, *ut t(is drug

usually reuires t(e co-administration of a proton pump in(i*itor *ecause its acti#ity is p!-

dependent$ Finally, tetracycline (as t(e ad#antage of lo) cost and lo) occurrence of resistance*ut can cause discoloration of t(e teet( in c(ildren and p(otosensiti#ity reactions 1:G$

Ad#%$6e a+e%s(e most popular agents currently used in com*ination )it( anti*iotic agents to eradicate

!elico*acter pylori infection are t(e proton pump in(i*itors i-e omepraJole *eing t(e most

)idely studied drug$ .mepraJole acts not only *y directly in(i*iting *acterial microsomal

enJymes *ut also *y raising intra-gastric p!, t(us facilitating t(e action of anti*iotic agents,

reducing gastric secretions, and increasing anti*iotic concentrations in t(e stomac($ .t(er

adKuncti#e agents include (istamine receptor antagonists and ranitidine *ismut( citrate, )(ic( (as

anti-secretory properties in addition to t(e anti*acterial action of *ismut( i$e$ interruption of t(e

*acterial cell )all5$ 8anitidine *ismut( citrate is no longer a#aila*le 20G$

C#rre% re+$me%s

Presently, t(e most efficacious regimens include 2 anti*iotic agents and at least 1 adKuncti#eagent for 14 days$ 'n literature citation study carried out (as claimed adeuate cure rates )it( a L-

day course of uadruple t(erapy 2 anti*iotics, 2 adKuncti#e agents5, *ut ot(er studies (a#e not

confirmed t(is finding$ Most clinicians treat !elico*acter pylori infection )it( a triple drug or

e#en uadruple-drug approac($ (e 1::/ guidelines suggested t(e follo)ing 3 regimens to *e

optimal 21G$

15 Administration of a proton pump in(i*itor, clarit(romycin and eit(er metronidaJole oramoHicillin for 2 )ees

25 Administration of ranitidine *ismut( citrate t(is guideline preceded t(e drugRs)it(dra)al in t(e "nited States5, clarit(romycin and eit(er metronidaJole, amoHicillin, or

tetracycline for 2 )ees

35 A proton pump in(i*itor, *ismut(, metronidaJole and tetracycline for 2 )ees$ More

recent recommendations outlined in a postgraduate course offered *y t(e American;astroenterology Association propose t(e use of ne)er proton pump in(i*itors$ For

patients )(o fail initial triple-drug t(erapy, according to follo)-up testing, su*seuent

t(erapy s(ould in#ol#e using a different com*ination of a#aila*le anti*iotic agents,

increasing t(e duration of treatment, or incorporating a course of uadruple t(erapy$

%ulture )it( sensiti#ity testing s(ould *e performed after 2 treatment failures 22G$

Emer+$%+ hera2$es

A%$!$o$s a%d oher a+e%sAs emerging drug resistance continues to plague efforts to eradicate !elico*acter pylori infection,

ne) t(erapeutic regimens incorporating eHisting anti*iotic agents and ne)ly de#eloped

compounds are essential$ 9itaJoHanide (as promise as an effecti#e agent )(en used in

com*ination )it( omepraJole, and furt(er studies are ongoing$ 'n addition, macrolides ot(er t(an

clarit(romycin may play a role in future t(erapies$ (e mapping of t(e complete genome of!elico*acter pylori (as opened t(e door for a ne) era in c(emot(erapeutic drugs$ 't )ill no) *e

possi*le to de#elop agents t(at act on specific ey protein products #ital to sur#i#al of t(e*acterium 23G$




12/15


7a$%esPer(aps t(e most eHciting )or in t(e uest to eradicate !elico*acter pylori as a significant

(uman pat(ogen is in t(e area of #accine de#elopment$ (e fact t(at t(e organism is pre#alent

)orld)ide, is responsi*le for significant mor*idity and mortality, and is difficult and eHpensi#e to

eradicate maes it a prime target for #accine t(erapy$ Pioneering )or in t(e early 1::0spro#ided e#idence t(at #accination against !elico*acter pylori infection )as possi*le, *ased on

murine models$ 't )as later learned t(at t(e ey mec(anism of protecti#e immunity against t(e

organism occurred #ia stimulation of -(elper type 2 p(enotype cells, )(ic( are induced *y t(e

production of interleuins 4 and 10 and not *y anti*ody production$ Se#eral issues remain in

regard to a safe and effecti#e #accine against !elico*acter pylori infection$ 'n t(e first place, a

safe mucosal adKu#ant or #ector to stimulate an immune response must *e identified$ Different

agents, including c(olera toHin and an sc(eric(ia coli (eat la*ile toHin, (a#e *een used in

conKunction )it( specific !elico*acter pylori antigens e$g$ urease5 )it( #arying success$Attenuated li#e #accines, including strains of Salmonella, used in com*ination )it( !elico*acter

