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DOI: 10.1542/pir.22-10-3492001;22;349Pediatrics in Review

Gisela Chelimsky and Steven CzinnPeptic Ulcer Disease in Children

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Peptic Ulcer Disease in ChildrenGisela Chelimsky, MD,*and Steven Czinn, MD Objectives After completing this article, readers should be able to:

1. Describe the different mechanisms involved in the pathogenesis of peptic ulcer disease.

2. Recognize the presenting symptoms of peptic ulcer disease and the differential diagno-

sis of those symptoms in children.

3. Clarify the role of endoscopic procedures in pediatric peptic ulcer disease.

4. Describe the role ofHelicobacter pylori in the pathogenesis of peptic ulcer disease.

5. Review the medications and dosages commonly used in the treatment of peptic ulcer

disease and H pylori infection in children.

IntroductionDuring the past decade, it has been estimated that peptic ulcer disease has affected more

than 4 million people in the United States annually. For much of the last century, the

pathogenesis of this disease was believed to be due to a number of predisposing factors, the

most important of which was the hypersecretion of gastric acid. The development of

pediatric flexible fiberoptic endoscopes that allowed the gastroenterologist to obtain

gastric biopsies and identification of the microorganism Helicobacter pylorihave changed

our understanding of gastritis in children.

PathogenesisAcid-peptic inflammation is believed to occur when there is an imbalance between

cytotoxic and cytoprotective factors in the upper gastrointestinal tract. The toxic mecha-

nisms include acid, pepsin, medications such as aspirin and nonsteroidal anti-inflammatory

drugs, bile acids, and infection with H pylori. The defensive or cytoprotective mechanisms

include the mucous layer, local bicarbonate secretion, and mucosal blood flow.

Acid secretion from the parietal cells can be stimulated by three secretagogues:

histamine via the paraendocrine pathway, acetylcholine via the neuroendocrine pathway,

and gastrin via the endocrine pathway. Each employs a different mode of delivery to its

target, the oxyntic cell. Acethylcholine is released at the vagal cholinergic terminals near

the oxyntic cells (or parietal cell). Gastrin is released by the G cells in the antral and

duodenal mucosa and is carried by the blood to the oxyntic cells. Histamine is released by

mast-like cells of the lamina propria of the oxyntic (acid-secreting) mucosa into the

extracellular fluid, through which it diffuses to the adjacent oxyntic cells. The final

common pathway for all acid secretion within the parietal cell is the proton pump (H/K

ATPase). With each proton (H) secreted into the gastric lumen by the proton pump, a

chloride ion also is secreted. The secretion of pepsin, enzymes that hydrolyze proteins, alsois stimulated by factors that promote gastric acid secretion. The precursor of pepsin,

pepsinogen, is secreted by the chief cells and is converted to the active form at an acidic pH

(5). Finally, medications such as nonsteroidal anti-inflammatory drugs and acetazol-

amide inhibit the bicarbonate secretion.

The primary mechanism by which the host prevents the development of peptic ulcer

disease is secretion of mucus by superficial epithelial cells and mucus cells from glands

throughout the stomach. The thick mucous layer retards the diffusion of acid from the

lumen to the gastric mucosal surface, thereby protecting the gastric epithelium. In addition

*Department of Pediatrics.Chief, Division of Pediatric Gastroenterology, Department of Pediatrics, Rainbow Babies and Childrens Hospital and Case

Western Reserve University, Cleveland, OH.

Article gastroenterology

Pediatrics in Review Vol.22 No.10 October 2001 349

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to secretion of mucus, protection is increased by the

secretion of bicarbonate, which produces a pH gradient,with decreasing acidity on the epithelial side that mini-

mizes the deleterious effect of the low pH. The stomach

and duodenum produce bicarbonate. The mechanisms

involved in bicarbonate secretion include vagal-mediated

stimulation as well as HCO3 secretion stimulated by

acid in the lumen, both in the stomach and duodenum.

