tag:blogger.com,1999:blog-88462287600104973612024-02-08T06:15:38.181-08:00PEPTIC ULCER DISEASESAnonymoushttp://www.blogger.com/profile/06267357132580929345noreply@blogger.comBlogger1125tag:blogger.com,1999:blog-8846228760010497361.post-82975119038847621072013-11-02T08:38:00.004-07:002013-11-02T08:38:56.418-07:00PEPTIC ULCER DISEASES<div dir="ltr" style="text-align: left;" trbidi="on">
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">PEPTIC ULCER DISEASE</span></b><b><span lang="UK" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: UK;">
</span></b><b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"><o:p></o:p></span></b></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> History of epigastric pain present in 80-90 % of
patient, but is nonspecific.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Burning epigastric pain exacerbated
by fasting and improved with meals is a symptom complex associated with peptic
ulcer disease (PUD). <o:p></o:p></span></div>
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">An</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> <span class="emphi"><b>ulcer</b></span><b> is defined as disruption of the mucosal integrity of the stomach
and/or duodenum leading to a local defect or excavation due to active
inflammation. Ulcers occur within the stomach and/or duodenum and are often
chronic in nature.<o:p></o:p></b></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Acid peptic
disorders are very common in the <st1:country-region w:st="on"><st1:place w:st="on">United States</st1:place></st1:country-region>, with 4 million
individuals (new cases and recurrences) affected per year. Lifetime prevalence
of PUD in the <st1:country-region w:st="on"><st1:place w:st="on">United States</st1:place></st1:country-region>
is ~12% in men and 10% in women. Moreover, an estimated 15,000 deaths per year
occur as a consequence of complicated PUD. The financial impact of these common
disorders has been substantial, with an estimated burden on direct and indirect
health care costs of ~$10 billion per year in the <st1:place w:st="on"><st1:country-region w:st="on">United States</st1:country-region></st1:place>.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Why does the ulcer appear ? Let remember the physiology
of gastric<b> s</b>ecretion.<o:p></o:p></span></div>
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Physiology of
Gastric Secretion<o:p></o:p></span></b></div>
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<i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Hydrochloric acid and pepsinogen are the two
principal gastric secretory products capable of inducing mucosal injury.</span></i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> Acid
secretion should be viewed as occurring under basal and stimulated conditions.
Basal acid production occurs in a circadian pattern, with highest levels
occurring during the night and lowest levels during the morning hours.
Cholinergic input via the vagus nerve and histaminergic input from local
gastric sources are the principal contributors to basal acid secretion. <i>Stimulated gastric acid secretion occurs
primarily in three phases based on the site where the signal originates
(cephalic, gastric, and intestinal).</i> <o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
Sight, smell, and taste of food are the components of the <i>cephalic phase</i>, which stimulates gastric secretion via the vagus
nerve. <o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
The <i>gastric phase</i> is activated once
food enters the stomach. This component of secretion is driven by nutrients
(amino acids and amines) that directly stimulate the G cell to release gastrin,
which in turn activates the parietal cell via direct and indirect mechanisms.
Distention of the stomach wall also leads to gastrin release and acid
production. <o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
The <i>last phase</i> of gastric acid
secretion is initiated as <i>food</i> <i>enters the intestine</i> and is mediated by
luminal distention and nutrient assimilation. A series of pathways that inhibit
gastric acid production are also set into motion during these phases. The
gastrointestinal hormone somatostatin is released from endocrine cells found in
the gastric mucosa (D cells) in response to HCl. Somatostatin can inhibit acid
production by both direct (parietal <a href="" name="PG1748"></a>cell) and indirect
mechanisms [decreased histamine release from enterochromaffin-like (ECL) cells
and gastrin release from G cells. <u>Additional neural (central and peripheral)
and hormonal (secretin, cholecystokinin) factors play a role in
counterbalancing acid secretion. Under physiologic circumstances, these phases
are occurring simultaneously.<o:p></o:p></u></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The gastric
epithelium is under a constant assault by a series of endogenous noxious</span> <span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">factors</span> <span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">including HCl, pepsinogen/pepsin, and bile salts. In addition, a steady
flow of exogenous substances such as medications, alcohol, and bacteria
encounter the gastric mucosa. A highly intricate biologic system is in place to
provide defense from mucosal injury and to repair any injury that may occur.<o:p></o:p></span></div>
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The mucosal defense</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> system can
be envisioned as a three-level barrier, composed of preepithelial, epithelial,
and subepithelial elements. <i>The first
line of defense</i> is a mucus-bicarbonate <a href="" name="PG1747"></a>layer, which
serves as a physicochemical barrier to multiple molecules including hydrogen
ions. Mucus is secreted in a regulated fashion by gastroduodenal surface
epithelial cells. It consists primarily of water (95%) and a mixture of lipids
and glycoproteins. Mucin is the constituent glycoprotein that, in combination
with phospholipids (also secreted by gastric mucous cells), forms a hydrophobic
surface with fatty acids that extend into the lumen from the cell membrane. The
mucous gel functions as a nonstirred water layer impeding diffusion of ions and
molecules such as pepsin. Bicarbonate, secreted by surface epithelial cells of
the gastroduodenal mucosa into the mucous gel, forms a pH gradient ranging from
1 to 2 at the gastric luminal surface and reaching 6 to 7 along the epithelial
cell surface. Bicarbonate secretion is stimulated by calcium, prostaglandins,
cholinergic input, and luminal acidification.<o:p></o:p></span></div>
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<i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Surface epithelial cells provide the next line of
defense</span></i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> through several factors, including mucus production, epithelial cell
ionic transporters that maintain intracellular pH and bicarbonate production,
and intracellular tight junctions. If the preepithelial barrier were breached,
gastric epithelial cells bordering a site of injury can migrate to restore a
damaged region (<span class="emphi">restitution</span>). This process occurs
independent of cell division and requires uninterrupted blood flow and an
alkaline pH in the surrounding environment. Several growth factors including
epidermal growth factor (EGF), transforming growth factor (TGF) </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">α</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">, and basic
fibroblast growth factor (FGF) modulate the process of restitution. Larger
defects that are not effectively repaired by restitution require cell
proliferation. <i>Epithelial cell regeneration
is regulated by prostaglandins and growth factors such as EGF and TGF-</i></span><i><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">α</span></i><i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">.</span></i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> In tandem
with epithelial cell renewal, formation of new vessels (<span class="emphi">angiogenesis</span>)
within the injured microvascular bed occurs. Both FGF and vascular endothelial
growth factor (VEGF) are important in regulating angiogenesis in the gastric
mucosa.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">An elaborate
microvascular system within the gastric submucosal layer is the key component
of the subepithelial defense/repair system. A rich submucosal circulatory bed
provides HCO<sub>3</sub><sup>-</sup>, which neutralizes the acid generated by
parietal cell secretion of HCl. Moreover, this microcirculatory bed provides an
adequate supply of micronutrients and oxygen while removing toxic metabolic
by-products.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Prostaglandins