pylori antigens (a#e s(o)n promise$ Secondly, t(e optimal route of administration needs to *e

definedI studies in mice s(o) promise )it( nasal and rectal routes, )(ic( )ould a#oid t(e

possi*le post immuniJation gastritis liely )it( an oral route$ 'n addition, different regimens needto *e de#eloped to ensure complete steriliJation of t(e gastric mucosaI t(e latter step (as not

generally *een attempted in murine models 24G$

Pre6e%$o%

!elico*acter pylori is a maKor cause of diseases of t(e upper gastrointestinal tract$ radication of

t(e infection in indi#iduals )ill impro#e symptoms including dyspepsia, gastritis and peptic

ulcers, and may pre#ent gastric cancer$ 8ising antimicro*ial resistanceincreases t(e need for a

pre#ention strategy for t(e *acteria$ (ere (a#e *een eHtensi#e #accine studies in mouse models,

)(ic( (a#e s(o)n promising results$ 8esearc(ers are studying different adKu#ants,antigens androutes of immuniJation to ascertain t(e most appropriate system of immune protection, )it( most

of t(e researc( only recently mo#ing from animal to (uman trials 2&G$

An intramuscular #accine against !elico*acter pylori infection is undergoing P(ase ' clinical

trialsand (as s(o)n an anti*ody response against t(e *acterium$ 'ts clinical usefulness reuiresfurt(er study 27G$

Studies (a#e recently *een pu*lis(ed suggesting t(at !elico*acter pylori acti#ity could *e

suppressed #ia dietary met(ods$ A 200: Napanese study in %ancer Pre#ention 8esearc( found t(at

eating as little as L0 g 2$& ounces5 of*roccoli sproutsdaily for t)o mont(s reduces t(e num*er

of colonies of !elico*acter pylori *acteria in t(e stomac( *y 40 in mice and (umans$ (is

treatment also seems to (elp *y en(ancing t(e protection of t(e gastric mucosa against

!elico*acter pylori *ut is relati#ely ineffecti#e on related gastric cancers$ (e pre#ious infection

returned )it(in t)o mont(s after *roccoli sprouts )ere remo#ed from t(e diet, so an ongoinginclusion in t(e diet is *est for continued protection from !elico*acter pylori 2LG$

A 200/ study pu*lis(ed in Oorean Nournal of Micro*iology and Biotec(nology found t(atimc(i

fermented ca**age5 contains a *acterium strain


13/15


(e *acterium strain isolated from imc(i,designated 6*$ plantarum 9.1, )as found to reduce

t(e urease acti#ity of !elico*acter pylori *y 40-70 and suppress t(e latter *acteriaEs *inding to

(uman gastric cancer cell line *y more t(an 33$ A 200: study (as found t(at green tea canpre#ent inflammation if ingested prior to eHposure to !elico*acter infection 2/G$

Her!a( reame% o& He($o!aer 2/(or$ $%&e$o%Many (undreds of plants )orld)ide are used in traditional medicine as treatment for *acterialinfections$ Some of t(ese (a#e also*een su*Kected to in #itro screening *ut t(e efficacy of suc(

(er*al medicines (as seldom *een rigorously tested in controlled clinical trials$ %on#entional

drugs usually pro#ide effecti#eanti*iotic t(erapy for *acterial infections *ut t(ere is anincreasing

pro*lem of anti*iotic resistance and a continuing need for ne) solutions$ Alt(oug( natural

products are not necessarily safer t(an synt(etic anti*iotics, some patients prefer to use (er*al

medicines$ (us (ealt(care professionals s(ould *e a)are of t(e a#aila*le e#idence for (er*al

anti*iotics$ (is re#ie) )as undertaen to assess critically t(ose anti*acterial (er*al medicines

t(at *een (a#e su*Kected to controlled clinical trials$ 'n a recent study, anti-!elico*acter pyloriacti#ity of &0 commonly used "nani traditional5 medicine plants from Paistan t(at are

eHtensi#ely utiliJed for t(e cure of gastrointestinal disorders to eHplore t(e natural source for pilot

compounds against !elico*acter pylori$ 2:G$

%urcumin is t(e su*stance t(at gi#es t(e spice turmeric its yello) color$ %urry po)der, )(ic( is

used eHtensi#ely in 'ndian cuisine, is largely made of turmeric and ot(er spices$ %urcumin

contains many po)erful antioHidants and anti-inflammatory compounds, )(ic( (a#e *een s(o)n

to support colon (ealt(, a (ealt(y cardio#ascular system, and most recently *rain (ealt($ DoJens

of studies (a#e s(o)n t(at it is a c(emo-pre#entati#e, and more recently it (as *een s(o)n to

eHert a strong anti*acterial effect against !elico*acter pylori$ Studies carried furnis(ed results

s(o)ing a significant in #itro effect of its eHtracts against !elico*acter pylori, leading researc(ers

to conclude t(at curcumin could *e considered a #alua*le support in t(e treatment of t(e infection30G$

