faktorfaktor risiko yang berhu 6450405056

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<table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='mso-cellspacing:0in;mso-yfti-tbllook:1184;mso-padding-alt:0in 0in 0in 0in'> <tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes'> <td rowspan=5 style='padding:0in 0in 0in 0in'> <img width=100 height=100 id="_x0000_i1028" src="http://skripsi.unnes.ac.id/skripsi_v1/asset/images/unnes.jpg" alt="http://skripsi.unnes.ac.id/skripsi_v1/asset/images/unnes.jpg"><o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> KEMENTERIAN PENDIDIKAN DAN KEBUDAYAAN<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:1'> <td style='padding:0in 0in 0in 0in'> UNIVERSITAS NEGERI SEMARANG<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:2'> <td style='padding:0in 0in 0in 0in'> Gedung H, Kampus Sekaran, Gunungpati, Semarang 50229<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:3'> <td style='padding:0in 0in 0in 0in'> Telepon: (024) 8508081, Fax. (024) 8508082; Email: <a href="mailto:[email protected]">[email protected]</a><o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:4;mso-yfti-lastrow:yes'>

<td style='padding:0in 0in 0in 0in'> Website <a href="http://www.unnes.ac.id">http://www.unnes.ac.id</a><o:p></o:p> </td> </tr></table>

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<h3>Data skripsimahasiswa Universitas Negeri Semarang<o:p></o:p></h3>

<table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='mso-cellspacing:0in;mso-yfti-tbllook:1184;mso-padding-alt:0in 0in 0in 0in'> <tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> NAMA<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : HANIK MURJAYANAH<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:1'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> NIM<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : 6450405056<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:2'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> PRODI<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : Kesehatan Masyarakat</str

ong><o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:3'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> JURUSAN<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : Ilmu Kesehatan Masyarakat<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:4'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> FAKULTAS<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : Ilmu Keolahragaan<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:5'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> EMAIL<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : Aliyyahramadhani pada domain yahoo.co.id<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:6'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> PEMBIMBING 1<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : dr. Arulita Ika Fibriana, M.Kes<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:7'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> PEMBIMBING 2<o:p></o:p>

</td> <td style='padding:0in 0in 0in 0in'> : dr. Yuni Wijayanti, M.Kes<o:p></o:p> </td> </tr> <tr style='mso-yfti-irow:8;mso-yfti-lastrow:yes'> <td width=150 style='width:112.5pt;padding:0in 0in 0in 0in'> TGL UJIAN<o:p></o:p> </td> <td style='padding:0in 0in 0in 0in'> : 2011-02-17<o:p></o:p> </td> </tr></table>

<h3>Faktor-FaktorRisiko yang Berhubungan dengan Kejadian Gastritis (Studi di RSU dr. R.Soetrasno Rembang Tahun 2010)<o:p></o:p></h3>

<h4>ABSTRAK<o:p></o:p></h4>

Permasalahan yang dikaji dalam penelitian ini adalah faktor risiko yangberhubungan dengan kejadian gastritis (studi di RSU.dr.R.Soetrasno Rembang).Tujuan dari penelitian ini adalah untuk mengetahui faktor-faktor risiko apasaja yang berhubungan denagn kejadian gastritis di RSU.dr.R.Soetrasno Rembang. Jenis penelitian ini adalah penelitian analitik dengan rancangan penelitiancase control. Populasi dalam penelitian ini terdiri dari kasus dan kontrol.Sampel yang diambil sejumlah 28 kasus (penderita) dan 56 kontrol (bukanpenderita) yang diperoleh berdasarkan perolehan sampel minimal. Instrumen yangdigunakan dalam penelitian ini adalah kuesioner, catatan medik, lembarobservasi. Data primer diperoleh dengan wawancara, pengamatan, dan pengukuran.Data sekunder diperoleh dari catatan medik di RSU.dr.R.Soetrasno Rembangmengenai kejadian gastritis. Analisis data dilakukan dengan cara univariat danbivariat (menggunakan uji chi square dengan α=0,05). D�ri hasil penelitian didapatkan hasil faktor-faktor risiko yang berhubungandengan kejadian gastritis adalah umur (p=0,0001, OR=17,333), jenis kelamin(p=0,018, OR=3,059), riwayat mengkonsusmsi makanan yang merangsang peningkatanasam lambung (p=0,001, OR=4,843), riwayat adanya stres psikis (p=0,013,OR=3,240), riwayat mengkonsusmsi obat yang mengiritasi lambung (p=0,003,OR=4,129). Sedangkan faktor yang tidak berhubungan dengan kejadian gastritisadalah status ekonomi (p=0,877, OR=0,931), perilaku yang berisiko tertularHelicobacter pylori (p=0,867, OR=1,087), kondisi jamban (p=0,593, OR=1,323). Saran yang dapat diberikan bagi rumah sakit agar meningkatkan pelayanan medisterutama bagi para pasien gastritis, sehingga prognosis dan perjalanan penyakitpada penderita tidak menjadi parah. Bagi masyarakat khususnya penderitagastritis agar lebih meningkatkan upaya untuk melakukan pencegahan denganmemperhatikan diet makanan yang disesuaikan dengan tingkat keparahan penyakityang diderita dengan mengkonsultasikan terlebih dahulu kepada dokter. Bagipeneliti selanjutnya perlu adanya penelitian lanjutan dengan menambah faktorlain yang berpengaruh terhadap kejadian gastritis seperti pengetahuan, merokok

dsb. -------------------------------------------------> The problem reviewed in this research was the risk factors correlated withgastritis incidence (A study in Public Hospital dr. R. Soetrasno, Rembang). Thecurrent study aimed at discovering the risk factors correlated with gastritisincidence in Public Hospital dr. R. Soetrasno, Rembang. =0.05).<spanstyle='mso-char-type:symbol;mso-symbol-font-family:"Times New Roman"'>�Thisstudy was one of analytical research using case-control research design. Thepopulation of this research consisted of case and control. The sample taken was28 case (patient) and 56 control (non-patient) obtained by a minimum sampling.The instruments used in this research were questionnaire, medical record, andobservation sheet. The primary data is obtained using interview, observation,and measurement. The seconday ones were obtained from medical records in PublicHospital dr. R. Soetrasno, Rembang, on gastritis incidence. The data wereanalyzed in univariate and bivariate fashions (using chi square test with From the research result, it was found that the risk factors correlated withgastritis incidence were age (p=0.0001, OR=17.333), sex (p=0.018, OR=3.059),history on the consumption of gastric acid increase stimulating foods (p=0.001,OR=4.843), history on psychological stress (p=0.013, OR=3.240), history ongastric-iritating medicine consumption (p=0.003, OR=4.129). Meanwhile, thefactors uncorrelated with gastritis incidence, were economic status (p=0.877,OR=0.931), risky behaviors of being infected with Helicobacter pylori (p=0.867,OR=1.087), and toilet condition (p=0.593, OR=1.323). The suggestion the researcher could offer was for the hospital to improve theirmedical service, particularly to gastritis patients, in order to prevent thedisease prognosis and progress in them from being severe. The society,gastritis patients in particular, were suggested to improve their preventionefforts by taking care of the diet meal adjusted to the severity level of thedisease suffered by consulting it in advance with a doctor. For furtherresearchers, it was necessary to have further research by adding other factorinfluencing the gastritis incidence such as knowledge and smoking habits, etc.