play a central role in gastric epithelial defense/repair </span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">. The
gastric mucosa contains abundant levels of prostaglandins. These metabolites of
arachidonic acid regulate the release of mucosal bicarbonate and mucus, inhibit
parietal cell secretion, and are important in maintaining mucosal blood flow
and epithelial cell restitution.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">P. <b>Seguence
of events in the pathophysiology of duodenal ulceration</b> <o:p></o:p></span></div>
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<br /></div>
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<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">PATHOPHYSIOLOGIC BASIS OF
PEPTIC ULCER DISEASE</span><o:p></o:p></div>
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<br /></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Multiple factors play a role in the
pathogenesis of PUD. The two predominant causes are <span class="emphi">H. pylori</span>
infection and NSAID ingestion. PUD not related to <span class="emphi">H. pylori</span>
or NSAIDs may be increasing. <b>Independent
of the inciting or injurious agent, peptic ulcers develop as a result of an
imbalance between mucosal protection/repair and aggressive factors.</b> Gastric
acid plays an essential role in mucosal injury.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">PUD
encompasses both gastric and duodenal ulcers.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Ulcers are defined as a break in the mucosal
surface >5 mm in size, with depth to the submucosa.</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> Duodenal
ulcers (<b>DUs</b>) and gastric ulcers (<b>GUs</b>); share many common features in
terms of pathogenesis, diagnosis, and treatment, but several factors
distinguish them from one another.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Epidemiology<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">DUODENAL
ULCERS<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">DUs are estimated to occur in 6 to
15% of the western population. The incidence of DUs declined steadily from 1960
to 1980 and has remained stable since then. The death rates, need for surgery,
and physician visits have decreased by >50% over the past 30 years. The
reason for the reduction in the frequency of DUs is likely related to the
decreasing frequency of <span class="emphi">Helicobacter pylori</span>. Before
the discovery of <span class="emphi">H. pylori</span>, the natural history of DUs
was typified by frequent recurrences after initial therapy. Eradication of <span class="emphi">H. pylori</span> has greatly reduced these recurrence rates.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<a href="" name="PG1749"></a><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">GASTRIC
ULCERS<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">GUs tend to occur later in life than
duodenal lesions, with a peak incidence reported in the sixth decade. More than
half of GUs occur in males and are less common than DUs, perhaps due to the
higher likelihood of GUs being silent and presenting only after a complication
develops. Autopsy studies suggest a similar incidence of DUs and GUs.<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">MISCELLANEOUS PATHOGENETIC FACTORS IN ACID PEPTIC
DISEASE<o:p></o:p></span></div>
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<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Cigarette
smoking has been implicated in the pathogenesis of PUD. Not only have smokers
been found to have ulcers more frequently than do nonsmokers, but smoking
appears to decrease healing rates, impair response to therapy, and increase
ulcer-related complications such as perforation. The mechanism responsible for
increased ulcer diathesis in smokers is unknown. Theories have included altered
gastric emptying, decreased proximal duodenal bicarbonate production, increased
risk for <span class="emphi">H. pylori</span> infection, and cigarette-induced
generation of noxious mucosal free radicals. Acid secretion is not abnormal in
smokers. Despite these interesting theories, a unifying mechanism for
cigarette-induced peptic ulcer diathesis has not been established.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Genetic predisposition</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> has also
been considered to play a role in ulcer development. First-degree relatives of
DU patients are three times as likely to develop an ulcer; however, the
potential role of <span class="emphi">H. pylori</span> infection in contacts is a
major consideration. Increased frequency <b>of
blood group O</b> and of the nonsecretor status have also been implicated as
genetic risk factors for peptic diathesis. However, <span class="emphi">H. pylori</span>
preferentially binds to group O antigens. Therefore, the role of genetic
predisposition in common PUD has not been established.<o:p></o:p></span></div>
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Psychological stress</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> has been
thought to contribute to PUD, but studies examining the role of psychological
factors in its pathogenesis have generated conflicting results. Although PUD is
associated with certain personality traits (<b>neuroticism)</b>, these same traits are also present in individuals
with nonulcer dyspepsia (NUD) and other functional and organic disorders.
Although more work in this area is needed, no typical PUD personality has been
found.<o:p></o:p></span></div>
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<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Diet </span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">has also been thought to play a role
in peptic diseases. Certain foods can cause dyspepsia, but no convincing
studies indicate an association between ulcer formation and a specific diet.
This is also true for beverages containing alcohol and caffeine. Specific
chronic disorders have been associated with PUD. Those with a strong association
are (1) systemic mastocytosis, (2) chronic pulmonary disease, (3) chronic renal
failure, (4) cirrhosis, (5) nephrolithiasis, and (6) </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">α</span><sub><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">1</span></sub><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-antitrypsin
deficiency. Those with a possible association are (1) hyper- parathyroidism,
(2) coronary artery disease, (3) polycythemia vera, and (4) chronic
pancreatitis.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Multiple factors play a role in the
pathogenesis of PUD. The two predominant causes are <span class="emphi">H. pylori</span>
infection and NSAID ingestion. PUD not related to <span class="emphi">H. pylori</span>
or NSAIDs may be increasing. Independent of the inciting or injurious agent,
peptic ulcers develop as a result of an imbalance between mucosal
protection/repair and aggressive factors. Gastric acid plays an essential role
in mucosal injury.<o:p></o:p></span></div>
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<br /></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Pathophysiology<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">It is now clear that <span class="emphi">H. pylori</span> and NSAID-induced injury account for the majority
of DUs. Gastric acid contributes to mucosal injury but does not play a primary
role.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">DUODENAL ULCERS<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Many acid
secretory abnormalities have been described in DU patients. Of these, average
basal and nocturnal gastric acid secretion appear to be increased in DU
patients as compared to control; however, the level of overlap between DU
patients and control subjects is substantial. The reason for this altered
secretory process is unclear, but <span class="emphi">H. pylori</span> infection
may contribute to this finding. Accelerated gastric emptying of liquids has
been noted in some DU patients but is not consistently observed; its role in DU
formation, if any, is unclear. Bicarbonate secretion is significantly decreased
in the duodenal bulb of patients with an active DU as compared to control
subjects. <span class="emphi">H. pylori</span> infection may also play a role in
this process.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">GASTRIC
ULCERS<i><o:p></o:p></i></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">As in DUs, the majority of GUs can be
attributed to either <span class="emphi">H. pylori</span> or NSAID-induced
mucosal damage. GUs that occur in the prepyloric area or those in the body
associated with a DU or a duodenal scar are similar in pathogenesis to DUs.