'n a recent study, researc(ers found t(at licorice eHtract produced a potent effect against strains of

!elico*acter pylori t(at are resistant against clarit(romycin, one of t(e anti*iotics typically used

in t(e t(ree anti*iotic treatment regimens$ (e aut(ors concluded t(at t(is study pro#ides (ope

t(at licorice eHtract can form t(e *asis for an alternati#e t(erapeutic agent against !elico*acter

pylori$ 8esearc( study *ased communication found t(at licorice eHtracts are also effecti#e against

!elico*acter pylori strains t(at are resistant to *ot( amoHicillin and clarit(romycin, maing t(em

#ia*le as c(emo pre#enti#e agents for peptic ulcer or gastric cancer in !elico*acter pylori

infected indi#iduals 31G$


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14/15


RE0ERENCE

1$ Anant(aris(nan 9, Oate $ !elico*acter pyloriV (e rap-idly c(anging scenario$ 'nV

%(attopad(yay O$ editor$ ;$'$Surgery annual$ ol$ &$ 9e) Del(iV By)ordI 1::/$ p$ 1-

20$

2$ %urrent uropean concepts in t(e management of !elico*acter pylori infection$ (e

Maastric(t %onsensus 8eport ;ut 1::LI-1V/-13$3$ Fisc(*ac( +$ Primary gastric lymp(oma of MA6V consid-erations of pat(ogenesis,

diagnosis and t(erapy$ %an N ;astroenterol 2000I1-V44D-&0$

4$ 9'! %onsensus %onference$ !elico*acter pylori and pep-tic ulcer disease$ N Am MedAssoc 1::4I)8)V7&-:$

&$ A*ra(am P, B(atia SN$ First national )ors(op on !elico*acter pyloriV position paper on!elico*acter pylori in 'ndia$ 'ndian N ;astroenterol 1::LI19VS2:-S33$

7$ andon 8$ Second national )ors(op on !elico*acter pyloriV %onsensus Statements-

reatment of !elico*acter pylori in peptic ulcer disease$ 'ndian N ;astroenterol 2000I

L$ 1VS3L$

/$ %(i*a 9, 8ao B, 8ademaer N+, !unt 8!$ Meta-analy-sis of t(e efficacy of anti*iotict(erapy in eradicating !elico*acter pylori$ Am N ;astroenterol 1::2I;8V1L17-2L$

:$ Peterson +6, ;ra(am DW, Mars(all B, Blaser MN, ;enta 8M, Olein PD et al$%larit(romycin as monot(erapy for eradication of !elico*acter pyloriV a randomiJed,

dou*le *lind trial$ Am N ;astroenterol 1::3I;;V1/70-4$

10$ Bard(an OD, Dallaire %, isold !, Duggan A$ 8anitidine *ismut( citrate )it(clarit(romycin for t(e treatment of duo-denal ulcer$ ;ut 1::LI-1V1/1-7$

11$ De Boer +A, ytgat ;9N$ (e *est t(erapy for !elico*acter pylori infection$ S(ouldefficacy or side effect profile deter-mine our c(oiceX Scand N ;astroenterol

1::&I


15/15


20$ !o)den %+, !unt 8!$ ;uidelines for t(e management of !elico*acter pylori infection-for and on *e(alf of t(e Ad (oc %ommittee on Practice Parameters of t(e American

%ollege of ;astroenterology$ Am N ;astroenterol 1::/IV2330-L$

21$ !arris A$ reatment of !elico*acter pylori$ Drugs of oday 1::LIV&:-77$

22$ DaKani Y, Olamut MN$ 9o#el t(erapeutic approac(es to gastric and duodenal ulcersV anupdate$ Hpert .pin 'n#estig Drugs 2000IV1&3L-44$

23$ !offman PS$ Anti*iotic resistance mec(anisms of !elico*acter pylori$ %an N;astroenterol 1:::I1V243-:$

24$ A(uKa , D(ar A, Bal %, S(arma MP$ 6ansopraJole and secnidaJole )it( clarit(romycin,amoHicilin or pefloHicin in t(e eradication of !elico*acter pylori in a de#eloping coun-

try$ Aliment P(armacol (er 1::/I1)V&&1-&$

2&$ ersalo#ic N, S(ortridge D, Oli*er O, ;riffy , Beyer N, Flamm 8O et al$ Mutations in 23Sr 89A are associated )it( clarit(romycin resistance in !elico*acter pylori$ Antimicro*

Agents %(emot(er 1::7I-

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10(Helicobacter Pylori an Introduction)