Clinical PresentationRecurrent epigastric abdominal pain is the hallmark

symptom of acid-peptic disease, and in many cases, there

is a family history of peptic ulcer disease. Other associatedbut less specific symptoms include nocturnal pain that

awakens the child from sleep, postprandial pain, oral

regurgitation, and vomiting. Less frequently, the child

may present with upper gastrointestinal bleeding, occult

blood in the feces, and weight loss. Finally, although

primarily associated with functional abdominal pain,

periumbilical abdominal pain, when seen with other

symptoms, may be a presentation of peptic ulcer disease.

Unfortunately, the symptoms described previously may

not indicate a specific etiology of acid-peptic disease; they

also can result from other medical conditions such as

parasitic infections, pancreatitis, Crohn disease, biliary/hepatic disease, lactose intolerance, or H pyloriinfection.

In this era of medical cost containment, it is critical to

develop a systematic approach for the evaluation of a

child who has recurrent abdominal pain that can discrim-

inate between functional and organic etiologies. Dyspep-

sia is a syndrome of nonspecific symptoms related to the

upper gastrointestinal tract that are intermittent or con-

tinuous for at least 2 months duration. We have devel-

oped major and minor criteria that we believe will help

the physician determine which child who has symptoms

of dyspepsia should undergo further evaluation (manu-

script in preparation). Two major and nine minor clinical

criteria have been identified (Table 1). A child who has

abdominal pain must have a constellation of signs or

symptoms that includes either both major criteria, one

major and two minor criteria, or four minor criteria to

justify an extensive medical evaluation and possible refer-

ral to a pediatric gastroenterologist for identification of

an organic etiology. A child who has met the criteria for

the diagnosis of dyspepsia as defined previously has a

high likelihood of having an organic etiology for the

abdominal pain. Such children are ideal candidates for

referral to the pediatric gastroenterologist.

EvaluationA careful history should focus particularly on symptoms

such as epigastric abdominal pain, nocturnal pain, oral

regurgitation, heartburn, weight loss, hematemesis, and

melena. In addition, a dietary history should be obtained

in an effort to identify specific foods that increasethe pain

(fatty meals, spicy foods, lactose, and caffeine-containingbeverages). The child and family should be asked about

the use of potentially causative medications (eg, nonste-

roidal anti-inflammatory drugs, corticosteroids), alcohol,

tobacco, and acid-suppressive medications. Many chil-

dren already are being treated with over-the-counter

antacids or histamine2 (H2)-receptor antagonists. It is

important to review the doses of acid-suppressive medi-

cations being used because a lack of response may be due

to inadequate dosing or frequency of administration. On

the other hand, relief of symptoms may indicate acid-

peptic disease or functional dyspepsia. Finally, particu-

larly in teen-age females, abdominal pain, heartburn,regurgitation, weight loss, vomiting, and hematemesis

can be sentinel signs of unsuspected eating disorders.

Physical ExaminationThe physical examination begins with the vital signs and

weight and height. Anthropometric measurements

should be plotted on age- and gender-appropriate

growth curves, and current parameters compared with

previous ones if available. A funduscopic examination

should be performed in children whose predominant

complaint is emesis. Examination of the mouth and

oropharynx may demonstrate the presence of aphthous

Table 1. Major and Minor Criteriafor the Diagnosis of Dyspepsia

Major Criteria

Epigastric abdominal painRecurrent vomiting (at least 3 /mo)

Minor Criteria

Symptoms associated with eating (anorexia/weightloss)

Pain awakening the child at nightHeartburnOral regurgitationChronic nauseaExcessive belching/hiccupingEarly satietyPeriumbilical abdominal painFamily history of peptic ulcer disease, dyspepsia, or

irritable bowel syndrome

gastroenterology peptic ulcer disease

350 Pediatrics in Review Vol.22 No.10 October 2001



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ulcers (in some instances an early manifestation of Crohn

disease) or dental enamel erosion, a manifestation of

chronic gastroesophageal reflux in children.