Gastric acid output (basal and stimulated) tends to be normal or decreased in
GU patients. When GUs develop in the presence of minimal acid levels,
impairment of mucosal defense factors may be present.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">H. PYLORI AND
ACID PEPTIC DISORDERS<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Gastric infection with the bacterium <span class="emphi">H. pylori</span> accounts for the majority of PUD. This organism also plays a role in the
development of gastric mucosal-associated lymphoid tissue (MALT) lymphoma and
gastric adenocarcinoma. Although the entire genome of <span class="emphi">H.
pylori</span> has been sequenced, it is still not clear how this organism,
which is in the stomach, causes ulceration in the duodenum, or whether its
eradication will lead to a decrease in gastric cancer.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The Bacterium</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span> <span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">initially
named <span class="emphi"><b>Campylobacter
pyloridis</b></span><b>, is a gram-negative
microaerophilic rod found most commonly in the deeper portions of the mucous
gel coating the gastric mucosa or between the mucous layer and the gastric
epithelium.</b> It may attach to gastric epithelium but under normal
circumstances does not appear to invade cells. It is strategically designed to
live within the aggressive environment of the stomach. It is S-shaped (~0.5 × 3
µm in size) and contains multiple sheathed flagella. Initially, <span class="emphi">H. pylori</span> resides in the antrum but, over time, migrates
toward the more proximal segments of the stomach.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The bacterium, initially named <span class="emphi">Campylobacter pyloridis</span>, is a gram-negative microaerophilic
rod found most commonly in the deeper portions of the mucous gel coating the
gastric mucosa or between the mucous layer and the gastric epithelium. It may
attach to gastric epithelium but under normal circumstances does not appear to
invade cells. It is strategically designed to live within the aggressive
environment of the stomach. It is S-shaped (~0.5 × 3 µm in size) and contains
multiple sheathed flagella. Initially, <span class="emphi">H. pylori</span>
resides in the antrum but, over time, migrates toward the more proximal
segments of the stomach. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Two factors that predispose to</span></i><i> </i><i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">higher colonization rates include poor
socioeconomic status and less education<o:p></o:p></span></i></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: 45.0pt;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Transmission
of <span class="emphi">H. pylori</span> occurs from person to person, following
an oral-oral or fecal-oral route. The risk of <span class="emphi">H. pylori</span>
infection is declining in developing countries. The rate of infection in the <st1:country-region w:st="on"><st1:place w:st="on">United States</st1:place></st1:country-region>
has fallen by >50% when compared to 30 years ago.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<u><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Pathophysiology<o:p></o:p></span></u></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span class="emphi"><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">H. pylori</span></span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> infection is
virtually always associated with a chronic active gastritis, but only 10 to 15%
of infected individuals develop frank peptic ulceration. The basis for this
difference is unknown. Initial studies suggested that >90% of all DUs were
associated with <span class="emphi">H. pylori</span>, but <span class="emphi">H.
pylori</span> is present in only 30 to 60% of individuals with GUs and 70% of
patients with DUs. The pathophysiology of ulcers not associated with <span class="emphi">H. pylori</span> or NSAID ingestion [or the rare Zollinger-Ellison
syndrome (ZES)] is unclear.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<a href="" name="PG1750"></a><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The
particular end result of <span class="emphi">H. pylori</span> infection
(gastritis, PUD, gastric MALT lymphoma, gastric cancer) is determined by a
complex interplay between bacterial and host factors<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">About 20,000
patients die each year from serious gastrointestinal complications from NSAIDs.
Unfortunately, dyspeptic symptoms do not correlate with NSAID-induced
pathology. Over 80% of patients with serious NSAID-related complications did
not have preceding dyspepsia. In view of the lack of warning signs, it is
important to identify patients who are at increased risk for morbidity and
mortality related to NSAID usage. Even 75 mg/d of aspirin may lead to serious
gastrointestinal ulceration, thus no dose of NSAID is completely safe.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-align: center; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Classification</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">1.
Localization<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
GU<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">- DU <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">сочетанные</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">язвы</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">желудка</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">и</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> 12-</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">перстной</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">кишки</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- гастроеюнальная
язва.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">2.
Etiology<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> - </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">Нр</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-positive<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">Нр</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">- negative<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">-
mixed (HP + other factor s: stress-, drug-induced<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">Смешанная
(НР+другой установленный этиологический фактор)<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;"> 3. Стадия (фаза) язвенного процесса:<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;"> - активная (острая, свежая)<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- рубцующаяся<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- стадия рубца<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- длительно не
рубцующаяся<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">4. Сопутствующие
морфофункциональные изменения:<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- локализация и
активность гастрита и дуоденита<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- наличие и
степень выраженности атрофии слизистой оболочки<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- наличие кишечной
метаплазии<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- наличие эрозий,
полипов<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- наличие
гастроэзофагеального или дуоденогастрального рефлюксов<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- характеристика
секреторной и моторной функции.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">5. Осложнения
(кровотечение, перфорация, пенетрация, стеноз, малигнизация).<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<i><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">Примеры формулирования диагноза:</span></i><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- ЯБ тела желудка
в активной фазе, НР- положительная, гастрит тела желудка с атрофией и кишечной
метаплазией.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span lang="RU" style="font-size: 14.0pt; line-height: 150%;">- ЯБ луковицы
12-перстной кишки в активной фазе, НР-положительная, хронический антральный гастрит, дуоденит с
выраженной желудочной метаплазией.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<br /></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">CLINICAL
FEATURES<o:p></o:p></span></b></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">History<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Abdominal
pain</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> is common to many gastrointestinal disorders, including DU and GU, but
has a poor predictive value for the presence of either DU or GU. Up to 10% of
patients with NSAID-induced mucosal disease can present with a complication
(bleeding, perforation, and obstruction) without antecedent symptoms. Despite
this poor correlation, a careful history and physical examination are essential
components of the approach to a patient suspected of having peptic ulcers.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Epigastric pain described as a burning or gnawing
discomfort can be present in both DU and GU.</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> The discomfort is also
described as an ill-defined, aching sensation or as hunger pain. The typical
pain pattern in DU occurs 90 min to 3 h after a meal and is frequently relieved
by antacids or food. Pain that awakes the patient from sleep (between midnight
and 3 A.M.) is the most discriminating symptom, with two-thirds of DU patients
describing this complaint. Unfortunately, this symptom is also present in one-third
of patients with NUD. The pain pattern in GU patients may be different from
that in DU patients, where discomfort may actually be precipitated by food. <b>Nausea and weight loss occur more commonly
in GU patients.</b> In the <st1:country-region w:st="on"><st1:place w:st="on">United
States</st1:place></st1:country-region>, endoscopy detects ulcers in <30%
of patients who have dyspepsia. Despite this, 40% of these individuals with
typical ulcer symptoms had an ulcer crater, and 40% had gastroduodenitis on
endoscopic examination.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Variation in the intensity or
distribution of the abdominal pain, as well as the onset of associated</span> <span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">symptoms such as <b>nausea and/or vomiting, may be indicative of an ulcer complication</b>.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> <i>Dyspepsia
that becomes <a href="" name="PG1752"></a>constant</i>, is no longer relieved by food or
antacids, or radiates to the back may indicate a <i>penetrating</i> ulcer (pancreas). Sudden onset of severe, generalized
abdominal pain may indicate <i>perforation</i>.
