This document provides information on peptic ulcer disease (PUD), including its definition, causes, risk factors, pathophysiology, clinical presentation, diagnosis, and treatment. The main points are: 1. PUD is caused by an imbalance between gastric acid/pepsin and mucosal defenses, and is commonly due to H. pylori infection or NSAID use. 2. Risk factors include smoking, alcohol, stress, and certain diseases. 3. H. pylori and NSAIDs cause ulcers by different mechanisms that impair the mucosal barrier. 4. Diagnosis involves endoscopy, biopsy, and non-invasive tests like the urea breath test to detect

1. Salahadin A. (B.Pharm.)
School of Pharmacy
Haramaya University
Ethiopia.
Peptic Ulcer Disease

2. DEFINITION
 Peptic ulcer disease (PUD) refers to a group of
ulcerative disorders of the upper GI tract that require
acid and pepsin for their formation.
 Ulcers differ from gastritis and erosions in that they
extend deeper into the muscularis mucosa.
 The three common forms of peptic ulcers include
Helicobacter pylori (HP)–associated ulcers,
nonsteroidal antiinflammatory drug (NSAID)–induced
ulcers, and
stress-related mucosal damage (also called stress

3.  Chronic peptic ulcers are
 defects in the gastric (gastric ulcer) or
 duodenal (duodenal ulcer) mucosa that
require gastric acid for their formation.
 Stress ulcer is an acute form of peptic ulcer,
but it occurs primarily in critically ill patients and
differs in its underlying pathogenesis

4. Comparing Duodenal
and Gastric Ulcers

5. Duodenal Ulcers
 duodenal sites are 4x as common as gastric sites
 most common in middle age
 peak 30-50 years
 Male to female ratio—4:1
 Genetic link: 3x more common in 1st degree relatives
 more common in patients with blood group O
 associated with increased serum pepsinogen
 H. pylori infection common
 up to 95%
 smoking is twice as common

6. Gastric Ulcers
 common in late middle age
 incidence increases with age
 Male to female ratio—2:1
 More common in patients with blood group A
 Use of NSAIDs - associated with a three- to four-fold
increase in risk of gastric ulcer
 Less related to H. pylori than duodenal ulcers – about
80%
 10 - 20% of patients with a gastric ulcer have a
concomitant duodenal ulcer

7. Epidemiology
 PUD develops in 10% of Americans during
their lifetime and result in
impaired quality of life,
work loss, and
high-cost medical care.
 A declining ulcer rate for younger men and
an increasing rate for older women.

8. Etiology and Risk Factors
 H. pylori and NSAIDs
 are the two most common causes of chronic
PUD and influence the chronicity of the disease.
 Less common causes include
 hypersecretory states such as Zollinger-Ellison
syndrome (ZES),
 viral infections (e.g., cytomegalovirus),
radiation, and

9. Factors that may increase the risk of
PUD
 alcohol ingestion,
 cigarette smoking,
 diet,
 psychologic stress;
 corticosteroids; and
 chronic diseases such as chronic renal failure,
hepatic cirrhosis, chronic pancreatitis, chronic
pulmonary disease, and Crohn's disease.

10. Helicobacter pylori–Related Ulcers
 H. pylori infection is causally linked to chronic gastritis
(90%), PUD (95-100%), mucosa-associated lymphoid
tissue (MALT) lymphoma, and gastric cancer, but only
20% of infected individuals develop symptomatic ulcers
and <1% develop gastric cancer.
 Differences in strains account for the variable
pathogenesis of the organism.
 Evidence is lacking to support a causal role for H. pylori
and GERD, extragastric manifestations (e.g.,
cardiovascular disease),or iron deficiency anemia

11.  The prevalence of H. pylori varies by
 geographic location,
 socioeconomic environment,
 ethnicity, and
 age.
 The infection is more common in developing
countries than in industrialized countries.
 The higher prevalence among older individuals
reflects acquisition during infancy and early
childhood.

12.  H. pylori Transmission occurs by the
 fecal–oral route from an infected person or
 from fecal-contaminated water or food.
 through vomitus or the use of inadequately
sterilized endoscopes
 Individuals living in the same household are at
risk for infection.
 infection rates in the United States have been
declining in children because of improved

13. NSAIDs-Induced Ulcers
 There is considerable evidence linking the chronic
use of NSAIDs with injury to the GI tract.
 Gastric and duodenal ulcers develop in 15%-30% of
chronic NSAID users, whereas 1%-2% experience
serious ulcer-related complications
 Gastric ulcer is most common and develops primarily
in the antrum.
 NSAIDs may cause ulcers in the esophagus and
the colon, but these ulcers occur less frequently.