Examination of the lungs can reveal wheezing (bron-

chospasm can be due to or exacerbated by gastroesoph-

ageal reflux). The abdomen should be palpated carefully

to determine areas of tenderness. The liver span should

be measured (to determine hepatomegaly) and the pres-

ence of an enlarged spleen documented (portal hyperten-

sion). A rectal examination also should be performed to

evaluate for perianal disease, a common finding in Crohndisease, and occult blood in feces. The fingers should be

examined for clubbing (Crohn disease) and for changes

associated with self-induced vomiting.

Laboratory StudiesLaboratory evaluations should be based on the present-

ing symptoms and findings on physical examination. The

initial evaluation should include a complete blood count

with differential count, erythrocyte sedimentation rate,

liver function test, measurement of electrolytes, and ex-

amination of the stool for ova and parasites. Finally,

particularly for females who have abdominal pain, aurinalysis and urine culture should be obtained. Further

tests are performed as indicated by the associated clinical

symptoms (Table 2).

When Should Endoscopy Be Performed?If dyspepsia is diagnosed based on the previous criteria,

results of initial screening tests are normal, and the child

has no history of hematemesis, melena, or occult blood

in the stool, a trial of H2-receptor antagonists may be

offered for 2 to 4 weeks. Lack of improvement or inabil-

ity to wean the medication due to relapse in symptoms is

an indication for upper endoscopy. Other indications for

endoscopy include the evaluation of gastrointestinal

bleeding or an abnormality found on upper gastrointes-

tinal radiographic series, odynophagia, refusal to eat, and

persistent unexplained vomiting. When an upper endos-

copy is performed, biopsies always should be obtained

from the esophagus, duodenum, and gastric antrum. If

the child already has been treated with H2-blockers or

proton pump inhibitors, biopsies of the body of the

stomach should be obtained to evaluate for the presence

ofH pylori. The finding of mild nonspecific inflammation

in the absence of H pylori infection should allow thephysician to diagnose nonulcer dyspepsia if the remain-

der of the evaluation is unremarkable.

Role of H pylori InfectionBased on prevalence studies, H pyloriis among the most

common bacterial infections in humans. In 1982, Mar-

shall and Warren successfully cultured H pylori from the

gastric antrum and proved the association of H pylori

infection with peptic ulcer disease. H pylori are gram-

negative, S-shaped rods that are 0.5 3.0 micrometers

in length and produce enzymes such as urease, catalase,

and oxidase. H pylori require a microaerobic environ-ment for culture, reflecting their environmental niche in

the semipermeable mucous layer overlying the gastric

epithelium. Although all children infected with H pylori

appear to develop chronic-active gastritis, most appar-

ently have asymptomatic infections, which may never

lead to clinically evident disease. Only a minority of

children develops peptic ulceration or gastric cancer, the

more severe manifestations ofHelicobacterinfection.

The method of acquisition and transmission of H

pyloriis unclear, although the most likely mode of trans-

mission is fecal-oral, which is supported by the finding of

viable H pylori in feces. Risk factors, such as minimal

Table 2. Additional Diagnostic Studies Based on the Primary Presenting

Signs and SymptomsSymptom/Signs Test Condition Evaluated

Vomiting Upper gastrointestinal series Gastric outlet obstruction, malrotationVomiting and abdominal pain Amylase and lipase PancreatitisRight upper quadrant pain Liver function tests/ultrasonography of

the liver and gallbladderHepatobiliary disease

Elevated erythrocytesedimentation rate, bloodin feces, anemia, weightloss

Upper gastrointestinal series withsmall bowel follow-through andcolonoscopy

Inflammatory bowel disease or other systemicinflammatory conditions

Bloating, increased burping,or flatus

Lactose hydrogen breath test Lactose intolerance and small bowel bacterialovergrowth





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education and low socioeconomic status during child-

hood, influence the prevalence. The mechanism bywhich H pyloricauses gastric inflammation is unclear, but

one factor that may account for the gastric damage is the

large amount of urease present in H pylori. Urease hy-

drolyzes urea to ammonia and bicarbonate at the gastric

mucosal surface. Ammonia can be directly toxic to epi-

thelial cells, and the concomitant increase in the mucosal

surface pH might interfere with gastric epithelial func-

tion, such as production of mucus. In addition to urease,

the H pylorivacuolating cytotoxin

has been the focus of intense in-

vestigation for several years.