Pain worsening with meals, nausea, and vomiting of undigested food suggest <i>gastric outlet obstruction</i>. Tarry stools
or coffee ground emesis indicate bleeding.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<u><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Physical Examination<o:p></o:p></span></u></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Epigastric tenderness is the most
frequent finding in patients with GU or DU. Pain may be found to the right of
the midline in 20% of patients. Unfortunately, the predictive value of this
finding is rather low. Physical examination is critically important for
discovering evidence of ulcer complication. Tachycardia and orthostasis suggest
dehydration secondary to vomiting or active gastrointestinal blood loss. A
severely tender, boardlike abdomen suggests a perforation. Presence of a
succussion splash indicates retained fluid in the stomach, suggesting gastric
outlet obstruction.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center; text-indent: .5in;">
<b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">Diagnostic Evaluation</span></b><b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"><o:p></o:p></span></b></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Including such methods as<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Barium studies</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> of the proximal
gastrointestinal tract,<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Endoscopy<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Several biopsy urease tests<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Serologic testing,<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The <sup>13</sup>C- or <sup>14</sup>C-urea breath
test (UBT), <o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">and the fecal <span class="emphi">H. pylori</span>
antigen test<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">In view of
the poor predictive value of abdominal pain for the presence of a
gastroduodenal ulcer and the multiple disease processes that can mimic this
disease, the clinician is often confronted with having to establish the
presence of an ulcer. Documentation of an ulcer requires either a radiographic
(barium study) or an endoscopic procedure. However, a large percentage of
patients with symptoms suggestive of an ulcer have NUD; empirical therapy is
appropriate for individuals who are otherwise healthy and <45, before
embarking on a diagnostic evaluation.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Barium
studies</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> of the proximal gastrointestinal tract are still commonly used as a
first test for documenting an ulcer. The sensitivity of older single-contrast
barium meals for detecting a DU is as high as 80%, with a double-contrast study
providing detection rates as high as 90%. Sensitivity for detection is
decreased in small ulcers (<0.5 cm), presence of previous scarring, or in
postoperative patients. A DU appears as a well-demarcated crater, most often
seen in the bulb. A GU may represent benign or malignant disease. Typically, a
benign GU also appears as a discrete crater with radiating mucosal folds
originating from the ulcer margin. Ulcers >3 cm in size or those associated
with a mass are more often malignant. Unfortunately, up to 8% of GUs that
appear to be benign by radiographic appearance are malignant by endoscopy or
surgery. Radiographic studies that show a GU must be followed by endoscopy and
biopsy.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Endoscopy</span></b><i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">
</span></i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">provides the most sensitive and specific approach for examining the
upper gastrointestinal tract. In addition to permitting direct visualization of
the mucosa, endoscopy facilitates photographic documentation of a mucosal defect
and tissue biopsy to rule out malignancy (GU) or <span class="emphi">H. pylori</span>.
<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> <u>Tests for <span class="emphi">H.
pylori</span> can be divided into <b>two
groups</b>: <b>invasive tests</b>, which
require upper gastrointestinal endoscopy and are based on the analysis of
gastric biopsy specimens, <b>and noninvasive
tests</b>.<o:p></o:p></u></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> Although the methods for diagnosing <span class="emphi">H. pylori </span>a brief summary will be included here (</span><a href="" name="to-T1-274"></a><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#T1-274#T1-274" title="Table 274-1"><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Table</span></a><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">). Several
biopsy urease tests have been developed (PyloriTek, Clotest, Hpfast, Pronto
Dry) and have a sensitivity and specificity of >90 to 95%. Several
noninvasive methods for detecting this organism have been developed. Three
types of studies routinely used include
serologic testing, the <sup>13</sup>C- or <sup>14</sup>C-urea breath test
(UBT), and the fecal <span class="emphi">H. pylori</span> antigen test.<o:p></o:p></span></div>
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable">
<tbody>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="font-size: 14.0pt;"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#T1-274#T1-274" title="Table 274-1"><span lang="EN-US">Table</span></a></span><span class="emphbit"><b> Tests for Detection
of H. pylori</b></span><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="mso-cellspacing: 0in; mso-padding-alt: 0in 0in 0in 0in; width: 100%px;">
<tbody>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span lang="RU">Test</span></i></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span lang="RU">Sensitivity/Specificity, %</span></i></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span lang="RU">Comments</span></i></b></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU">INVASIVE (ENDOSCOPY/BIOPSY REQUIRED)</span></i></b></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Rapid urease</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">80–95/95–100</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Simple, false
negative with recent use of PPIs, antibiotics, or bismuth compounds<o:p></o:p></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Histology</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">80–90/>95</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Requires pathology
processing and staining; provides histologic information<o:p></o:p></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Culture</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">—/—</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Time-consuming,
expensive, dependent on experience; allows determination of antibiotic
susceptibility<o:p></o:p></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU">NON-INVASIVE</span></i></b></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Serology</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">>80/>90</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Inexpensive,
convenient; not useful for early follow-up<o:p></o:p></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Urea breath test</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">>90/>90</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Simple, rapid;
useful for early follow-up; false negatives with recent therapy; exposure
to low-dose radiation with <sup>14</sup>C test<o:p></o:p></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU">Stool antigen</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">>90/>90</span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
Inexpensive,
convenient; not established for eradication but promising<o:p></o:p></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i>Note</i></b>: PPIs, proton pump inhibitors.<o:p></o:p></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal">
<span lang="RU"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#to-T1-274#to-T1-274"><span style="text-decoration: none; text-underline: none;"><!--[if gte vml 1]><v:shape
id="_x0000_i1045" type="#_x0000_t75" alt="" style='width:24pt;height:24pt'
o:button="t"/><![endif]--><!--[if !vml]--><img border="0" height="32" src="file:///C:/Users/rockz/AppData/Local/Temp/msohtmlclip1/01/clip_image005.gif" v:shapes="_x0000_i1045" width="32" /><!--[endif]--></span></a></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Endoscopy</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> often is not performed in the
initial management of young dyspeptic patients without worrying symptoms but <b>is commonly used in older people to exclude
malignancy.</b> If endoscopy is performed, the most convenient biopsy-based
test is the biopsy urease test, in which one large or two small antral biopsy
specimens are placed into a gel containing urea and an indicator. The presence
of <span class="emphi">H. pylori</span> urease elicits a color change, which
often occurs within minutes but can require up to 24 h. Histologic examination
of biopsy specimens is accurate, provided that a special stain (e.g., a
modified Giemsa or silver stain) permitting optimal visualization of <span class="emphi">H. pylori</span> is used. If biopsies from both antrum and corpus
are obtained, histologic study yields additional information, including the
degree and pattern of inflammation, atrophy, metaplasia, and dysplasia.