<h4>KATA KUNCI<o:p></o:p></h4>

Gastritis 

<h4>REFERENSI<o:p></o:p></h4>

A.B. Wardoyo, 1997, Waspadai Ancaman Kesehatan Kita, Solo: CV. Aneka Cipta. Ahmad. H. Asdie, 2002, Harrison Prinsip-Prinsip Ilmu Penyakit Dalam (HarrisonPrinciples Of Internal Medicine), Yogyakarta: Buku Kedokteran EGC. Arif Mansjoer, dkk, 2001, Kapita Selekta Kedokteran Edisi Ketiga Jilid Kedua,Jakarta: Media Aesculapius . Aru W. Sudoyo, 2006, Ilmu Penyakit Dalam, Jakarta: FK. UI A.R. Nasutlon, 1992, Efek Samping Obat Anti Inflamasi Non Steroid,http://www.kalbe.co.id/files/cdk/files/11EfekSamping078.pdf/11EfekSamping078.html,diakses 16 Maret 2010. Bhisma Murti, 2003, Prinsip Dan Metode Riset Epidemiologi, Yogyakarta: GajahMada University Press. Boedhi Darmojo, 2006, Geriatri, Edisi ke-3, cetakan ke-2, Jakarta: BalaiPenerbit FKUI. , 2006, Profil Kesehatan Indonesia 2006. www.depkes.go.id. diakses 22 Desember

2009. Dinkes Provinsi Jateng, 2005, Pedoman Teknis Penilaian Rumah Sehat UntukPuskesmas, Semarang: Dinkes Provinsi Jateng press. Dinkes Provinsi Jateng, 2009, Data Penyakit Gastritis Tahun 2008-2009 Di JawaTengah, Semarang: UKR Dinkes Propinsi Jawa Tengah. Endang Lanywati, 2001, Penyakit Maag dan Gangguan Pencernaan, Yogyakarta:Kanisius. Gubernur Jawa Tengah, 2008, Keputusan Gubernur Jawa Tengah No. 561.4/ 52/ 2008Tentang Upah Minuman Pada 35 ( tiga puluh lima) Kabupaten/ Kota Di PropinsiJawa Tengah Tahun 2009, Semarang: Gubernur Jawa Tengah. Ilmu Kesehatan Masyarakat, 2007, Pedoman Penyusunan Skripsi Mahasiswa ProgamStrata I, Semarang: UNNES Press. Kunadi Tanzil, 2005, Peran Helicobacter pylori Dan Epidemiologinya PadaPenyakit Saluran Cerna, Vol.4, Majalah Kedokteran Atmajaya. Marcellus Simadibrata K, Penyebab dan Diagnosa Pendarahan Saluran Cerna BagianAtas, Ethical Digest No. 78 Agustus 2010 hal 33 Nasrul Subir&Julius, Gambaran Endoskopi Saluran Cerna Bagian Atas Di BagianPenyakit Dalam Di RSU.dr. M.Jamil Padang, Cermin Dunia Kedokteran No.79. 1992:26 Nyoman Wibawa, 2004, Penanganan Dispepsia Pada Lanjut Usia.ejournal.uhud.ac.id/abstrak/penanganan%20dispepsia%20pd%20lansia% 20.PDF,diakses 25 November 2010. Ratna Yunita, 2009, Hubungan Antara Karakteristik Responden, Kebiasaan Makandan Minum, serta Pemakaian NSAID dengan Terjadinya Gastritis Pada MahasiswaKedokteran (Studi Di Klinik Keluarga Fakultas Kedokteran UNAIR), FKM UNAIRSurabaya. Ronal H. Sitorus, 1996, Pedoman Perawatan Dan Pengobatan Berbagai Penyakit,Bandung : Pionir Jaya. Slamet Suyono, 2001, Buku Ajar Ilmu Penyakit Dalam Jilid Dua Edisi Ketiga,Jakarta: Balai Penerbit FKUI. Sistem Informasi Statistik WHO, 2004, Mortalitas Gastritis dan DuodenitisMenurut Negara,http://www.nationmaster.com/graph/mor_gas_and_duo-mortality-gastritis-and-duodenitis.diakses 15 juli 2010. Soekidjo Notoadmodjo, 2005, Metodologi Penelitian Kesehatan, Jakarta: RinekaCipta Sopiyudin Dahlan, 2006, Seri Dua Besar Sampel Dalam Penelitian Kedokteran DanKesehatan, Jakarta: PT. ARKANS. Sudigdo Sastroasmoro, 2002, Dasar-Dasar Metodologi Penelitian Klinis, Jakarta:Sagung Seto. Sudaryat Suraatmaja, 2007, Kapita Selekta Gastroenterologi Anak, Jakarta: CV.Sagung Seto. Suharsimi Arikunto, 2002, Prosedur Penelitian Suatu Pendekatan Praktek,Jakarta: Rhineka Cipta. Sujono Hadi, 2002, Gastroenterologi, Bandung: P. T. ALUMNI Sylvia A. Price dan Wilson, 1995, Patofisiologi Konsep Klinis Proses-ProsesPenyakit Edisi 4, terjemahan Peter Anugerah, Jakrta: EGC. Tan Hoan Tjay&Kirana Rahardja, 2002, Obat-obat Penting: Khasiat,Penggunaan, dan Efek Sampingnya Edisi Ke-5, Jakarta: PT. Elex Media Komputindo. Terry Looker And Olga Gregson, 2005, Managing Stres, cetakan 1, terjemahanHaris Setiawati, Yogyakarta: BACA Unun Maulidiyah, 2006, Hubungan Antara Stress Dan Kebiasaan Makan DenganTerjadinya Kekambuhan Penyakit Gastritis : Studi Pada Penderita Gastritis DiBalai Pengobatan Dan Rumah Bersalin Mawaddah Kecamatan Ngoro KabupatenMojokerto, FKM UNAIR Surabaya Vera uripi, 2001, Menu Untuk Penderita Hepatitis Dan Gangguan SaluranPencernaan, cetakan 1, Jakarta: Puspa Swara. Vinay Kumar, et al, 2007, Robbins Buku Ajar Patologi Edisi 7, Terjemahan Brahn

U. Pendit, Jakarta: Buku Kedokteran EGC. Yvonne van THp Dynhoven dan Rob de Jonge , 2001, Transmisi Helicobacter pylori: Peran Untuk Makanan?, Vol.79, Buletin Organisasi Kesehatan Dunia,http://www.who.int/bulletin/archives/79(5)455.pdf diakses 26 Mei 2010.

<o:p> </o:p>

<ahref="http://www.slideshare.net/intertdihati/hubungan-antara-pola-makan-dengan-kejadian-gastritis-pada-mahasiswa-semester-ii-stikes-wira-husada-yogyakarta-2011">http://www.slideshare.net/intertdihati/hubungan-antara-pola-makan-dengan-kejadian-gastritis-pada-mahasiswa-semester-ii-stikes-wira-husada-yogyakarta-2011</a>(penelitian pola makan dan gastritis)

SEMINARSIN MEDICINE OF THE BETH ISRAEL HOSPITAL, BOSTON<o:p></o:p>

<p class=serieseditors style='margin:0in;margin-bottom:.0001pt;line-height:14.4pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;orphans: 2;text-align:-webkit-auto;widows: 2;-webkit-text-size-adjust: auto;-webkit-text-stroke-width: 0px;word-spacing:0px'>Jeffrey S. Flier, M.D., Editor,Lisa H. Underhill, Assistant Editor<o:p></o:p>

<h1 style='margin-top:0in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;background-attachment:initial;background-origin: initial;background-clip: initial;orphans: 2;text-align:-webkit-auto;widows: 2;-webkit-text-size-adjust: auto;-webkit-text-stroke-width: 0px;background-position:initial initial;background-repeat:initial initial;word-spacing:0px'>Pathogenesisof Peptic Ulcer and Implications for Therapy<o:p></o:p></h1>

<p class=authors style='margin:0in;margin-bottom:.0001pt;line-height:12.0pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;orphans: 2;text-align:-webkit-auto;widows: 2;-webkit-text-size-adjust: auto;-webkit-text-stroke-width: 0px;word-spacing:0px'>Andrew H. Soll, M.D.<o:p></o:p>

<p class=citationline style='margin:0in;margin-bottom:.0001pt;line-height:12.0pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;orphans: 2;text-align:-webkit-auto;widows: 2;-webkit-text