Cytotoxin-producing strains tend

to be more virulent than toxin-

negative ones.

H pylori not only produces

chronic active gastritis and duode-

nal ulcers, but chronic coloniza-

tion ultimately may predispose an

individual to a significantly in-

creased risk of developing gastric

cancer or mucosa-associated lymphoid tissue (MALT)

lymphoma. H pylori has been classified as a group I

carcinogen by the World Health Organization. The rel-

ative risk of gastric carcinoma is 2.3 to 8.7 times greater

in infected adults compared with uninfected subjects.However, only 1% of H pylori-infected individuals ever

develop gastric cancer. Finally, H pylori is only one of

many risk factors in the cascade that leads to gastric

cancer and, therefore, does not yet justify the eradication

ofH pylori in early life.

The association of H pylori and recurrent abdominal

pain is more controversial. With the exception of one

study, there does not appear to be an association between

H pylori infection and an increased prevalence of recur-

rent abdominal pain. Therefore, routine evaluation for H

pylori in patients who do not have symptoms of acid-

peptic disease is not warranted. There is no clear evidencethat treatment of H pylori will alleviate symptoms in

children who have recurrent abdominal pain and H pylori

gastritis.

Diagnostic Tests for H pylori InfectionSeveral enzyme-linked immunosorbent assay-based

commercial kits that measure anti-H pyloriserum immu-

noglobulin G (IgG) antibody titers are available for

adults. The sensitivity and specificity of these tests in

children are variable and seem to depend on the test

used. Children younger than age 10 years seem to have

more false-negative serologies. Therefore, a negative se-

rology does not rule out infection in young children.

Serology also is not useful for demonstrating successfuleradication ofH pylori infection.

The 13C-urea breath test offers some important ad-

vantages over the serologic tests. It is noninvasive, easy to

perform, and easy to repeat to evaluate response to

treatment. This test measures bacterial colonization in

gastric mucosa. It currently is not approved by the

United States Food and Drug Administration for the

pediatric population.

Recently, guidelines for the diagnosis and treatment

of H pylori infection in children were endorsed by

the American Academy of Pediatrics and published

(Drumm, 2000). Based on the current available data,

these guidelines do not recommend the use of serologyor urea breath test for diagnosis of H pylori infection in

children. The guidelines only recommend endoscopy

with biopsy for the evaluation of children who have

symptoms consistent with peptic ulcer disease. The pur-

pose of the endoscopy is to identify organic etiologies for

the dyspepsia, not simply to screen for H pylori.

Treatment of Acid-Peptic DiseaseTreatment and dosing of medications are listed in Table

3. The medications prescribed for acid-peptic disease

include H2-receptor antagonists, proton pump inhibi-

tors, cytoprotective agents, and anticholinergic agents.The first-line drugs used are H2-blockers, and proton

pump inhibitors are prescribed when the patient has no

response to H2-blockers. Cytoprotective agents are use-

ful if mucosal lesions are present. Anticholinergic medi-

cations seldom are used.

H2

-Receptor AntagonistsThe most commonly used agents are cimetidine, raniti-

dine, and famotidine. These agents are highly selective,

reversible, competitive antagonists to the action of hista-

mine on H2-receptors. They decrease the volume of

gastric secretions as well as the amount of gastric acid

Recent guidelines for the diagnosisof H pylori infection in children onlyrecommend endoscopy with biopsy forevaluation of those who have symptomsconsistent with peptic ulcer disease.