Microbiologic culture is most specific but may be insensitive because of
difficulty with <span class="emphi">H. pylori</span> isolation. Once cultured,
the identity of <span class="emphi">H. pylori</span> can be confirmed by its
typical appearance on Gram's stain and its positive reactions in oxidase,
catalase, and urease tests. Moreover, the organism's antibiotic sensitivities
can be determined. The occasional biopsy specimens containing the less common
non-<span class="emphi">pylori</span> helicobacters give only weakly positive
results in the biopsy urease test. Positive identification of these bacteria
requires visualization of the characteristic long, tight spiral bacteria in
histologic sections.<o:p></o:p></span></div>
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable">
<tbody>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span class="emphbit"><b><span style="color: blue; mso-ansi-language: EN-US;">TABLE 135-1
Tests Commonly Used to Detect Helicobacter pylori</span></b></span><b><span style="color: blue; mso-ansi-language: EN-US;"><o:p></o:p></span></b></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="mso-cellspacing: 0in; mso-padding-alt: 0in 0in 0in 0in; width: 100%px;">
<tbody>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU" style="color: blue;">Test</span></i></b><span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU" style="color: blue;">Advantages</span></i></b><span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU" style="color: blue;">Disadvantages</span></i></b><span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<i><span style="color: blue; mso-ansi-language: EN-US;">INVASIVE
(BASED ON ENDOSCOPIC BIOPSY)</span></i><span style="color: blue; mso-ansi-language: EN-US;"> <o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Biopsy urease test<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Quick, simple<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Some
commercial tests not fully sensitive before 24 h<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Histology<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">May
give additional histologic information<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Sensitivity
dependent on experience and use of special stains<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Culture<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Permits
determination of antibiotic susceptibility<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Sensitivity dependent
on experience<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<i><span lang="RU" style="color: blue;">NONINVASIVE</span></i><span lang="RU" style="color: blue;"> <o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Serology<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Inexpensive and
convenient<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Cannot
be used for early follow-up; some commercial kits inaccurate<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<sup><span style="color: blue; mso-ansi-language: EN-US;">13</span></sup><span style="color: blue; mso-ansi-language: EN-US;">C or <sup>14</sup>C urea breath
test<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Inexpensive
and simpler than endoscopy; useful for follow-up after treatment<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Low-dose
irradiation in <sup>14</sup>C test<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="color: blue;">Stool antigen test<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Inexpensive
and convenient; useful for follow-up after treatment; may be useful in
children<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">New
test; role not fully established; appears less accurate than urea breath
test<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjoibnjan00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b002c8f9dcd.htm#to-T1-135#to-T1-135"><span style="text-decoration: none; text-underline: none;"><!--[if gte vml 1]><v:shape
id="_x0000_i1046" type="#_x0000_t75" alt="" style='width:24pt;height:24pt'
o:button="t"/><![endif]--><!--[if !vml]--><img border="0" height="32" src="file:///C:/Users/rockz/AppData/Local/Temp/msohtmlclip1/01/clip_image005.gif" v:shapes="_x0000_i1046" width="32" /><!--[endif]--></span></a><o:p></o:p></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Noninvasive <span class="emphi">H.
pylori</span> testing is now the norm if gastric cancer does not need to be
excluded. The most consistently accurate test is the urea breath test. In this
simple test, the patient drinks a labeled urea solution and then blows into a
tube. The urea is labeled with either the nonradioactive isotope <sup>13</sup>C
or a minute dose of the radioactive isotope <sup>14</sup>C. If <span class="emphi">H. pylori</span> urease is present, the urea is hydrolyzed and
labeled carbon dioxide is detected in breath samples. The stool antigen test is
another simple assay that is dependent on the detection of <span class="emphi">H.
pylori</span> antigens in stool. It is more convenient and less expensive than
the urea breath test but has been slightly less accurate in some <a href="" name="PG888"></a>comparative
studies. The urea breath test, the stool antigen test, and biopsy-based tests
can all be used to assess the success of treatment. However, because these
tests are dependent on <span class="emphi">H. pylori</span> load, their use <4
weeks after treatment may lead to false-negative results. These tests are also
unreliable if performed within 4 weeks of intercurrent treatment with
antibiotics or bismuth compounds or within 2 weeks of the discontinuation of
PPI treatment. In the assessment of treatment success, noninvasive tests are
normally preferred; however, after gastric ulceration, endoscopy should be
repeated to ensure healing and to exclude gastric carcinoma by further
histologic sampling.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none;">
<span style="color: #0070c0; font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Occasionally,
specialized testing such as serum gastrin and gastric acid analysis or sham
feeding may be needed in individuals with complicated or refractory PUD (see
“Zollinger-Ellison Syndrome,” below). Screening for aspirin or NSAIDS (blood or
urine) may also be necessary in refractory <span class="emphi">H. pylori</span>–negative
PUD patients.<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<b>TREATMENT<span lang="RU"><o:p></o:p></span></b></div>
<div class="MsoNormal" style="margin-left: .5in; mso-list: l3 level1 lfo1; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">•<span style="font-size: 7pt;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">The aims of management are: <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">- to relieve symptoms, <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">- induce ulcer healing in the short term, <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-left: .5in; mso-list: l2 level1 lfo2; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">-<span style="font-size: 7pt;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">cure the ulcer in the long term. <o:p></o:p></span></div>
<div class="MsoNormal">
<i><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"> <b>H. pylori</b></span></i><b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"> eradication is the
cornerstone</span></b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">
of therapy for peptic ulcers, as this will successfully prevent relapse and
eliminate the need for long-term therapy in the majority of patients. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Before the
discovery of <span class="emphi">H. pylori</span>, the therapy of PUD disease was
centered on the old dictum by Schwartz of “no acid, no ulcer.” Although <a href="" name="PG1753"></a>acid secretion is still important in the pathogenesis of PUD,
eradication of <span class="emphi">H. pylori</span> and therapy/prevention of
NSAID-induced disease is the mainstay. A summary of commonly used drugs for
treatment of acid peptic disorders is shown in </span><a href="" name="to-T2-274"></a><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#T2-274#T2-274" title="Table 274-2"><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Table </span></a><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">.<o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<br /></div>
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable">
<tbody>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<table border="1" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="border-collapse: collapse; border: none; mso-border-alt: solid windowtext .5pt; mso-border-insideh: .5pt solid windowtext; mso-border-insidev: .5pt solid windowtext; mso-padding-alt: 0in 5.4pt 0in 5.4pt; mso-yfti-tbllook: 480;">
<tbody>
<tr>
<td style="border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 93.4pt;" valign="top" width="156">
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
<td style="border-left: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 93.4pt;" valign="top" width="156">
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
<td style="border-left: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 93.4pt;" valign="top" width="156">
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
<td style="border-left: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 93.4pt;" valign="top" width="156">
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
<td style="border-left: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 93.4pt;" valign="top" width="156">
<div align="center" class="MsoNormal" style="text-align: center;">
<br /></div>
</td>
</tr>
</tbody></table>
<div align="center" class="MsoNormal" style="text-align: center;">
<span class="emphbit"><b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">TABLE. Drugs Used in the Treatment of Peptic Ulcer
Disease</span></b></span><b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></b></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="mso-cellspacing: 0in; mso-padding-alt: 0in 0in 0in 0in; width: 100%px;">