-size-adjust: auto;-webkit-text-stroke-width: 0px;word-spacing:0px'><span style='font-size:8.5pt;font-family:"Arial","sans-serif";mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:major-fareast;color:#666666;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>N Engl J Med 1990; 322:909-916<spanstyle='font-size:8.5pt;font-family:"Arial","sans-serif";color:#666666'><ahref="http://www.nejm.org/toc/nejm/322/13/" style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><spanstyle='color:#006892;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>March 29, 1990</a><spanstyle='font-size:8.5pt;font-family:"Arial","sans-serif";mso-fareast-font-family:Verdana;color:#666666;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>DOI: 10.1056/NEJM199003293221307<spanstyle='font-size:8.5pt;font-family:"Arial","sans-serif";color:#666666'><o:p></o:p>

Share:<o:p></o:p>

<div style='mso-element:para-border-div;border:solid #CCCCCC 1.0pt;border-bottom:none;mso-border-top-alt:solid #CCCCCC .75pt;mso-border-left-alt:solid #CCCCCC .75pt;mso-border-right-alt:solid #CCCCCC .75pt;padding:6.0pt 11.0pt 0in 8.0pt;background:white;margin-left:0in;margin-right:-.75pt'>

<p class=MsoNormal style='line-height:12.0pt;background:white;vertical-align:baseline;border:none;mso-border-top-alt:solid #CCCCCC .75pt;mso-border-left-alt:solid #CCCCCC .75pt;mso-border-right-alt:solid #CCCCCC .75pt;padding:0in;mso-padding-alt:6.0pt 11.0pt 0in 8.0pt'><span style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit;overflow-x: hidden;overflow-y: hidden;background-repeat:no-repeat;background-position-x:-30px;background-position-y:-34px'>Article<o:p></o:p>

<p class=MsoNormal style='margin-top:2.25pt;line-height:12.0pt;background:white;vertical-align:baseline;border:none;mso-border-top-alt:solid #CCCCCC .75pt;mso-border-left-alt:solid #CCCCCC .75pt;mso-border-right-alt:solid #CCCCCC .75pt

;padding:0in;mso-padding-alt:6.0pt 11.0pt 0in 8.0pt'>References<o:p></o:p>

<p class=MsoNormal style='line-height:12.0pt;background:white;vertical-align:baseline;border:none;mso-border-top-alt:solid #CCCCCC .75pt;mso-border-left-alt:solid #CCCCCC .75pt;mso-border-right-alt:solid #CCCCCC .75pt;padding:0in;mso-padding-alt:6.0pt 11.0pt 0in 8.0pt'>Citing Articles<spanclass=apple-converted-space> (48)<o:p></o:p>

<p class=MsoNormal style='margin-top:2.25pt;line-height:12.0pt;background:white;vertical-align:baseline;border:none;mso-border-top-alt:solid #CCCCCC .75pt;mso-border-left-alt:solid #CCCCCC .75pt;mso-border-right-alt:solid #CCCCCC .75pt;padding:0in;mso-padding-alt:6.0pt 11.0pt 0in 8.0pt'>Letters<o:p></o:p>

</div>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>ALTHOUGH several features of peptic ulcer disease have beenelucidated over the past few years, new questions have replaced those that havebeen answered. Some of the factors that may predispose people to thedevelopment of peptic ulcers have been identified, but how they produce theireffects and how they can be combated therapeutically remain unclear. Thisseminar briefly reviews current knowledge about the pathogenesis of pepticulcers and discusses strategies for treatment.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleDefense of Normal Mucosa against Acid and Peptic Injury"><spanstyle='font-size:10.5pt;font-family:"Arial","sans-serif";color:#333333;text-transform:uppercase'>DEFENSE OF NORMAL MUCOSA AGAINST ACID AND PEPTICINJURY<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><span style='font-size:9.5pt;font-family:"Arial","sans-serif";

color:#333333'>Three basic levels of defense underlie the remarkable ability ofnormal gastroduodenal mucosa to resist injury from the acid and peptic activityin gastric juice. Surface epithelial cells secrete mucus and bicarbonatecreating a pH gradient in the mucus layer from the very acidic gastric lumen tothe nearly neutral surface of the mucosa.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref1"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>1</a><spanclass=apple-converted-space> Gastric mucosal cells have a specializedapical-surface membrane that resists the diffusion of acid back into the cell.This can be shown in vitro by mounting in an Ussing chamber a monolayer ofcanine fundic chief cells in primary culture. When the apical surface of thecells is bathed in acidic medium, the monolayer increases in electrical resistanceand maintains integrity to an apical pH of about 2.0. In contrast, themonolayer rapidly deteriorates when the basolateral surface is exposed to a pHbelow 5.5.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref2"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>2</a><spanclass=apple-converted-space> Although acidification has been found toincrease electrical resistance in other epithelia, the magnitude of changereported in these other cell types is not as great as that shown by chief-cellmonolayers. Additional studies are needed to provide a direct comparison withother epithelial cells and to examine the nature of the specialization thatallows the apical membrane of gastric epithelial cells to resist an acidenvironment. In addition, mucosal cells may directly resist injury by intrinsicmechanisms, such as the extrusion of back-diffused hydrogen ions by means ofbasolateral carriers (e.g., sodium—hydrogen or sodium—bicarbonate exchange).The rapid repair of injury is essential to maintaining mucosal integrity;surface epithelial cells continually slough, and the gaps are resealed byadjacent cells that move to fill them and by cell replication in response tostill unknown trophic signals.<span

style='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref3"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>3</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Bloodflow in normal mucosa removes the acid that has diffused across a compromisedmucosa. Prostaglandins enhance the mucosa's resistance to injury under certainconditions, perhaps by maintaining mucosal blood flow and stimulating thesecretion of mucus and bicarbonate.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleAcid Secretion and Peptic Ulcers">ACIDSECRETION AND PEPTIC ULCERS<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>The formation of peptic ulcers depends critically on thepresence of acid and peptic activity in gastric juice. About a third ofpatients with duodenal ulcer, but not gastric ulcer, secrete excess gastricacid.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> In most of these patients, the excess canbe attributed to an increase in the mass of acid-secreting gastric mucosa. In asmall number of patients with duodenal ulcer, the hypersecretion of acid mayreflect an increase in basal acid secretion due to vagal overactivity. Theregulation of acid secretion and the suspected abnormalities in peptic ulcerdisease have recently been reviewed.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref5"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:

inherit;font-style:inherit'>5</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'><o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Schwartz's dictum "no acid — no ulcer"<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref6"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>6</a><spanclass=apple-converted-space> is more accurate if amplified to "noacid and peptic activity —no ulcer." Peptic activity is an indispensablecomponent of the pathogenesis of ulcers; acid without pepsin has littledigestive power.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref7"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>7</a><spanclass=apple-converted-space> Pepsin is secreted as its precursor,pepsinogen, which is activated only in an acidic environment<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref7"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>7</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>; itsproteolytic activity is reduced above pH 3.5, and it is irreversiblyinactivated above pH 6.0. Pepsinogen and pepsin are members of a family ofheterogeneous isozymogens and isozymes.<span style='border-style:initial;

border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref7"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>7</a><spanclass=apple-converted-space> Although this heterogeneity has providedfascinating material for genetic studies, its biologic importance is unclear,as are the effects of two other acid proteases in the stomach, cathepsin D andcathepsin E. The near total dependence of peptic ulcer on acid and pepticactivity is supported by the therapeutic effects of the antisecretory drugomeprazole, which completely inhibits the secretion of acid by blocking thehydrogen—potassium adenosinetriphosphatase. Omeprazole (40 mg daily) healspeptic ulcers that have not responded to prolonged conventional therapy.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref8"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>8</a><spanclass=apple-converted-space> However, these ulcers rapidly recur whentherapy is stopped, reflecting the noncurative nature of antisecretory therapy.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleImpaired Mucosal Defense"><spanstyle='font-size:10.5pt;font-family:"Arial","sans-serif";color:#333333;text-transform:uppercase'>IMPAIRED MUCOSAL DEFENSE<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>The development of peptic ulcer requires acid and pepticactivity plus a breakdown in mucosal defense, as Schwartz recognized in 1910when he stated that "peptic ulcer is a product of self-digestion; itresults from an excess of autopeptic power in gastric juice over the defensivepower of gastric and intestinal mucosa."<span style='border-style:

initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref6"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>6</a><spanclass=apple-converted-space> The pathogenesis of peptic ulcer is oftendepicted as a balance in which a small shift in the standoff between acidsecretion and mucosal defense tips the equilibrium toward health or ulcers.Although occasional ulcers result from large increases in the secretion ofacid, and acid and peptic activity is critical to the formation of ulcers,peptic ulcers generally develop only when mucosal defense is also perturbed.Two major factors appear to disrupt mucosal resistance to injury: nonsteroidalantiinflammatory drugs (NSAIDs) and <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>Helicobacter pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>(formerly<emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>Campylobacter pylori) infection. Specific defectsin mucosal defense have been hypothesized. The duodenal secretion ofbicarbonate is impaired in patients with duodenal ulcer,<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref9"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>9</a><spanclass=apple-converted-space> but whether this defect is primary orsecondary to other factors, such as <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'><span style='font-size:10.0pt;font-family:"Arial","sans-serif";

color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>H. pylori—induced duodenitis or gastric metaplasia,remains uncertain. The production of prostaglandins may be abnormal in personswith peptic ulcer, but no consistent abnormality has been confirmed. On thebasis of these considerations, the model depicted in<spanclass=apple-converted-space> <ahref="http://www.nejm.org/action/showImage?doi=10.1056%2FNEJM199003293221307&iid=f001"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Figure1</a><spanclass=figuretitle>FIGURE 1<spanstyle='border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/action/showImage?doi=10.1056%2FNEJM199003293221307&iid=f001"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><!--[if gte vml 1]><v:shapetype id="_x0000_t75" coordsize="21600,21600" o:spt="75" o:preferrelative="t" path="m@4@5l@4@11@9@11@9@5xe" filled="f" stroked="f"> <v:stroke joinstyle="miter"/> <v:formulas> <v:f eqn="if lineDrawn pixelLineWidth 0"/> <v:f eqn="sum @0 1 0"/> <v:f eqn="sum 0 0 @1"/> <v:f eqn="prod @2 1 2"/> <v:f eqn="prod @3 21600 pixelWidth"/> <v:f eqn="prod @3 21600 pixelHeight"/> <v:f eqn="sum @0 0 1"/> <v:f eqn="prod @6 1 2"/> <v:f eqn="prod @7 21600 pixelWidth"/> <v:f eqn="sum @8 21600 0"/> <v:f eqn="prod @7 21600 pixelHeight"/> <v:f eqn="sum @10 21600 0"/> </v:formulas> <v:path o:extrusionok="f" gradientshapeok="t" o:connecttype="rect"/> <o:lock v:ext="edit" aspectratio="t"/></v:shapetype><v:shape id="Picture_x0020_3" o:spid="_x0000_i1027" type="#_x0000_t75" alt="http://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/1990/nejm_1990.322.issue-13/nejm199003293221307/production/images/small/nejm199003293221307_f1.gif" href="http://www.nejm.org/action/showImage?doi=10.1056%2FNEJM199003293221307&am

p;iid=f001" style='width:83.25pt;height:62.25pt;visibility:visible;mso-wrap-style:square' o:button="t"> <v:imagedata src="faktorfaktor_risiko_yang_berhu_6450405056_files/image001.gif" o:title="nejm199003293221307_f1"/></v:shape><![endif]--><![if !vml]><imgborder=0 width=111 height=83src="faktorfaktor_risiko_yang_berhu_6450405056_files/image001.gif"alt="http://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/1990/nejm_1990.322.issue-13/nejm199003293221307/production/images/small/nejm199003293221307_f1.gif"v:shapes="Picture_x0020_3"><![endif]></a><spanclass=figurecaption>A Model of the Pathogenesis of Peptic Ulcer.<spanclass=apple-converted-space> appears to be more appropriate for thepathogenesis of peptic ulcer than the traditional seesaw model of acid versusmucosal defense.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articlePredisposing Factors for Peptic Ulceration">PREDISPOSINGFACTORS FOR PEPTIC ULCERATION<o:p></o:p></h3>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleH. pylori Infection"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>H.pylori Infection<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>infectionof the gastric antrum is associated with an inflammatory response.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><span style='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;

mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref10"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>10</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref11"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>11</a><spanclass=apple-converted-space> A causal association is likely, but someargue that acute gastritis due to some other cause may predispose patients to<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>colonization.Acute, symptomatic gastritis has occurred in normal volunteers inadvertentlyexposed to <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori; although biopsies indicated the presenceof <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>H.pylori, the lack of biopsies before exposure made it impossible toestablish causality. A causal relation is supported by the finding thateradicating <em

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>bytreatment with colloidal bismuth, tinidazole, or other agents is associatedwith the resolution of the acute gastritis, whereas treatment without theeradication of the organism does not decrease polymorphonuclear counts.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref13"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>13</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref14"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>14</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref15"

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>15</a><spanclass=apple-converted-space> Koch's postulates about the induction ofgastritis by <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>could betested by administering the organism to persons with histologically normalmucosa, but since <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>can bedifficult to eradicate, such a study cannot be justified. Animal models mayeventually provide insight into the mechanisms of the disease,<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref16"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>16</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>but atpresent, the exact relation between <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>andpeptic disease must be inferred indirectly.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Antral gastritis has been found in nearly all patients with

gastric or duodenal ulcer.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref10"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>10</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref13"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>13</a><spanclass=apple-converted-space> <sup style='border-style:initial;border-color

:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref15"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>15</a><spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> has been found in the antrum of more than95 percent of the patients with duodenal ulcer and in at least 75 percent ofthose with gastric ulcer.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref10"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>10</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;

border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref11"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>11</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref13"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>13</a><spanclass=apple-converted-space> However, about 50 percent of the patientswith dyspepsia but no macroscopic ulceration (ulcer-negative dyspepsia) alsohave <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>H.pylori <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>infection,and about 20 percent of healthy volunteers have the bacteria. Furthermore, theoccurrence of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>in thehealthy population is age-dependent, with older persons more likely to have theorganism.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;

border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Recently, interest has focused on the mechanisms by which<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> could promote peptic ulceration. Theinflammatory response associated with the organism disrupts the mucosalarchitecture and defense mechanisms, which could predispose to pepticulceration. However, <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>couldalso produce toxins that directly damage the mucosa or promote ulceration inother ways. Certain strains of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>may bemore pathogenic than others. Less is known about<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> in the duodenum than in the antrum ofpatients with peptic ulcer.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref17"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>17</a><span

class=apple-converted-space> It is interesting to note, however, that<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> only overlies mucosa with gastricmetaplasia.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref17"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>17</a><spanclass=apple-converted-space> The specific factors that account for theadherence of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>to thegastric cells in the duodenum are critical to understanding the infection, butthey have not been elucidated. <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>couldinduce duodenitis in these areas of gastric metaplasia, thus disrupting thestructure and function of the mucosa and perhaps predisposing to ulceration.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;

outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Although <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>infectionmay explain some of the mysteries of peptic ulcer disease, the association alsoposes the question of why ulcers develop in a very small percentage of thepeople who harbor the organism. Other risk factors must precipitate ulcerationin certain persons with <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>infection,among them the level of acid and peptic activity, the nature of the hostinflammatory response, and cigarette smoking.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleNonsteroidal Antiinflammatory Drugs">Nonsteroidal AntiinflammatoryDrugs<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>NSAIDs produce a spectrum of injury to the gastroduodenalmucosa, from hemorrhages and petechiae to erosions and ulcers. The superficiallesions are of little clinical importance, except that they may provokeevaluation for occult gastrointestinal bleeding and may occasionally causechronic anemia. Many NSAIDs have topical irritative effects on the mucosa, andaspirin is the worst of the "barrier breakers." NSAIDs also have asystemic effect; parenteral aspirin, for example, produces ulcers but littlesuperficial mucosal damage. Similarly, pro-drugs, such as sulindac, and NSAIDsdelivered rectally or in enteric-coated capsules do not produce much acutesuperficial gastric damage,<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref18"style='border-style:initial;border-color:initial;border-image: initial;

outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>18</a><spanclass=apple-converted-space> but they may still cause chronic ulcers andlife-threatening ulcer complications.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref19"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>19</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'><o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Although NSAIDs have other potential actions, their ulcerogeniceffects are most likely attributable to the systemic inhibition ofprostaglandin production. Dramatic ulcer disease can be produced inexperimental models by antibodies to prostaglandins, but not by antibodies toinactive prostaglandin analogues.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref20"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>20</a><spanclass=apple-converted-space> Furthermore, NSAID-associated gastriculcers appear to be prevented more effectively by cotherapy with prostaglandinanalogues than by agents whose effects are only antisecretory.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref21"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>21</span

></a><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref22"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><spanstyle='font-size:8.5pt;color:#006892'>22</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref23"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>23</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'><o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>There is little doubt that the occurrence of ulcers increasesdramatically in patients taking NSAIDs. Recently, the Food and DrugAdministration warned about the risk of clinically relevant ulceration withNSAID treatment, which was estimated to be between 2 and 4 percent perpatient-year. This estimate was determined from the premarketing surveillanceof patients taking NSAIDs and is probably the most accurate estimate of thedrugs' gastrointestinal side effects; unfortunately, the data remainunpublished and unavailable for detailed review. Several epidemiologic studiesalso indicate that treatment with NSAIDs considerably increases the risk of theulcer complications of bleeding and perforation.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref24"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>24</a><spanclass=apple-converted-space> <

spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref25"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>25</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref26"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>26</a><spanclass=apple-converted-space> In a group of patients with rheumatoidarthritis, NSAID therapy was associated with a ninefold increase in the risk ofhospitalization for upper gastrointestinal ulcers and their complications.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref27"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>27</a><spanclass=apple-converted-space> Measuring the influence of a particularrisk factor on a disease is a challenging task; the process is limited bybiases inherent in the methods of detecting disease, selecting the study andcontrol groups, and controlling the quality of the data.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref28"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>28</a><spanclass=apple-converted-space> Although conflicting results have been

published, the weight of the evidence leaves little doubt that NSAIDs are aclinically relevant cause of ulcer complications, a precipitating factor, orboth.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Several factors appear to increase the risk of ulcers andcomplications in persons taking NSAIDs, including a history of peptic ulcerdisease,<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref23"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>23</a><spanclass=apple-converted-space> cigarette smoking, and a diagnosis ofalcohol-related disease.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref19"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>19</a><spanclass=apple-converted-space> Although gastroduodenal ulceration islikely to increase with the dose of NSAIDs, safe ranges cannot be identified.In fact, a recent hospital-based, controlled study indicated thatgastrointestinal bleeding due to aspirin therapy is dose-dependent, but thatrisk increases detectably at a daily dose of 325 mg (Kaufman DW, et al.:personal communication). The risk associated with the duration of NSAID therapyis uncertain. In one series, 25 percent of serious ulcer complicationsdeveloped after less than one month of NSAID therapy, and some complicationswere observed in the first week.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref29"style='border-style:initial;border-color:initial;border-image: initial;

outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>29</a><spanclass=apple-converted-space> Although hard data are limited, ulcercomplications can apparently occur after a few days or a few years of NSAIDtherapy. The incidence of complications attributable to NSAIDs is highest inelderly people, particularly elderly women, in part because this group consumesthe most NSAIDs.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref24"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>24</a><spanclass=apple-converted-space> The risk associated with ulcercomplications is also higher in elderly people; mortality in emergency ulcersurgery increases markedly above the age of 60. Preliminary studies in patientspresenting with gastric ulcer found gastritis and<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>colonizationin 90 percent (9 of 10) of the patients who were not taking NSAIDs, but in only42 percent (5 of 12) of those taking the drugs.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref30"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>30</a><spanclass=apple-converted-space> One can thus speculate that two types ofNSAID-associated ulcers exist: ulcers that occur de novo in histologicallynormal gastric mucosa, and ulcers that are due to the exacerbation by NSAIDs ofan underlying peptic diathesis — the latter presumably distinguished from theformer by the presence of antral gastritis and<spanclass=apple-converted-space> <em style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: ini

tial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>colonization.Studies are needed to establish whether patients with gastritis or<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> colonization are in fact more sensitive toNSAIDs and whether the incidence or severity of the ulceration associated withNSAIDs would be reduced by the eradication of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>beforetheir use.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Although acute injury caused by NSAIDs is more frequent in thestomach than the duodenum, ulcer complications associated with NSAIDs occurwith about equal frequency in these two sites.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref25"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>25</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<span

class=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref31"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>31</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Sincenon-NSAID peptic ulcer is more frequent in the duodenum than the stomach, it ispossible that many NSAID-associated complications reflect the exacerbation ofan underlying peptic diathesis. This distinction may be important whenconsidering prophylactic treatments.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleCigarette Smoking"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>CigaretteSmoking<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Controlled trials have provided solid evidence that cigarettesmoking impairs healing and promotes the recurrence of ulcers. Active therapyattenuates the effects of smoking, so smoking's most dramatic influence isfound in the patients given placebo.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref32"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>32</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref33"style='border-style:initial;border-color:initial;border-image: initial;

outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>33</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref34"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>34</a><spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref35"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>35</a><spanclass=apple-converted-space> Cigarette smoking also increases thelikelihood that surgery will be required and increases the risks of surgery.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref36"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>36</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Numerousmechanisms have been proposed to explain the effect of smoking on peptic ulcer,<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref37"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>37</a><span

style='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>includingthe stimulation of acid secretion,<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref38"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>38</a><spanclass=apple-converted-space> alteration of blood flow or motility,induction of bile reflux,<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref39"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>39</a><spanclass=apple-converted-space> and reduction in the generation ofprostaglandins.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref40"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>40</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <span

style='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref41"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>41</a><spanclass=apple-converted-space> The long list of possible mechanismssuggests either that the effects of smoking are multifactorial and vary fromperson to person or that the important variable has not been identified.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleOther Risk Factors"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>OtherRisk Factors<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Folklore implicates diet, caffeine, and psychological stress inthe pathogenesis of peptic ulcer, but studying such risk factors is difficult<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref28"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>28</a><spanclass=apple-converted-space> and supporting evidence is problematic.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> <span style='font-size:9.5pt;font-family:

"Arial","sans-serif";color:#333333'>Isolated case reports suggest anassociation between psychological stress and peptic disease, and controlledstudies indicate such an association,<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref42"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>42</a><spanclass=apple-converted-space> but the difficulty of measuring stress and,more important, assessing the response to stress has hampered the rigorousstudy of its role in the pathogenesis of peptic ulcer. The effect of alcohol onpeptic ulcer is controversial. The consumption of alcohol has been reportedboth to enhance<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref43"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>43</a><spanclass=apple-converted-space> and impair<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref35"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>35</a><spanclass=apple-converted-space> healing. Cirrhosis due to the consumptionof alcohol or to other causes is linked to an increased incidence of pepticulcer.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> Certain diseases, such as chronic pulmonarydisease, have also been associated with peptic ulcer.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> Genetic factors may also be important.Autosomal dominant inheritance of hyperpepsinogenemia I is common in duodenalulcer, but the nature of causal relations to the pathogenesis of ulcer remainsuncertain. Several rare genetic syndromes may also be associated with pepticulcer.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'><o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleSymptomatic and Silent Ulcers">SYMPTOMATICAND SILENT ULCERS<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Symptoms and ulcers are frequently dissociated.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><span style='font-size:10.0pt;

font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref44"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>44</a><spanclass=apple-converted-space> Acute silent ulcers can cause complicationsin persons with no history of chronic ulcers and no heralding symptoms. In onestudy, about 25 percent of the severe complications due to peptic ulcers notrelated to the use of NSAIDs presented in this fashion.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref29"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>29</a><spanclass=apple-converted-space> In persons taking NSAIDs, silentpresentation with complications appears to be even more frequent.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref29"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>29</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref44"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:

inherit;font-style:inherit'>44</a><spanclass=apple-converted-space> Silent ulcers are also more common inelderly patients with no history of peptic ulcer; whether this increase is dueto the use of NSAIDs or to a decrease in sensitivity to pain associated withage is not known. Persons with a history of ulcer disease who are not usinganti-ulcer therapy can also have silent ulcers that subsequently producesymptoms or complications.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref45"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>45</a><spanclass=apple-converted-space> Finally, silent "breakthrough"ulcers are commonly detected in patients who are undergoing maintenance therapy.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref45"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>45</a><span

class=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref46"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>46</a><spanclass=apple-converted-space> Breakthrough ulcers may result from poorcompliance with the maintenance regimen, but they can also occur whencompliance is good. In that case, breakthrough ulcers are often clinicallybenign and cause few complications or symptoms.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref45"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>45</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref46"

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>46</a><spanclass=apple-converted-space> It is therefore difficult to justifyaggressive measures to detect or treat such ulcers in the absence of symptomsor complications.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleTherapeutic Approaches to Peptic Ulcer">THERAPEUTICAPPROACHES TO PEPTIC ULCER<o:p></o:p></h3>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleInitial Healing"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>InitialHealing<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>In the past decade several therapies have been shown to enhancethe healing of peptic ulcers. They involve the inhibition of acid secretion,the neutralization of acid, and actions independent of acid, such as the"cytoprotective" actions associated with sucralfate and bismuth.Three classes of agents inhibit the secretion of acid by directly affectingparietal cells: antagonists for the histamine H2<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>andmuscarinic receptors, prostaglandins that inhibit adenylate cyclase through thereceptors linked to the inhibitory guanosine triphosphate—binding protein ofadenylate cyclase, and compounds such as omeprazole that inhibit thehydrogen—potassium adenosinetriphosphatase, the enzyme that drives acidsecretion. The mechanisms of action of these inhibitors have recently beenreviewed.<span style='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0

pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref5"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>5</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'><o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>The healing of ulcers is accelerated by a similar order ofmagnitude with all these therapies. The rapidity and efficacy of healingcorrelate to some extent, however, with antisecretory effectiveness.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref47"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>47</a><spanclass=apple-converted-space> Omeprazole, particularly at doses of morethan 20 mg a day, accelerates the early phase of ulcer healing, probablybecause of its marked antisecretory efficacy.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleTreatment of H. pylori Infection">Treatment of H. pyloriInfection<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>It has recently been recognized that bismuth compounds, whichhave been used for decades in treating peptic disorders, affect<spanclass=apple-converted-space> H. pylori<span

class=apple-converted-space> colonization and infection. Many factorsmake it difficult to determine the importance of<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> in peptic ulcer disease. First, killing theorganism in vitro does not predict drug efficacy in vivo.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref14"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>14</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref48"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>48</a><spanclass=apple-converted-space> Second, <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> </s

pan><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>isdifficult to eradicate; recurrent infections are frequent and generally occurwithin a few weeks.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref13"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>13</a><spanclass=apple-converted-space> They usually reflect incomplete eradicationof the initial infection rather than reinfection, since the strain that emergesis identical to the original infecting strain.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref49"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>49</a><spanclass=apple-converted-space> The continued absence of the organism sixweeks after the completion of therapy is usually predictive of negativecultures after one year.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> Effective eradication appears to requirecombination antibiotic therapy. Preliminary data indicate that a combination ofcolloidal bismuth and an antibiotic is most effective.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><a

href="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> Bismuth alone eradicates about 20 percentof the <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>aftersix weeks of therapy, and the antimicrobial agent tinidazole alone eradicatesabout 5 percent of the organisms, but the combination eradicates about 70percent.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> Many other combinations of antibiotics arebeing tested, but their relative efficacy has not been established. Resistanceto antibiotics often develops, and untoward side effects — including apseudomembranous diarrhea — are common with antibiotic regimens. Bismuth levelsin urine remain elevated for weeks after therapy.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref50"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>50</a><spanclass=apple-converted-space> Although toxicity has not been reportedduring the standard six-week course of therapy, caution must be exercised withprolonged use or repeated courses of bismuth.<span style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:

inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref51"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>51</a><spanclass=apple-converted-space> Bismuth compounds, in addition to affecting<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>, maycontribute to the healing of ulcers by other mechanisms, such as stimulatingthe production of prostaglandins, altering mucus, and modulating the immuneresponse.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>The influence of the patient's <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>statuson the course of ulcer disease remains to be established in controlled,randomized studies. Two studies support the tantalizing possibility that theclearance of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>has abeneficial effect on the natural history of peptic ulcer disease.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref52"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>52</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>However,these studies can be faulted for problems such as inadequate blinding, samplingfor <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>H.pylori, and randomization, their small number of patients, low overallinitial healing, and a definition of recurrence that included symptoms withoutthe documentation of ulceration. The patients were treated with bismuth,tinidazole, or cimetidine, alone or in combination; those with persistent<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> infection had a lower rate of ulcer healingor a higher rate of recurrence (or both) than those in whom<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> <span style='font-size:9.5pt;font-family:

"Arial","sans-serif";color:#333333'>was eliminated. However, ulcers did recurin some patients without persistent <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>infection.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref12"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>12</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref52"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>52</a><spanclass=apple-converted-space> Others have found in preliminary studiesthat rates of ulcer recurrence are unaffected by the presence or absence of<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:

inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref53"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>53</a><spanclass=apple-converted-space> In the light of the uncertainty thatsurroundsH. pylori, even enthusiasts agree that theeradication of the organism is not currently an appropriate goal of ulcertherapy. However, the outcome of ongoing controlled clinical trials testingvarious combinations of colloidal bismuth, antibiotics, and antisecretoryagents is likely to alter our future approach to ulcer disease.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id=articleProstaglandins><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Prostaglandins<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Synthetic prostaglandins, such as misoprostol, induce thehealing of ordinary peptic ulcer, but with an effectiveness no greater thanthat predicted by their antisecretory actions.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref54"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>54</a><spanclass=apple-converted-space> Thus, although prostaglandins enhancemechanisms thought to be involved in mucosal defense (e.g., the secretion ofmucus, output of bicarbonate, and blood flow), these effects do not seem to

benefit the healing of ordinary peptic ulcer. Chronic peptic ulcers aresurrounded by a rim of dense inflammation that disrupts and replaces normalmucosa. It is possible that the effects of prostaglandins on ordinary pepticulcer may not be dramatic because the targets for their enhancement of mucosaldefense (e.g., epithelial cells and normal mucosal blood vessels) are disruptedin the vicinity of the ulcer. The failure of replacement therapy withprostaglandins to benefit the healing or natural history of ordinary pepticulcers beyond its anticipated antisecretory effect argues that prostaglandindeficiency is not of primary pathogenic importance in this disease.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleRecurrence of Peptic Ulcer">Recurrence of Peptic Ulcer<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Peptic ulcers rapidly recur after the cessation of therapy;recurrence is suppressed by maintenance therapy with H<substyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit;bottom: -0.25em'>2<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>-receptorblockers.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> Evidence suggests that the rate ofrecurrence differs with different therapies and that the rate is lower afterbismuth therapy.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref55"style='border-style:initial;border-color:initial;border-image: initial;

outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>55</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref56"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>56</a><spanclass=apple-converted-space> As noted above, this reduction inrecurrence may reflect the effect of bismuth on<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> infection, but controlled studies will benecessary to establish this point.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id="articleRefractory Ulcers"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>RefractoryUlcers<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Regardless of the mode of therapy, the healing of ulcers istime-dependent; 90 to 95 percent of all ulcers heal if therapy is continued for