14. Pathophysiology
 A physiological balance exists in healthy
individuals between gastric acid secretion and
gastroduodenal mucosal defense.
 Peptic ulcers occur when the balance between
aggressive factors (gastric acid, pepsin, bile
salts, H. pylori, and NSAIDs) and mucosal
defensive mechanisms (mucosal blood flow,
mucus, mucosal bicarbonate secretion, mucosal
cell restitution, and epithelial cell renewal) are

15. Protective factors vs. hostile factors

16.  Pepsin is an important cofactor that plays a
role in the proteolytic activity involved in
ulcer formation.
 Mucosal defense and repair mechanisms
protect the gastroduodenal mucosa from
noxious endogenous and exogenous
substances.
 The viscous nature and near-neutral pH of
the mucus-bicarbonate barrier protect the

17.  The maintenance of mucosal integrity and
repair is mediated by the production of
endogenous prostaglandins.
 When aggressive factors alter mucosal defense
mechanisms, back diffusion of hydrogen ions
occurs with subsequent mucosal injury.
 H. pylori and NSAIDs cause alterations in
mucosal defense by different mechanisms and
are important factors in the formation of peptic
ulcers.

18. Risk Factors for NSAIDs-Induced Ulcer
and Ulcer-Related Upper Gastrointestinal
Complications
 Established
 Confirmed prior ulcer or ulcer-related complication
 Age >65 years
 Multiple or high-dose NSAID use
 Concomitant use of aspirin (including cardioprotective
dosages)
 Concomitant use of an anticoagulant, corticosteroid,
bisphosphonate, clopidogrel, or SSRI
 Selection of NSAID (selectivity of COX-1 vs. COX-2)

19.  Nonselective NSAIDs, including aspirin, cause
peptic ulcers and upper GI complications by
systemically inhibiting protective prostaglandins
in the gastric mucosa.
 NSAIDs inhibit cyclo-oxygenase (COX), the rate-
limiting enzyme in the conversion of arachidonic
acid to prostaglandins.
 There are two COX isoforms: COX-1, which is
found in the stomach, kidney, intestine, and
platelets, and COX-2, which is induced with acute

20.  The inhibition of COX-1 is associated with upper
GI and renal toxicity, while the inhibition of COX-2
is related to anti-inflammatory effects.
 Nonselective NSAIDs, including aspirin, inhibit
both COX-1 and COX-2 to varying degrees and
decrease platelet aggregation, which may
increase the risk for upper GI bleeding.
 The partially selective NSAIDs may be associated
with less GI toxicity.

21.  Selective COX-2 inhibitors have a similar efficacy
to the nonselective NSAIDs but with fewer
harmful GI effects.
 In contrast to the nonselective NSAIDs, the COX-
2 inhibitors do not possess antiplatelet effects.
 Two selective COX-2 inhibitors, rofecoxib and
valdecoxib, were withdrawn from the U.S.
market in 2004 because of concerns about
cardiovascular safety.
 Celecoxib, a NSAID initially marketed as a COX-

22.  Aspirin and nonselective NSAIDs also have a
topical (direct) irritating effect on the gastric
mucosa, but the resulting inflammation and
erosion usually heals within a few days.
 Formulations such as enteric-coated aspirin,
buffered aspirin, NSAID prodrugs, and
parenteral or rectal preparations may spare
topical effects on the gastric mucosa,
 but all have the potential to cause a gastric
ulcer because of their systemic inhibition

23.  Selected Nonsteroidal Anti-inflammatory Drugs
 Salicylates
 Acetylated: aspirin
 Nonacetylated: trisalicylate, salsalate
 Nonsalicylates
 Nonselective (traditional) NSAIDs: ibuprofen, naproxen,
tolmetin, fenoprofen, sulindac, indomethacin, ketoprofen,
ketorolac, flurbiprofen, piroxicam
 Partially selective NSAIDs: etodolac, diclofenac,
meloxicam, nabumetone
 Selective COX-2 inhibitors: celecoxib, rofecoxib,
valdecoxib