<tbody>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="font-size: 14.0pt;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Drug Type/Mechanism</span></i></b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Examples</span></i></b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="bottom">
<div class="MsoNormal">
<b><i><span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Dose</span></i></b><span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="font-size: 14.0pt;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Acid-suppressing
drugs<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<br /></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<br /></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;"> Antacids<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Mylanta,
Maalox, Tums, Gaviscon<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">100–140
meq/L 1 and 3 h after meals and hs<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;"> </span><b><span lang="RU" style="font-size: 14.0pt;">H<sub>2</sub>
receptor antagonists<o:p></o:p></span></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">Cimetidine<br />
Ranitidine<br />
Famotidine<br />
Nizatidine<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">400
mg bid<br />
300 mg hs<br />
40 mg hs<br />
300 mg hs<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;"> </span><b><span lang="RU" style="font-size: 14.0pt;">Proton
pump inhibitors<o:p></o:p></span></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Omeprazole<br />
Lansoprazole<br />
Rabeprazole<br />
Pantoprazole<br />
Esomeprazole<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">20
mg/d<br />
30 mg/d<br />
20 mg/d<br />
40 mg/d<br />
20 mg/d<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">Mucosal
protective agents<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<br /></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<br /></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><span lang="RU" style="font-size: 14.0pt;"> Sucralfate<o:p></o:p></span></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">Sucralfate<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">1 g qid<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><span lang="RU" style="font-size: 14.0pt;"> Prostaglandin analogue<o:p></o:p></span></b></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">Misoprostol<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">200 µg qid<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;"> Bismuth-containing
compounds<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;">Bismuth
subsalicylate (BSS)<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">See
anti-<i>H. pylori</i> regimens <o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="3" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="font-size: 14.0pt;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;"><o:p></o:p></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal">
<span lang="RU" style="font-size: 14.0pt;"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#to-T2-274#to-T2-274"><span style="text-decoration: none; text-underline: none;"><!--[if gte vml 1]><v:shape
id="_x0000_i1047" type="#_x0000_t75" alt="" style='width:24pt;height:24pt'
o:button="t"/><![endif]--><!--[if !vml]--><img border="0" height="32" src="file:///C:/Users/rockz/AppData/Local/Temp/msohtmlclip1/01/clip_image005.gif" v:shapes="_x0000_i1047" width="32" /><!--[endif]--></span></a><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div align="center" class="MsoNormal" style="text-align: center;">
<span class="emphbit"><b>Regimens Recommended
for Eradication of H. pylori Infection<o:p></o:p></b></span></div>
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="mso-cellspacing: 0in; mso-padding-alt: 0in 0in 0in 0in; width: 100%px;">
<tbody>
<tr>
<td colspan="2" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU">TRIPLE THERAPY</span></i></b></div>
</td>
</tr>
<tr>
<td colspan="2" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
</div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in; width: 61.38%;" valign="top" width="61%">
<div class="MsoNormal">
1. Pantoprazol
<i>plus</i><br />
Metronidazole <i>plus</i><br />
Amoxicillin<sup><span lang="RU"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#N3-T3-274#N3-T3-274" title="c"><span lang="EN-US">c</span></a></span></sup><sup> </sup>2 weeks<o:p></o:p></div>
</td>
<td style="padding: 0in 0in 0in 0in; width: 38.62%;" valign="top" width="38%">
<div class="MsoNormal">
40 mg bid<br />
500 mg tid<br />
500 mg qid<o:p></o:p></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in; width: 61.38%;" valign="top" width="61%">
<div class="MsoNormal">
2. Pantoprazole
(lansoprazole) <i>plus</i><br />
Clarithromycin <i>plus</i><br />
Metronidazole<i> 1 week</i><br />
<o:p></o:p></div>
</td>
<td style="padding: 0in 0in 0in 0in; width: 38.62%;" valign="top" width="38%">
<div class="MsoNormal">
40 mg bid (30 mg
bid)<br />
500 mg bid<br />
500 mg bid<br />
<!--[if !supportLineBreakNewLine]--><br />
<!--[endif]--><o:p></o:p></div>
</td>
</tr>
</tbody></table>
<div align="center" class="MsoNormal" style="text-align: center;">
<b><o:p></o:p></b></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Triple therapy</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">, although effective, has
several drawbacks, including the potential for poor patient compliance and
drug-induced side effects. Compliance is being addressed somewhat by simplifying
the regimens so that patients can take the medications twice a day.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="color: blue; font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Two
anti-<span class="emphi">H. pylori</span> regimens are available in prepackaged
formulation: Prevpac (lansoprazole, clarithromycin, and amoxicillin) and
Helidac (bismuth subsalicylate, tetracycline, and metronidazole)</span><span style="color: blue; mso-ansi-language: EN-US;">. </span><span style="color: blue; font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The contents of the
Prevpac are to be taken twice per day for 14 days, whereas Helidac constituents
are taken four times per day with an antisecretory agent (PPI or H<sub>2</sub>
blocker), also taken for at least 14 days.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<a href="" name="PG1755"></a><span style="color: #0070c0; font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">One
important concern with treating patients who may not need treatment is the
potential for development of antibiotic-resistant strains. The incidence and
type of antibiotic-resistant <span class="emphi">H. pylori</span> strains vary
worldwide. Strains resistant to metronidazole, clarithromycin, amoxicillin, and
tetracycline have been described, with the latter two being uncommon.
Antibiotic-resistant strains are the most common cause for treatment failure in
compliant patients. Unfortunately, in vitro resistance does not predict outcome
in patients. Culture and sensitivity testing of <span class="emphi">H. pylori</span>
is not performed routinely. Although resistance to metronidazole has been found
in as many as 30% and 95% of isolates in North America and Asia, respectively,
triple therapy is effective in eradicating the organism in >50% of patients
infected with a resistant strain. Clarithromycin resistance is seen in about
10% of persons in the United States.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Failure of <span class="emphi">H. pylori</span> eradication
with triple therapy is usually due to infection with a resistant organism.</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> <b>Quadruple therapy</b> (</span><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">), where clarithromycin is substituted for
metronidazole (or vice versa), should be the next step. <o:p></o:p></span></div>
<table border="0" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="mso-cellspacing: 0in; mso-padding-alt: 0in 0in 0in 0in; width: 100%px;">
<tbody>
<tr>
<td colspan="2" style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<b><i><span lang="RU" style="color: blue;">QUADRUPLE THERAPY</span></i></b><span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="2" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">Pantoprazole<br />
Bismuth subsalicylate<br />
Metronidazole<br />
Tetracycline<o:p></o:p></span></div>
</td>
<td style="padding: 0in 0in 0in 0in;" valign="top">
<div class="MsoNormal">
<span style="color: blue; mso-ansi-language: EN-US;">40 mg bid<br />
120 mg qid<br />
500 mg qid<br />
500 mg qid<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td colspan="2" style="padding: 0in 0in 0in 0in;">
<div align="center" class="MsoNormal" style="text-align: center;">
<span lang="RU" style="color: blue;">
<hr align="center" size="3" width="100%" />
</span></div>
<div class="MsoNormal">
<span lang="RU" style="color: blue;"><o:p></o:p></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">SIDE-EFFECTS
of IPP</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l0 level1 lfo3; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Hipergastrinemia </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l0 level1 lfo3; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Diarrhoea </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l0 level1 lfo3; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Headache </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l0 level1 lfo3; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Rashes </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l0 level1 lfo3; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Interection with warfarin, phenytoin, fewer drugs<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; margin-left: .25in; text-align: center;">
<b><i><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Side
effects</span></i></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> of therapy<b><span style="color: #0070c0;"><o:p></o:p></span></b></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .25in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">have been
reported in up to 20 to 30% of patients on triple therapy. Bismuth may cause
black stools, constipation, or darkening of the tongue. The most feared
complication with amoxicillin <b>is
pseudomembranous colitis</b>, but this occurs in <1 to 2% of patients.