12 weeks. After that, ulcers or symptoms (or both) can be considered refractoryto therapy. Since persistent symptoms may not be due to persistent ulcerdisease, endoscopy is essential to establish the diagnosis. If persistentulceration is found on endoscopy, a few possibilities warrant consideration.Poor patient compliance is a common cause of refractory ulceration. The use ofNSAIDs and smoking may be contributing factors. Healing varies with ulcer size,and large ulcers require more time to heal.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref35"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>35</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref57"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>57</a><spanclass=apple-converted-space> Patients with gastrinoma represent anextreme case, in which an increase in the secretion of acid can lead to ulcersthat are refractory to conventional therapy. Some refractory ulcers appear toresult from the failure of conventional therapy to inhibit acid secretionadequately.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref58"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>58</a><span

class=apple-converted-space> The role of<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> infection in refractory ulceration alsoremains uncertain. One study suggested that ulcers that failed to heal afterfour weeks of cimetidine therapy responded better to bismuth than to continuedcimetidine,<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref59"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>59</a><spanclass=apple-converted-space> but the study was performed before data on<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> colonization were being collected.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Several treatment options are available for refractory ulcers,but none have been tested in controlled trials. An increase in antisecretoryefficacy and duration of action is likely to promote healing in many patientswith refractory ulcers. No benefit has been established for switching among theavailable H<span style='font-size:

7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>2<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>-receptorblockers at standard doses. Increasing the dose of an H<substyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit;bottom: -0.25em'>2<spanclass=apple-converted-space> blocker has been reported to promotehealing.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref58"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>58</a><spanclass=apple-converted-space> Although a single nighttime dose is aseffective as therapy twice a day for ordinary duodenal ulcer,<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref4"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>4</a><spanclass=apple-converted-space> the 24-hour suppression of acid secretionwith twice-daily therapy may be beneficial in refractory ulcers. A 40-mg dailydose of omeprazole, introduced for clinical use in the United States in October1989, provides the most promising treatment for refractory ulcers.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref8"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>8</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Full-doseantisecretory therapy will probably have to be continued to maintain the

healing of refractory ulcers, since it does not alter the natural history ofulcer disease. Treatment with bismuth or the eradication of<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> (or both) deserves consideration forpatients who do not respond to conventional therapy, although the efficacy ofthis treatment requires direct study, as does the optimal antibiotic regimen.Combination therapy (e.g., H<spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>2<spanclass=apple-converted-space> blockers plus sucralfate or H<substyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit;bottom: -0.25em'>2<spanclass=apple-converted-space> blockers plus anticholinergic agents) forrefractory ulcers is without established benefit.<o:p></o:p>

<h3 style='margin-top:3.0pt;margin-right:0in;margin-bottom:2.25pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'id="articleTherapy and Prevention of NSAID-Associated Ulcers"><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Therapyand Prevention of NSAID-Associated Ulcers<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Ulcers associated with NSAIDs usually heal rapidly when theNSAIDs are withdrawn. Even with the continued use of NSAIDs, ulcers may healspontaneously. Limited studies suggest that H<span style='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;

padding:0in'>2blockers, prostaglandins, and omeprazole accelerate healing ascompared with placebo.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref57"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>57</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref60"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>60</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>However,H2<spanclass=apple-converted-space> blockers may be less effective againstlarge gastric ulcers than small ones.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref60"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>60</a><span

style='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Furthermore,a controlled study has indicated that omeprazole may be superior to ranitidinein healing gastric ulcers in the face of continued NSAID therapy.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref57"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>57</a><spanclass=apple-converted-space> In that study, the continued consumption ofNSAIDs impaired healing in the patients treated with ranitidine but not inthose treated with 40 mg of omeprazole a day (<ahref="http://www.nejm.org/action/showImage?doi=10.1056%2FNEJM199003293221307&iid=f002"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Fig.2</a><spanclass=figuretitle>FIGURE 2<spanstyle='border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/action/showImage?doi=10.1056%2FNEJM199003293221307&iid=f002"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><![if !vml]><imgborder=0 width=111 height=75

src="faktorfaktor_risiko_yang_berhu_6450405056_files/image002.gif"alt="http://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/1990/nejm_1990.322.issue-13/nejm199003293221307/production/images/small/nejm199003293221307_f2.gif"v:shapes="Picture_x0020_4"><![endif]></a><spanclass=figurecaption>The Effects of Nonsteroidal Antiinflammatory Drugs (NSAIDs) on theHealing of Gastric Ulcer with Ranitidine and Omeprazole.<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>). Thenumbers of patients taking NSAIDs were small, and additional studies areneeded, but omeprazole is emerging as the most promising agent for troublesomeulcers, especially when NSAIDs cannot be discontinued.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A few trials have tested regimens for the prophylactic treatmentof NSAID-associated ulceration. One three-month trial indicated thatmisoprostol prevented NSAID-associated gastric ulcer, but data were notobtained on the efficacy of prostaglandins in preventing NSAID-associatedduodenal ulcer.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref22"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>22</a><spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>Incontrast, H2<spanclass=apple-converted-space> blockers do not prevent gastric ulcer butdo prevent NSAID-associated duodenal ulcer.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref23"style='border-style:initial;border-color:initial;border-image: initial;

outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>23</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref61"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>61</a><spanclass=apple-converted-space> A short-term study (one week of NSAIDtherapy) indicated that prostaglandins were more effective than H2 blockers inpreventing NSAID-induced acute gastric damage, whereas the agents were equallyeffective in preventing duodenal damage.<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref21"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>21</a><spanclass=apple-converted-space> Although sucralfate reduces superficialdamage from NSAIDs somewhat,<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref62"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>62</span

></a><spanclass=apple-converted-space> there are no published studies thatdemonstrate the prevention of ulceration. All the available studies ofprophylactic treatment are problematic, since lesions are endoscopically gradedby size, making it difficult to differentiate between ulcers that penetrate thesubmucosa and superficial erosions. Since these studies excluded chroniculcers, the lesions examined were acute and had less surrounding inflammationand fibrosis; their natural history and response to therapy probably differedfrom those of chronic ulcers. Screening by endoscopy provides a firstapproximate measure of therapeutic efficacy. If an agent does not prevent acuteNSAID-associated lesions, it is unlikely to prevent NSAID-associated complications.On the other hand, an agent is likely to prevent clinical ulcers and theircomplications if it effectively prevents acute lesions, especially lesionslarger than 5 mm in diameter, which are more likely to be ulcers. However, allcandidate therapies must be tested by properly designed studies of more thanthree months' duration, with appropriate clinical end points (bleeding,perforation, hospitalization, and so forth). It is also important to determinewhether intervention prevents the NSAID-induced exacerbation of underlyingpeptic disease as well as new NSAID-induced ulcers. Such data are needed todetermine whether the benefit of reduced complications justifies the costs andpotential risks of prolonged drug therapy. Identifying the risk factors forNSAID-associated ulcers is important in order to focus preventive therapy onthe persons who are at increased risk. However, the predictive value of any setof risk factors remains speculative. Thus, with regard to the prevention ofNSAID-associated ulcer complications, physicians are faced with the familiarproblem of making decisions with inadequate information. It is hoped that newstudies will soon throw light on these important unresolved questions.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit' id=articleDiscussion><spanstyle='font-size:10.5pt;font-family:"Arial","sans-serif";color:#333333;text-transform:uppercase'>DISCUSSION<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Raj Goyal: Is there any difference in the treatment ofgastric and duodenal ulcers?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: Probably not, except that gastric ulcers may heal moreslowly and need more sustained treatment. Ulcers that occur in the prepyloricregion of the antrum behave like typical duodenal ulcers. Ulcers that occur

