TITLE: Confirmation of Eradication of Helicobacter pylori and Subsequent Effects on Peptic

Ulcer Reoccurrence
DATE: March 10, 2014
PRINCIPLE INVESTIGATORS:
David Y. Graham Ginger M. Lew
123 Daisy Road, 3672 Apple Lane,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 123-4567 (657) 365-8627
dgraham@fullerton.edu glew@fullerton.edu

Peter D. Klein Dolores G. Evans
75436 Daisy Road, 6426 Texas Street,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 555-2625 (657) 625-2625
glew@fullerton.edu dgevans@fullerton.edu

Doyle J. Evans Zahid A. Saeed
764 Apple Lane, 557 Misty Drive,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 124-6355 (657) 625-4665
djevans@fullerton.edu asaeed@fullerton.edu

Hoda M. Malaty Jennifer L. Spencer
769 New York Street, 456 Plant Lane,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 276-7655 (657) 755-5757
hmalaty@fullerton.edu jspencer@fullerton.edu



ABSTRACT:
To study connections between treatment of Helicobacter pylori and ulcer reoccurrence,
two groups of patients who have received a single drug or triple drug treatment for gastric or
duodenal ulcers associated with H. pylori will be evaluated. The follow-up studies will take place
at a single Veterans Affairs hospital to easily monitor patients and have access to patient
records. It is hypothesized that there will be a high correlation between full eradication of H.
pylori infection and reoccurrence of gastric and duodenal ulcers. This follow-up study will
employ endoscopic techniques for the diagnosis of ulcers as well as detection of H. pylori
bacteria through enzyme-linked immunosorbent assays (ELISA), cell culture and histological
analyses. Study outcomes could provide insight into the most effective drug strategies for
treatment and prevention of ulcers as well as significant contributions to the scientific
community, economic viability and national health.
Keywords: H. pylori, ulcers, reoccurrence, gastric, duodenal

PROJECT DESRIPTION:
Objectives of Proposed Research: The main objective of the proposed research is to
fill a gap in scientific knowledge by substantiating a causal connection between infections of the
bacteria, Helicobacter pylori, and the reoccurrence of both gastric and duodenal ulcers.
Previous studies have only shown a connection between the eradication of H. pylori infection
and general healing of gastritis. These studies have confirmed the decrease in reoccurrence of
duodenal ulcers in association with the eradication of H. pylori, but have not been able to extend
those findings to the reoccurrence of other types of peptic ulcers. Additionally, more thorough
studies into this connection are necessary due to the lack of controls or blinding groups in
previous studies. By studying how various treatments of H. pylori infection effect ulcers, this
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Comment: This is kind of wordy. I would try
rephrasing. May need to change sentence structure.
Deleted: the
Deleted: in general
Deleted: a
research aims to substantiate total H. pylori eradication as a way to prevent long-term
reoccurrence of duodenal and gastric ulcers.
Significance: By studying how the eradication of H. pylori infections effects the
reoccurrence of gastric and duodenal ulcers, this research would be significant across various
realms. The overall decrease of ulcer reoccurrence among patients in the general population
would be of great humanitarian significance. It would greatly lessen the number of patients
negatively affected by gastric and duodenal ulcers. Additionally, deciphering the connection
between H. pylori and the reoccurrence of ulcers would be significant from an economic
perspective as well. The people most prone to developing ulcers are of prime age to be a
contributing member of the workforce. Determining which treatments of H. pylori lead to fewer
reoccurrences of infection and ulcers will result in a more healthy and vibrant national
workforce.
Long-term Goals: Long-term implications of this research could aid in determining
which therapy types are best for total eradication of H. pylori infection. Additionally, based on
the full eradication of the bacteria, the incidence rate of patients with reoccurring peptic ulcers
would be lowered. Lessening the number of people that have to struggle with reoccurring ulcers
and receive continued or ongoing treatment will increase patients quality of future life. A second
long-term goal of this research would be to determine the best possible treatment for the
specific type and degree of gastritis. As ulcers can range in level from mild to extremely severe,
knowing how to best treat each incident could help prevent the reoccurrence of ulcers on the
front end of treatment. Additionally, antibiotic resistant bacterial infections are becoming more
prevalent through public misuse and unnecessary prescription of antibiotics. Understanding
which types of treatments, are necessary to treat various severities of ulcers, and H. pylori will
aid in limiting the formation of strains of antibiotic resistant H. pylori as well as protect the
efficacy of antibiotics against H. pylori infections. Additional benefits of a wider knowledge base
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Deleted: Through
Deleted: a
Deleted: incidence of
Comment: Pretty vague, can you be more specific.
Comment: Remember the old to new rule.

The previous sentence goes decreasing ulcer >>
better for humans. And this one starts off by going
back to decreasing ulcers. I would flip the order of
the previous sentence and it would flow better
between these sentences.