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secreted. Possible side effects of cimetidine are diarrhea,

rash, myalgias, confusion, neutropenia, gynecomastia,

elevated liver function tests, and dizziness. Ranitidine

may produce headache, gastrointestinal disturbance,

malaise, insomnia, sedation, arthralgia, and hepatotoxic-

ity. Famotidine may cause headache, dizziness, constipa-

tion, diarrhea, and drowsiness.

Proton Pump InhibitorsThe proton pump inhibitors, omeprazole and lansopra-

zole, are irreversible inhibitors of H/KATPase. They

are potent inhibitors of gastric acid secretion. Potential

side effects include headache, diarrhea, nausea, and vom-

iting for omeprazole and headache and diarrhea for

lansoprazole.

Cytoprotective AgentsSucralfate is a sucrose octasulfate and polyaluminum

hydroxide complex that acts as a cytoprotective agent. It

forms a sticky gel that adheres to injured mucosa at a pHof less than 4. In the duodenum, where the pH is greater

than 4, sucralfate maintains its adherent properties. It is

contraindicated in children who have renal failure.

Anticholinergic AgentsAtropine and related anticholinergic agents have been

used for decades in the treatment of peptic ulcer disease,

but they usually are not effective as single agents. Low-

dose anticholinergic agents in adults augment the effect

of the H2-receptor antagonists on food-stimulated acid

secretion in those who have duodenal ulcers. Piranzepine

is a muscarinic antagonist agent that has selectivity for

gastric secretion but no effect on the cardiovascular

system in doses required for the treatment of acid hyper-

secretion. Imipramine, a tricyclic antidepressant agent

that has anticholinergic effects, also has been used to

inhibit gastric acid.

Table 4. Three RecommendedCombination EradicationTherapies for H pylori-associatedDisease in Children

Medications DoseDuration ofTreatment

Amoxicillin 50 mg/kg per daydivided bid

14 days

Clarithromycin 15 mg/kg per day

divided bid

14 days

Proton pump inhibitor 1 mg/kg per daydivided bid

1 month

Amoxicillin 50 mg/kg per daydivided bid

14 days

Metronidazole 20 mg/kg per daydivided bid

14 days


1 month

Clarithromycin 15 mg/kg per daydivided bid

14 days

Metronidazole 20 mg/kg per daydivided bid

14 days


1 month

Table 3. Medications Used in the Treatment of Acid-Peptic Disease

Medication Pediatric Dose How Supplied

H2

-receptor AntagonistsCimetidine 20 to 40 mg/kg per day up to 400 mg

twice dailySyrup: 300 mg/5 mL; Tablets: 200, 300,

400, and 800 mgFamotidine 1 to 1.2 mg/kg per day up to 20 mg

twice dailySyrup: 40 mg/5 mL; Tablets: 20 and 40 mg

Ranitidine 2 to 4 mg/kg per day up to 150 mgtwice daily

Syrup: 75 mg/5 mL; Tablets: 150 and300 mg

Proton Pump InhibitorsLansoprazole 0.8 mg/kg per day Capsules: 15 and 30 mgOmeprazole 0.8 mg/kg per day, effective dosage

range of 0.3 to 3.3 mg/kg per 24 hrhas been reported

Capsules: 10 and 20 mg

Cytotoprotective AgentsSucralfate 40 to 80 mg/kg per day up to 1 g

four times/daySuspension: 1 g/5 mL; Tablets: 1 g





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Treatment of H pylori Infection

Compliance is a very important factor in achieving erad-ication of H pylori in children. Several regimens have

been published, including 1-week therapy with colloidal

bismuth subcitrate, clarithromycin, and metronidazole

(eradication in 21/22 children [95%]) and 1-week treat-

ment with lansoprazole, amoxicillin, and clarithromycin

(eradication rate of 87%). Treatment for 2 weeks with

metronidazole, clarithromycin, and omeprazole was

successful in 93% of children treated. Although con-

cerns have been expressed about the use of bismuth

salts in children, none of the potential side effects has

been reported when used for the treatment ofH pylori

infection. Table 4 summarizes the three recommended

eradication therapies for H pylori-associated disease in

children.