Amoxicillin can also lead to antibiotic-associated diarrhea, nausea, vomiting,
skin rash, and allergic <span style="color: #0070c0;">reaction. <b>Tetracycline has been reported to cause
rashes and very rarely hepatotoxicity and anaphylaxis.<o:p></o:p></b></span></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l4 level1 lfo4; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Prostaglandins
e</span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">xert complex In low doses protect against injury induced by aspirin and
NSAIDs by enhancing mucosal blood flow, and by stimulating mucus and
bicarbonate secretion and epithelial cell proliferation. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l4 level1 lfo4; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">At high doses acid secretion is inhibited. <b>Misoprostol
</b>is effective for the prevention and treatment of NSAID-induced ulcers, but
in clinical practice IPP are preferred, since they are at least as effective
and have fewer side-effects. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Once an ulcer
(GU or DU) is documented, then the main issue at stake is whether <span class="emphi">H. pylori</span> or an NSAID is involved. With <span class="emphi">H.
pylori</span> present, independent of the NSAID status, triple therapy is
recommended for 14 days, followed by continued acid-suppressing drugs (H<sub>2</sub>
receptor antagonist or PPIs) for a total of 4 to 6 weeks. Selection of patients
for documentation of <span class="emphi">H. pylori</span> eradication (organisms
gone at least 4 weeks after completing antibiotics) is an area of some debate.
The test of choice for documenting eradication is the UBT. The stool antigen
study may also hold promise for this purpose, but the data have not been as
clear cut as in the case of using the stool antigen test for primary diagnosis.
Further studies are warranted, but if the UBT is not available, a stool antigen
should be considered to document eradication. Serologic testing is not useful
for the purpose of documenting eradication since antibody titers fall slowly
and often do not become undetectable. Two approaches toward documentation of
eradication exist: (1) test for eradication only in individuals with a
complicated course or in individuals who are frail or with multisystem disease
who would do poorly with an ulcer recurrence, and (2) test all patients for
successful eradication. Some recommend that patients with complicated ulcer
disease or who are frail should be treated with long-term acid suppression,
thus making documentation of <span class="emphi">H. pylori</span> eradication a
moot point. In view of this discrepancy in practice, it would be best to
discuss with the patient the different options available.</span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">If the ulcer
has closed, but the tests on H.P. stayed positive, recommended<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Long-term
supported antirelaps therapy<o:p></o:p></span></b></div>
<table border="1" cellpadding="0" cellspacing="0" class="MsoNormalTable" style="border-collapse: collapse; border: none; mso-border-alt: solid windowtext .5pt; mso-border-insideh: .5pt solid windowtext; mso-border-insidev: .5pt solid windowtext; mso-padding-alt: 0in 5.4pt 0in 5.4pt; mso-yfti-tbllook: 480;">
<tbody>
<tr>
<td style="border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.25pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Long-term treatment<o:p></o:p></span></div>
</td>
<td style="border-left: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.3pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">3 year for DUs and 2 year for Gus<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Ranitidine 150mg to night or<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Pantoprazole 20-40 mg before
breacfest<o:p></o:p></span></div>
</td>
</tr>
<tr style="height: 14.2pt; mso-yfti-irow: 1;">
<td style="border-top: none; border: solid windowtext 1.0pt; height: 14.2pt; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.25pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">On demand treatment (for DUs)<o:p></o:p></span></div>
</td>
<td style="border-bottom: solid windowtext 1.0pt; border-left: none; border-right: solid windowtext 1.0pt; border-top: none; height: 14.2pt; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.3pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">3-4 days whole dose of medicine,
and after – in a half-dose 2 weeks<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="border-top: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.25pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Intermittent therapy<o:p></o:p></span></div>
</td>
<td style="border-bottom: solid windowtext 1.0pt; border-left: none; border-right: solid windowtext 1.0pt; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.3pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">according to endoscopy (ulcer)<o:p></o:p></span></div>
</td>
</tr>
<tr>
<td style="border-top: none; border: solid windowtext 1.0pt; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.25pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Week-end therapy<o:p></o:p></span></div>
</td>
<td style="border-bottom: solid windowtext 1.0pt; border-left: none; border-right: solid windowtext 1.0pt; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt 0in 5.4pt; width: 239.3pt;" valign="top" width="399">
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Treatment in Friday, Saturday,
Sunday <o:p></o:p></span></div>
</td>
</tr>
</tbody></table>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Several
issues differentiate the approach to a GU versus a DU. GUs, <a href="" name="PG1756"></a>especially
of the body and fundus, have the potential of being malignant. Multiple
biopsies of a GU should be taken initially; even if these are negative for
neoplasm, repeat endoscopy to document healing at 8 to 12 weeks should be
performed, with biopsy if the ulcer is still present. About 70% of GUs
eventually found to be malignant undergo significant (usually incomplete)
healing.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The
majority (>90%) of GUs and DUs heal with the conventional therapy outlined
above. <i>A GU that fails to heal after 12
weeks and a DU that does not heal after 8 weeks of therapy should be considered
refractory. Once poor compliance and persistent <span class="emphi">H. pylori</span>
infection have been excluded, NSAID use, either inadvertent or surreptitious,
must be excluded.</i> In addition, cigarette smoking must be eliminated. For a
GU, malignancy must be meticulously excluded. Next, consideration should be
given to a gastric hypersecretory state, which can be excluded with gastric
acid analysis. Although a subset of patients have gastric acid hypersecretion
of unclear etiology as a contributing factor to refractory ulcers, ZES should
be excluded with a fasting gastrin or secretin stimulation test (see below).
More than 90% of refractory ulcers (either DUs or GUs) heal after 8 weeks of
treatment with higher doses of PPI (omeprazole, 40 mg/d; lansoprazole 30 to 60
mg/d). This higher dose is also effective in maintaining remission. Surgical
intervention may be a consideration at this point; however, other rare causes
of refractory ulcers must be excluded before recommending surgery. Rare
etiologies of refractory ulcers that may be diagnosed by gastric or duodenal
biopsies include: ischemia, Crohn's disease, amyloidosis, sarcoidosis,
lymphoma, eosinophilic gastroenteritis, or infection [cytomegalovirus (CMV),
tuberculosis, or syphilis].<o:p></o:p></span></div>
<div align="center" class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-align: center; text-indent: .5in;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">COMPLICATION<br />
of peptic ulcer disease<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l5 level1 lfo5; mso-pagination: none; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">perforation,</span></b><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span></b><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l5 level1 lfo5; mso-pagination: none; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"> gastric outlet obstruction</span></b><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> </span></b><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l5 level1 lfo5; mso-pagination: none; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"> bleeding. <o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; mso-pagination: none; text-indent: .5in;">
<br /></div>
<div align="center" class="MsoNormal" style="line-height: 150%; text-align: center;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Surgical Therapy<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Surgical intervention in PUD can be
viewed as being either elective, for treatment of medically refractory disease,
or as urgent/emergent, for the treatment of an ulcer-related complication. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; margin-left: .5in; mso-list: l1 level1 lfo6; tab-stops: list .5in; text-indent: -.25in;">
<!--[if !supportLists]--><span lang="RU" style="font-size: 14.0pt; line-height: 150%;">•<span style="font-size: 7pt; line-height: normal;">
</span></span><!--[endif]--><b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">EMERGENCY </span></b><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> - Perforation </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> - Haemorrhage </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">
<b>ELECTIVE </b></span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> - </span></b><span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Gastric outflow obstruction </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;"> - Recurrent ulcer following gastric surgery </span><span lang="RU" style="font-size: 14.0pt; line-height: 150%;"><o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">The development of pharmacologic and
endoscopic approaches for the treatment of peptic disease has led to a
substantial decrease in the number operations needed for this disorder.