more proximally are likely to be associated with more widespread gastritis andless acid secretion. Gastric ulcers may be less dependent on acid secretion,but the implication of that fact for therapeutic choices remains uncertain.<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> may be less closely associated with gastriculcers than duodenal ulcers, but ascertaining the pathogenic role of<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>ingastric as compared with duodenal ulcers awaits additional data. Of course, amajor difference is the necessity of confirming complete healing in gastriculcers to exclude the possibility of carcinoma underlying a gastric ulcerationthat appears benign.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A Physician: Why is it that misoprostol makes your stomach lookgood but makes you feel worse?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: You raise an important point that reflects thefrequent dissociation between symptoms and macroscopic gastric lesions inpersons taking NSAIDs. The effects of intervention on symptoms and lesions aresimilarly dissociated. A recent study<spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref22"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>22</a><spanclass=apple-converted-space><span style='font-size:9.5pt;font-family:"Arial","sans-serif";

color:#333333'> suggested that during three months oftherapy, 70 to 75 percent of the patients taking NSAIDs who enrolled withsymptoms and were treated with misoprostol became symptom-free, as comparedwith about 50 percent of the patients given placebo. This difference was notsignificant. Although H<spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>2<spanclass=apple-converted-space> blockers reportedly reduce NSAID-associateddyspepsia,<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref61"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>61</a><spanclass=apple-converted-space> <spanstyle='font-size:7.5pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'>,<spanclass=apple-converted-space> <spanstyle='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref63"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>63</a><spanclass=apple-converted-space> the magnitude of the differences, althoughsignificant, was similar to that reported for the prostaglandin study.<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><span style='font-size:10.0pt;

font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref22"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>22</a><spanclass=apple-converted-space> Thus, the effects of various therapies onNSAID-associated dyspepsia deserve comparative study. It is unclear whethermisoprostol makes the patients taking NSAIDs feel better or only theirendoscopist feel better. Although many patients tolerate misoprostol withoutuntoward effects, some patients, as you suggest, do feel worse when taking thedrug, largely because of diarrhea and cramps. These symptoms are usuallytransient and may respond to a reduction in dose to 100 μg four times a day.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A Physician: Could misoprostol just not be the idealprostaglandin? Is it possible that some of the newer ones will be associatedwith fewer side effects such as diarrhea?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: It is possible that other prostaglandin analogues willnot produce diarrhea or uterotropic side effects. The specificity of thereceptors that mediate the effects of prostaglandin differs subtly. Forexample, misoprostol and enprostil share the ability to inhibit theparietal-cell response to histamine, an effect mediated by the inhibition ofadenylate cyclase.<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref64"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>64</a><spanclass=apple-converted-space> In contrast, misoprostol, but notenprostil, stimulates adenylate cyclase in several types of mucosal cells.Whether the difference in the ability of prostaglandin analogues to alter

adenylate cyclase activity in different cell types translates into a differentspectrum of effects and side effects remains to be established.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A Physician: What is the optimal pH for the growth andreplication of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>adheresto mucus and is incredibly well adapted to the stomach. It produces urease inlarge amounts, which increases the pH in the micro-environment of the bacteria.Thus, <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>has aspecialization that allows it to survive in an acid environment.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. C. Ronald Kahn: With regard to the cause of ulcer, what isthe status of <em

style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>inpatients with gastrinoma who have primary acid hypersecretion?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: Patients with gastrinoma are generally free of<spanclass=apple-converted-space> H. pylori<spanclass=apple-converted-space> infection. This is one instance in whichpeptic ulcers occur in the absence of <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori. In 1978,<ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref65"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>65</a><spanclass=apple-converted-space> the case of a patient with theZollinger—Ellison syndrome was reported in which acute gastritis had developed,with subsequent remission of the ulcer disease. Retrospective analysis ofgastric biopsy specimens indicated the presence of<spanclass=apple-converted-space> <span style='font-size:10.0pt;font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;

mso-border-alt:none windowtext 0in;padding:0in'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Goyal: Do you have some practical advice about the role ofcombination therapy with acid suppression and the treatment of<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>? Shouldwe worry about treating <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: For an ordinary peptic ulcer that responds well toantisecretory therapy, I see no reason at present to treat for<spanclass=apple-converted-space> H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>,particularly since the appropriate regimen has not been defined. On the otherhand, for refractory ulcers that do not respond to antisecretory therapy, Iwould consider eradicating <emstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'> <spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>as oneof the primary options. Pepto-Bismol contains bismuth subsalicylate and appearsto be as effective as the other bismuth compounds in eradicating<spanclass=apple-converted-space> <em style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: ini

tial;outline-color: initial;font-weight:inherit'>H. pylori<spanstyle='font-size:9.5pt;font-family:"Arial","sans-serif";color:#333333'>,particularly in combination with metronidazole.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A Physician: Does the salicylate in Pepto-Bismol pose any riskto the gastric mucosa?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: I don't know whether subsalicylate can inhibitcyclooxygenase or whether it is absorbed when administered as a bismuth salt.Sodium salicylate has been found to be a less effective inhibitor ofprostaglandin production in the gastric mucosa than acetyl-salicylic acid(aspirin).<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>A Physician: Under what conditions should one be concerned abouthypergastrinemia in patients undergoing antisecretory therapy?<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:16.8pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Dr. Soll: Female rats treated with very-high-dose, lifelongantisecretory therapy have marked hypergastrinemia, and associated carcinoidtumors composed of enterochromaffin-like cells can develop. There is goodevidence that these endocrine tumors result from a trophic effect of profoundhypergastrinemia. In humans, hypergastrinemia is also produced bypharmacologically induced hypochlorhydria. However, in most persons the degreeof hypergastrinemia is slight, and hyperplasia of enterochromaffin-like cellshas not been observed. Marked hypergastrinemia develops in less than 10 percentof subjects who are taking potent, long-acting antisecretory agents,<spanstyle='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'><span style='font-size:10.0pt;

font-family:"Arial","sans-serif";color:#333333;border:none windowtext 1.0pt;mso-border-alt:none windowtext 0in;padding:0in'><ahref="http://www.nejm.org/doi/full/10.1056/NEJM199003293221307#ref66"style='border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>66</a><spanclass=apple-converted-space> and it is these patients, if any, who maybe at risk for hyperplasia of enterochromaffin-like cells. While we awaitproper data to guide us, we can probably identify the patients undergoingprolonged antisecretory therapy who may be at risk by measuring fasting andpostprandial serum gastrin levels. I would proceed with a gastric biopsy andconsultation with an endocrine-cell pathologist if gastrin levels are elevatedseveral-fold.<o:p></o:p>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:11.25pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>Supported in part by the Medical Research Service of theDepartment of Veterans Affairs and by grants (DK 19984 and DK 30444) from theNational Institute of Diabetes and Digestive and Kidney Diseases.<o:p></o:p>

<h3 style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:.5in;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-style:inherit'>SOURCEINFORMATION<o:p></o:p></h3>

<p style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:.5in;margin-bottom:.0001pt;line-height:11.25pt;background:white;vertical-align:baseline;border-style:initial;border-color:initial;border-image: initial;outline-width: 0px;outline-style: initial;outline-color: initial;font-weight:inherit;font-style:inherit'>From the UCLA School of Medicine and the Wadsworth VeteransAffairs Hospital Center, Los Angeles. Address reprint requests to Dr. Soll atthe Center for Ulcer Research and Education, Bldg. 115, Rm. 203, WadsworthVeterans Affairs Hospital Center, Los Angeles, CA 90073.<o:p></o:p>

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