24. Helicobacter pylori–Related Ulcers
 H. pylori is a gram-negative, spiral-shaped
bacillus that thrives in a microaerophilic
environment.
 The bacterium resides between the mucus layer
and surface epithelial cells in the stomach or
any location where gastric-type epithelium is
found.
 Flagella enable it to move from the lumen of the
stomach, where the pH is low, to the mucus

25. Helicobacter pylori:

26.  Although the exact method by which H. pylori induces
hypochlorhydria is uncertain, it is hypothesized that
its urease-producing ability hydrolyzes urea in the
gastric juice and converts it to ammonia and
carbon dioxide, which creates a neutral
microenvironment that surrounds the bacterium.
 Adherence pedestals permit the bacterium to attach
to gastric-type epithelium and prevent it from being
shed during cell turnover and mucus secretion.
 Colonization of the body of the stomach is associated

27.  Duodenal ulcers are thought to arise from
colonization by antral organisms of gastric-type
epithelium that develops in the duodenum in
response to changes in duodenal pH.
 The exact mechanism by which H. pylori
infection leads to ulceration is not yet
known.
 Direct mucosal damage is produced by
virulence factors (e.g., vacuolating cytotoxin,

28.  Approximately 50% of H. pylori strains produce
vacuolating cytotoxin (VacA), which leads to cell
death and possibly gastric cancer.
 Strains with cytotoxin-associated gene (CagA)
protein are associated with duodenal ulcer,
atrophic gastritis, and gastric cancer.
 H. pylori infection also causes alterations in the
host immune response, hypergastrinemia leading
to increased acid secretion, and carcinogenic
conversion of susceptible gastric epithelial cells.

29. Clinical Presentation
 Signs and Symptoms
 The signs and symptoms associated with a peptic ulcer
range from mild epigastric pain to life-threatening upper
GI complications.
 A change in the character of the pain may indicate an
ulcer-related complication.
 The absence of epigastric pain, especially in the elderly
who are taking NSAIDs, does not exclude the presence
of an ulcer or related complications.
 There is no one sign or symptom that differentiates a H.

30. Clinical Assessment and Diagnosis
 Tests for Detecting Helicobacter pylori
 The detection of H. pylori infection can be made by using
gastric mucosal biopsies in patients undergoing upper
endoscopy or by nonendoscopic tests.
 The selection of a specific method is influenced by the
clinical circumstance and the availability and cost of the
individual test.
 The endoscopic tests require a mucosal biopsy for the
rapid urease test, histology, or culture.
 Medications that reduce urease activity or the density of
H. pylori may decrease the sensitivity of the rapid urease
test by up to 25%.

31.  When possible, antibiotics and bismuth salts
should be withheld for 4 weeks and H2RAs and
PPIs for 1 to 2 weeks prior to endoscopic testing.
 Patients who are taking these medications at
endoscopy will require histology in addition to the
rapid urease test.
 Two biopsies are taken from different areas of the
stomach because patchy distribution of H. pylori can
result in false-negative results.
 Acute ulcer bleeding at the time of testing is likely
to decrease the sensitivity of the rapid urease test and

32. Diagnostic Tests for H.pylori
Infection
 Tests Utilizing Gastric Mucosal Biopsy in Patients
Undergoing Endoscopy
1. Rapid Urease Test
 Tests for active H. pylori infection; >90% sensitivity and
>95% specificity.
 In the presence of H.pylori urease, urea is metabolized to
ammonia and bicarbonate resulting in an increase in pH,
which changes the color of a pH-sensitive indicator.
 Results are rapid (usually within a few hours), and test is
less expensive than histology or culture.

33. 2. Histology
 Considered “gold standard” for detection of H. pylori
infection; >95% sensitivity and >95% specificity.
 Permits further histologic analysis and evaluation of
infected tissue (e.g., gastritis, ulceration,
adenocarcinoma); tests for active H. pylori infection.
 Results are not immediate; not recommended for
intitial diagnosis; more expensive than rapid
urease test.

34. 3. Culture
 Permits sensitivity testing to determine
antibiotic choice or resistance; 100% specific.
 Use usually limited to patients who fail several
courses of eradication therapy; tests for active
H. pylori infection.
 Results are not immediate; not recommended
for initial diagnosis; more expensive than
rapid urease test.