Suggested ReadingAshorn M. Diagnosis and treatment of pediatric Helicobacter pylori

infection. Are special guidelines needed? Ital J Gastroenterol

Hepat. 1997;29:491 494

Black D, Haggitt R, Whitington P. Gastroduodenal endoscopic-

histologic correlation in pediatric patients. J Pediatr Gastroen-

terol Nutr. 1988;7:353358

Cadranel S, Bontems P, Snyder J. Consensus for the manage-

ment ofHelicobacter pyloriinfection in children: still search-

ing for a paradigm. Acta Gastro-Enterologica Belgica. 1998;

61:316 320

Czinn S. Dyspepsia in children.J Pediatr Gastroenterol Nutr. 1993;

17:237238

Debas HT. Peripheral regulation of gastric acid secretion. In:

Johnson LR II, ed. Physiology of the Gastrointestinal Tract. 2nd

ed. New York, NY: Raven Press; 1986:931945

Drumm B, Koletzko S, Oderda G. Helicobacter pyloriinfection in

children: a consensus statement. J Pediatr Gastroenterol Nutr.

2000;30:207213

Gremse D, Sacks A. Evaluation of dyspepsia. Pediatr Ann. 1997;

26:4:251259

Hua-Xiang X, Talley N. Helicobacter pylorieradication in patients

with non-ulcer dyspepsia. Drugs. 1999;5:785792

Hyman P, Hassall E. Marked basal gastric acid hypersecretion andpeptic ulcer disease: medical management with a combination

H2

histamine receptor antagonist and anticholinergic. J Pediatr

Gastroenterol Nutr. 1988;7:57 63

Kato S, Ritsuno H, Ohnuma K, Iinuma K, Sugiyama T, Asaka M.

Safety and efficacy of one-week triple therapy for eradicating

Helicobacter pyloriin children. Helicobacter. 1998;3(4)

Ranjan D, Hassall E, Jevon G, Dimmick J. Gastritis and gastropathy

of childhood. J Pediatr Gastroenterol Nutr. 1999;29:378 394

Rowland M, Imrie C, Bourke B, Drumm B. How should Helico-

bacter pyloriinfected children be managed? Gut. 1999;45(suppl

1):I36 I39





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PIR QuizQuiz also available online at www.pedsinreview.org

6. A 6-year-old boy has had intermittent periumbilical abdominal pain for the past 2 months. The pain hasawakened him frequently at night and has been associated with nausea and loss of appetite. Thesefindings are least suggestive of a diagnosis of:

A. Acid-peptic disease.B. Biliary tract disease.C. Crohn disease.D. Eosinophilic gastroenteritis.E. Functional abdominal pain.

7. A 9-year-old girl is diagnosed with dyspepsia without hematemesis, melena, or occult blood in the stool.

Results of screening tests are normal. The most appropriate next step is:A. Esophagogastroduodenoscopy.B. Trial of omeprazole.C. Trial of ranitidine.D. Trial of sulcralfate.E. Upper gastrointestinal radiographic series.

8. Helicobacter pylori infection in a child is most likely to result in:

A. Chronic active gastritis.B. Duodenal carcinoma.C. Gastric carcinoma.D. Nonulcer dypepsia.E. Peptic ulcer.

9. According to the American Academy of Pediatrics, H pylori infection in children is diagnosed mostaccurately by:

A. Biopsy.B. Hydrogen breath test.C. Serum immunoglobulin G (IgG) antibodies.D. Serum IgM antibodies.E. Urea breath test.

10. Triple therapy recommended for childhood H pylori infections always includes:

A. Aminoglycosides.B. Beta-lactams.

C. Histamine2 blockers.D. Macrolides.E. Proton pump inhibitors.





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DOI: 10.1542/pir.22-10-3492001;22;349Pediatrics in Review

Gisela Chelimsky and Steven CzinnPeptic Ulcer Disease in Children

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