Refractory ulcers are an exceedingly rare occurrence. Surgery is more often
required for treatment of an ulcer-related complication. Gastrointestinal
bleeding perforation, and gastric outlet obstruction are the three complications
that may require surgical intervention.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="color: blue; font-size: 14.0pt; line-height: 150%; mso-ansi-language: EN-US;">Examples of clinical
diagnosis:<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-size: 14.0pt; mso-ansi-language: EN-US;">Duodenal
ulcer disease, active study, HP-positive<o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
ZOLLINGER–ELLISON
SYNDROME<o:p></o:p></div>
<div class="MsoNormal">
Severe peptic ulcer
diathesis secondary to gastric acid hypersecretion due to unregulated gastrin
release from a non-<span lang="RU">β</span> cell endocrine tumor (gastrinoma) defines the components of the ZES.
Initially, ZES was typified by aggressive and refractory ulceration in which
total gastrectomy provided the only chance for enhancing survival. Today ZES
can be cured by surgical resection in up to 30% of patients.<o:p></o:p></div>
<div class="MsoNormal">
Clinical
Manifestations<o:p></o:p></div>
<div class="MsoNormal">
Gastric acid
hypersecretion is responsible for the signs and symptoms observed in patients
with ZES. Peptic ulcer is the most common clinical manifestation, occurring in
>90% of gastrinoma patients. Initial presentation and ulcer location
(duodenal bulb) may be indistinguishable from common PUD. Clinical situations
that should create suspicion of gastrinoma are ulcers in unusual locations
(second part of the duodenum and beyond), ulcers refractory to standard medical
therapy, ulcer recurrence after acid-reducing surgery, ulcers presenting with
frank complications (bleeding, obstruction, and perforation), or ulcers in the
absence of <span class="emphi">H. pylori</span> or NSAID ingestion. Symptoms of
esophageal origin are present in up to two-thirds of patients with ZES, with a
spectrum ranging from mild esophagitis to frank ulceration with stricture and
Barrett's mucosa.<o:p></o:p></div>
<div class="MsoNormal">
Diarrhea is the next
most common clinical manifestation, in up to 50% of patients. Although diarrhea
often occurs concomitantly with acid peptic disease, it may also occur
independent of an ulcer. Etiology of the diarrhea is multifactorial, resulting
from marked volume overload to the small bowel, pancreatic enzyme inactivation
by acid, and damage of the intestinal epithelial surface by acid. The
epithelial damage can lead to a mild degree of maldigestion and malabsorption
of nutrients. The diarrhea may also have a secretory component due to the
direct stimulatory effect of gastrin on enterocytes or the cosecretion of
additional hormones from the tumor, such as vasoactive intestinal peptide.<o:p></o:p></div>
<div class="MsoNormal">
Diagnosis<o:p></o:p></div>
<div class="MsoNormal">
The first step in the
evaluation of a patient suspected of having ZES is to obtain a fasting gastrin
level. A list of clinical scenarios that should arouse suspicion regarding this
diagnosis is shown in <a href="" name="to-T5-274"></a><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#T5-274#T5-274" title="Table 274-5">Table 274-5</a>. Fasting gastrin levels are usually <150
pg/mL. Virtually all gastrinoma patients will have a gastrin level >150 to
200 pg/mL. Measurement of fasting gastrin should be repeated to confirm the
clinical suspicion.<o:p></o:p></div>
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<span class="emphbit"><b>TABLE 274-5 When to
Obtain a Fasting Serum Gastrin Level</b></span><b><o:p></o:p></b></div>
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Multiple ulcers<br />
Ulcers in unusual locations; associated with severe esophagitis; resistant
to therapy with frequent recurrences; in the absence of NSAID ingestion or <i>H.
pylori</i> infection<br />
Ulcer patients awaiting surgery<br />
Extensive family history for peptic ulcer disease<br />
Postoperative ulcer recurrence<br />
Basal hyperchlorhydria<br />
Unexplained diarrhea or steatorrhea<br />
Hypercalcemia<br />
Family history of pancreatic islet, pituitary, or parathyroid tumor<br />
Prominent gastric or duodenal folds<o:p></o:p></div>
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<span lang="RU"><a href="mk:@MSITStore:C:\Documents%20and%20Settings\%D0%90%D0%B4%D0%BC%D0%B8%D0%BD%D0%B8%D1%81%D1%82%D1%80%D0%B0%D1%82%D0%BE%D1%80\%D0%A0%D0%B0%D0%B1%D0%BE%D1%87%D0%B8%D0%B9%20%D1%81%D1%82%D0%BE%D0%BB\HARRISON%2016.chm::/Harrison/gateway.ut.ovid.com/gw1/ovidweb.cgi@targetframe=1&s=idnjhkjocepbdp00d&book+content=s.sh.2.14.15_257c1_257c00000000_257c_257cgohere_257c_2fct%7b0b44400df0.htm#to-T5-274#to-T5-274"><span style="text-decoration: none; text-underline: none;"><!--[if gte vml 1]><v:shape
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The next step in establishing
a biochemical diagnosis of gastrinoma is to assess acid secretion. Nothing
further needs to be done if decreased acid output is observed. In contrast,
normal or elevated gastric acid output suggests a need for additional tests.
Gastric acid analysis is performed by placing a nasogastric tube in the stomach
and drawing samples at 15-min intervals for 1 h during unstimulated or basal
state (BAO), followed by continued sampling after administration of intravenous
pentagastrin (MAO). Up to 90% of gastrinoma patients may have a BAO of ≥15
meq/h (normal, <4 meq/h). Up to 12% of patients with common PUD may have
comparable levels of acid secretion. A BAO/MAO ratio >0.6 is highly
suggestive of ZES, but a ratio <0.6 does not exclude the diagnosis. Pentagastrin
is no longer available in the <st1:country-region w:st="on">United
States</st1:country-region>, making measurement of MAO virtually
impossible. If the technology for measuring gastric acid secretion is not
available, a basal gastric pH ≥3 virtually excludes a gastrinoma.<o:p></o:p></div>
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TREATMENT<o:p></o:p></div>
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Treatment of
functional endocrine tumors is directed at ameliorating the signs and symptoms
related to hormone overproduction, curative resection of the neoplasm, and
attempts to control tumor growth in metastatic disease.<o:p></o:p></div>
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PPIs are the treatment
of choice and have decreased the need for total gastrectomy. Initial doses of
omeprazole or lansoprazole should be in the range of 60 mg/d. Dosing can be
adjusted to achieve a BAO <10 meq/h (at the drug trough) in surgery-naive
patients and to <5 meq/h in individuals who have previously undergone an
acid-reducing operation. Although the somatostatin analogue has inhibitory
effects on gastrin release from receptor-bearing tumors and inhibits gastric <a href="" name="PG1760"></a>acid secretion to some extent, PPIs have the advantage of
reducing parietal cell activity to a greater degree.<o:p></o:p></div>
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