35. Tests That do not Utilize Gastric Mucosal Biopsy
non-endoscopic tests
 Tests for active H. pylori infection; >95% sensitivity
and >95% specificity.
 Radiolabeled urea with either C13 or C14 is given
orally; urease secreted by H. pylori in the stomach (if
present) hydrolyzes radiolabed urea to produce
radiolabled CO2, which is exhaled and then
quantified from the expired breath; radiation
exposure is minimal.
 Used to detect H. pylori prior to treatment and to
document posttreatment eradicaton.
 Results usually take about 2 days; less expensive
than tests that utilize gastric mucosal biopsy but
more expensive than serologic tests.
Urea Breath Test

36. Urease Breath Test.

37. Serologic Antibody Tests
 Detects IgG antibodies to H. pylori in serum, whole
blood or urine; quantitative seriologic tests have a
sensitivity of about 85% and specificity of about 79%.
 Qualitative in office tests; provide results quickly (usually
within 15 minutes) but yield more variable results.
 Tests are widely available and inexpensive.
 Not of benefit in documenting eradication, because
antibodies to H. pylori remain positive for years following
successful eradication of the infection.
 Results not affected by H2RAs, PPIs, antibiotics, or
bismuth unlike for the other tests.

38. Fecal Antigen Test
 Identifies H. pylori antigen in stool; sensitivity
and specificity comparable to the UBT for initial
diagnosis.
 H2RAs, PPIs, antibiotics, and bismuth may
cause false-negative results but to a lesser
extent than the UBT.
 Considered an alterative to detecting H.
pylori prior to treatment and documenting
post treatment eradicaton.

39.  The fecal antigen test is less expensive and
easier to perform than the UBT and may be
useful in children.
 Although comparable to the UBT in the
initial detection of H. pylori, the fecal
antigen test may be less accurate when
used to document eradication post
treatment.
 Salivary and urine antibody tests are under
investigation.

40. Laboratory Tests, Radiography &
endoscopy
 Generally, laboratory tests are not helpful in
the diagnosis of PUD.
 Fasting serum gastrin concentrations are only
recommended for patients unresponsive to
therapy or those suspected of having a
hypersecretory disease.
 Serum hematocrit (Hct) and hemoglobin
(Hgb) and stool hemoccult tests assist in the

41.  Acid secretion is expressed as basal acid output
(BAO), in response to a meal (meal-stimulated acid
secretion), or as maximal acid output (MAO).
 The BAO, meal-stimulated acid secretion, and MAO
varies according to age, gender, health, and time of
day.
 The BAO follows a circadian rhythm, with the
highest acid secretion occurring at night and the
lowest in the morning.
 An increase in the BAO:MAO ratio suggests a basal

42.  Confirmation of a peptic ulcer requires
visualizing the ulcer either by GI radiography or
upper endoscopy.
 Radiography
 is often the initial diagnostic procedure because
is less expensive than endoscopy and more
widely available.
 Double-contrast radiography is preferred
because it detects 60% to 80% of ulcers,

43.  Fiberoptic upper endoscopy
(esophagogastroduodenoscopy [EGD]) is the
gold standard, as it detects >90% of peptic
ulcers and permits direct inspection, biopsy,
visualization of superficial erosions, and sites of
active bleeding.
 Upper endoscopy is preferred if complications
are suspected or if an accurate diagnosis is
required.
 If a gastric ulcer is found on radiography,

44. Clinical Course and Prognosis
 The clinical course of PUD is characterized by
periods of exacerbations and remissions unless
the underlying cause is removed.
 Eradication of H. pylori decreases ulcer
recurrence and complications.
 Prophylactic cotherapy or the use of a selective COX-
2 inhibitor decreases the risk for ulcers and related
complications in high-risk patients taking NSAIDs

45.  It is estimated that about 20% of patients
with chronic PUD experience ulcer-related
complications.
 Mortality is highest in patients with gastric
ulcer.
 Adenocarcinoma in H. pylori-infected
patients occurs over 20 to 40 years and is
associated with a lifetime risk <1%.

46.  Complications
 The most serious life-threatening complications
associated with chronic PUD are
 upper GI bleeding (10%–15%),
 perforation into the abdominal cavity (7%), and
 gastric obstruction (2%).
 The incidence of ulcer-related upper GI bleeding and
perforation is increased in older patients taking
NSAIDs.
 The bleeding may be occult (hidden), present as
melena (black-colored stools), or hematemesis

47.  Mortality is high in patients who continue to bleed or
who rebleed and in patients with a perforated ulcer.
 The pain associated with perforation is typically
sudden, sharp, and severe, beginning initially in the
epigastric area but quickly spreading throughout the
upper abdominal area.
 Gastric outlet obstruction is caused by previous
ulcer healing and then scarring or edema of the
pylorus or duodenal bulb and can lead to symptoms
of gastric retention, including
 early satiety, bloating, anorexia, nausea, vomiting, and

48. Treatment
 Therapeutic Goals
 The therapeutic goals for treating PUD depend
on
 whether the ulcer is related to H. pylori or
associated with a NSAID.
 Treatment goals may differ depending on
 whether the ulcer is initial or recurrent and
 whether complications have occurred.

49.  Treatment is aimed at
relieving ulcer symptoms,
healing the ulcer,
preventing ulcer recurrence, and
reducing ulcer-related complications.
 When possible,
the most cost-effective drug regimen
should be utilized.

50. Nonpharmacologic Therapy
 Patients with PUD should discontinue NSAIDs
(including aspirin) if possible.
 Patients unable to tolerate certain foods and
beverages (e.g., spicy foods, caffeine, and
alcohol) may benefit from dietary
modifications.
 Lifestyle modifications including reducing
stress and decreasing or stopping cigarette

51.  Probiotics containing strains of Lactobacillus and
Bifidobacterium and foodstuffs (e.g., cranberry
juice and some milk proteins) with bioactive
components have been studied in at-risk individuals
to proactively control colonization of H. pylori.
 Patients with ulcer-related complications may
require surgery for bleeding, perforation, or
obstruction.
 However, patients may present with postoperative
consequences (e.g., postvagotomy diarrhea, dumping
syndrome, anemia) associated with these procedures.

52. Pharmacotherapy
 First-line therapy should be initiated with a PPI-
based three-drug regimen.
 If a second course of treatment is required, the PPI-
based three-drug regimen should contain different
antibiotics or a four-drug regimen with a bismuth salt,
metronidazole, tetracycline, and a PPI should be
used.
 Successful treatment will heal the ulcer and
eradicate the infection (cure the disease).

53.  Treatment of H. pylori–positive patients with a
conventional antiulcer drug is not recommended
because of the high rate of ulcer recurrence and
complications.
 Combining a PPI and H2RA or sucralfate and either a
H2RA or PPI is not recommended, because it adds to
drug costs without improving efficacy.
 Maintenance therapy with a PPI or H2RA should only be
necessary in high-risk patients with a history of ulcer
complications, those with H. pylori–negative ulcers, and
patients with other concomitant acid-related diseases

54.  Patients with NSAID-induced ulcers should be
tested to determine their H. pylori status.
 H. pylori–positive patients should be initially
treated with a PPI-based three-drug
eradication regimen.
 If the patient is H. pylori–negative, the NSAID
should be discontinued and treatment should
be initiated with antiulcer medications
 The duration of treatment should be extended
if the NSAID is continued.

55.  Prophylactic cotherapy with a PPI or
misoprostol or switching to an NSAID with
greater COX-2 selectivity is recommended
for patients at risk of developing ulcer-
related upper GI complications.

56. Drug Regimen Dose Frequency Duration
Proton Pump Inhibitor–Based Three-Drug Regimens
PPI Standard dose BIDa 10–14 daysb
Clarithromycin 500 mg BID 10–14 daysb
Amoxicillinc 1 g BID 10–14 daysb
or
PPI Standard dosea BIDa 10–14 daysb
Clarithromycin 500 mg BID 10–14 daysb
Metronidazolec 500 mg BID 10–14 daysb

57. Bismuth-Based Four-Drug Regimens
Bismuth subsalicylate 525 mg QID 10–14
days
Metronidazole 250–500 mg QID 10–14
days
Tetracycline plus 500 mg QID 10–14
days
PPI Standard dosea QD or
BIDa
10–14
days
or
H2RA Standard dosee BIDe 4–6 wks

58. Sequential Therapyf
PPI Standard dosea BIDa
Amoxicillin 1 g BID
Clarithromycin 250–500 mg BID
Metronidazole 250–500 mg BID

59. Salvage or Rescue Therapy
Bismuth subsalicylated 525 mg QID 10–14 days
Metronidazole 250–500 mg QID 10–14 days
Tetracycline 500 mg QID 10–14 days
PPI Standard dosea QD or BIDa 10–14 days
or
PPI Standard dosea BIDa 10–14 days
Amoxicillin 1 g BID 10–14 days
Levofloxacin 500 mg QD 10–14 days

60.  aOmeprazole 20 mg BID; lansoprazole 30 mg BID;
pantoprazole 40 mg BID; rabeprazole 20 mg BID or QD;
esomeprazole 20 mg BID or 40 mg QD.
 bAlthough 7-day regimens provide acceptable eradication
rates, the preferred treatment duration in the United
States is 10 to 14 days.
 cUse amoxicillin in nonpenicillin-allergic individuals;
substitute metronidazole for amoxicillin in penicillin-
allergic patients.
 dPylera, a prepackaged H. pylori regimen, contains
bismuth subcitrate potassium (biskalcitrate) 140 mg as
the bismuth salt in place of bismuth subsalicylate,
metronidazole 125 mg and tetracycline 125 mg per
capsule. The patient is directed to take three
capsules/dose with each meal and at bedtime. A
standard dose of a PPI is added to the regimen and
taken twice daily. All medications are taken for a 10-day

61. Cyclo-oxygenase-2 Inhibitors and
Cardiovascular Toxicity
 The risk for cardiovascular events in patients taking
COX-2 inhibitors increases with a number of factors,
including increased COX-2 selectivity, higher
dosages, a longer duration of treatment, and
preexisting cardiovascular risk.
 Although ulcers and ulcer-related complications were
less likely with rofecoxib than with naproxen in the
VIGOR trial, there was an increased number of
myocardial infarctions and thrombotic strokes
observed with rofecoxib.
 Similar cardiothrombolic events were observed in
other rofecoxib studies of longer duration. In 2004,
rofecoxib was withdrawn from the U.S. market. Soon

62.  The cardiovascular safety of celecoxib has also
been evaluated, but the risk of myocardial infarction
and thrombotic stroke is less certain.
 Although there appeared to be no difference in
cardiovascular risk when celecoxib was compared
with diclofenac and ibuprofen in the CLASS trial, a
dose-related increase was reported in one large
trial.
 Celecoxib remains available in the United States, but
cardiovascular risk must be evaluated in each patient
when considering the use of this drug.
 The lowest effective dose should always be used for
the shortest duration of time.
 There is increasing evidence that certain non- and
partially selective NSAIDs (e.g., ibuprofen,
diclofenac, and meloxicam) may also increase the
risk of myocardial infarction and thrombotic stroke.

63.  The American Heart Association has published
recommendations for NSAID use in persons with
confirmed cardiovascular disease or risk factors.
 Recommendations include initiating short-term
treatment with less risky options such as
acetaminophen or aspirin, tramadol, or
narcotics.
 The preferred nonselective NSAID is naproxen,
because it does not appear to increase
cardiovascular risk.
 NSAIDs with increasing COX-2 selectivity may be
tried if symptoms are not relieved.
 However, selective COX-2 inhibitors should be
reserved for those patients in whom there are no other
alternatives and should be used in the lowest effective
dose for the shortest period of time.
 Thus, GI safety of NSAIDs and selective COX-2

64. Evaluation/Follow-up/Referrals
 H. Pylori Positive: retesting for tx efficacy
 Urea breath test—no sooner than 4 weeks after therapy to avoid
false negative results
 Stool antigen test—an 8 week interval must be allowed after
therapy.
 H. Pylori Negative: evaluate symptoms after one
month. Patients who are controlled should cont. 2-4
more weeks.
 If symptoms persist then refer to specialist for
additional diagnostic testing.

65. References (1)
1. Marie A. Chisholm-Burns.Pharmacotherapy
Principles & Practice. Chisholm-burns Ma,
editor: The McGraw-Hill Companies, Inc. ; 2008.
2. Joseph T. DiPiro P, Executive Dean and
Professor, South Carolina College of
Pharmacy, University of South Carolina.
Pharmacotherapy A Pathophysiologic
Approach. Seventh Edition ed.: McGraw-Hill;
2008.
3. Koda-Kimble MAY, Lloyd Yee. Applied
Therapeutics: The Clinical Use Of Drugs, 9th
Edition. Koda-Kimble MAY, Lloyd Yee, editor:
Copyright ©2009 Lippincott Williams &

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www.microbewiki.kenyon.edu/index.php/Helicobacter
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