Another option would be to find a way to combine
the two sentences.
Comment: This makes it sound like a puzzle. You
may want to say understanding or investigating
depending on what direction you were going with.
Comment: I suggest adding a transition between
these sentences. It would make it seem less abrupt to
start talking about the age topic
Comment: Old to new rule again. Check previous
sentence.
Comment: This is wordy. I would try to shorten it
and be more concise if possible. Think about active
voice.
Deleted: By l
Deleted: ,
Deleted: the higher quality of life patients will
have in the future
Comment: Of treatments of what? the bacteria or
the ulcers?
Comment: How will it? This part is confusing
Comment: I would break this sentence into two.
of drug therapies for peptic ulcers include vast economic benefits for the pharmaceutical
industry.
Relation to Present State of Knowledge in the Field: Several studies have shown that
the H. pylori infection is a causal agent of gastritis. Additionally, H. pylori has been authenticated
as a strong predictor of peptic ulcer reoccurrence. However, adequate studies addressing the
reoccurrence of various types of peptic ulcers as a result of insufficient eradication of H. pylori
infections have not been performed. As previously mentioned, the incidence of duodenal ulcer
reoccurrence has been substantiated, but the of gastric ulcers have not been satisfactorily
studied. Targeting the overarching issue of total eradication of H. pylori and reoccurrence of
both duodenal and gastric ulcers would lead to significant contributions to the body of
knowledge. In addition to extending the body of knowledge to include reoccurrence of gastric
ulcers, this research could further substantiate a role for H. pylori infection in the reoccurrence
of ulcers in general. As adequate controls were not been used in previous studies, this
connection could be reevaluated through this research.
General Plan of Work: In order to substantiate the connection between H. pylori
eradication and the reoccurrence of duodenal and gastric ulcers, a long-term follow up study on
patients previously treated for peptic ulcers will be conducted. The study will take place at a
Veterans Affairs hospital and follow two groups of patients who had received different
treatments for either gastric or duodenal ulcers caused by H. pylori infections. The various
treatment groups include patients with gastric ulcers treated with either rantitidine alone or
rantitidine plus triple therapy (bismuth subsalicylate, tetracycline hydrochloride and
metronidazole) and duodenal ulcers treated with either rantitidine alone or rantitidine plus triple
therapy (bismuth subsalicylate, tetracycline hydrochloride and metronidazole). Previously
treated patients will be assessed for symptoms of ulcer reoccurrence up to two years after their
initial treatments beginning with one month after treatment and up to every three months for the
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Comment: I think you are missing a word. Maybe
connections
Comment: This is a perfect old to new !:)
duration of the trials. Should symptoms return, patients will be monitored for the reoccurrence of
ulcers through endoscopies performed by blinded technicians who will remain unaware of the
patients treatment group or previous ulcer status. Further assessment for H. pylori infection will
be done through the C-urea breath test, enzyme-linked immunosorbent assay (ELISA), bacterial
cultures and histological analyses. Statistical analysis and predictive models of peptic ulcer
reoccurrence will be calculated using the lifetable method and assessed by chi-squared test or
Fisher exact test.
Broader Impacts of Research and Future Work: The scope of medicinal, economical
and overall beneficial knowledge that this research could provide is immense. The broader
impacts of this research include developing the best therapies for types and severity of peptic
ulcers and ultimately reducing the incidence of gastric and duodenal ulcer reoccurrence.
Additionally, developing simpler protocols and improved therapies for the treatment of peptic
ulcers and H. pylori infection would be beneficial for patients, clinicians and industry alike. This
research could also aid in future directions of research, such as determining what the main risk
factors are for H. pylori infections and peptic ulcer reoccurrence. Being aware of the risk factors
involved could help to ultimately implement better lifestyle choices for both patients prone to H.
pylori infection and ulcer reoccurrence as well as the general public.

REFERENCES CITED:
1. Sontag SJ. Current status of maintenance therapy in peptic ulcer disease. Am J
Gastroenterol. 1988;83:607-17.

2. Coghlan JG, Gilligan D, Humphries H, McKenna D, Dooley C, Sweeney E, et al.
Campylobacter pylori and recurrence of duodenal ulcersa 12-month follow-up study. Lancet.
1987;2:1109-11.

3. Lambert JR, Borromeo M, Korman MG, Hansky J, Eaves ER. Effect of colloidal bismuth (De-
Nol) on healing and relapse of duodenal ulcers-role of Campylobacter pyloridis [Abstract].
Gastroenterology. 1987;92:1489.

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Comment: I stopped here
4. Marshall BJ, Goodwin CS, Warren JR, Murray R, Blincow ED, Blackbourn SJ, et al.
Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter
pylori. Lancet. 1988;2:1437-42.

5. Rauws EA, lytgat GN. Cure of duodenal ulcer associated with eradication of Heticobacter
pylori. Lancet. 1990;335:1233-5.

6. George LL, Borody TJ, Andrews P, Devine M, Moore-Jones D, Walton M, et al. Cure of
duodenal ulcer after eradication of Helicobacter pylori. Med J Aust. 1990;153:145-9.

7. Graham DY, Lew GM, Evans DG, Evans DJ Jr, Klein PD. Effect of triple therapy (antibiotics
plus bismuth) on duodenal ulcer healing with ranitidine. A randomized controlled trial. Ann Intern
Med. 1991;115:266-9.

8. Graham DY, Klein PD, Evans DJ Jr., Evans DG, Alpert LC, Opekun AR, et al. Campylobacter
pylori detected noninvasively by the 13C-urea breath test. Lancet. 1987;1:1174-7.

9. Klein PD, Graham DY. Campylobacter pylori detection by the 13C-urea breath test. In:
Campylobacter pylori and Gastroduodenal Disease. Rathbone BJ, Heatley V, eds. Blackwell
Scientific Publications, Oxford. 1989;94-106.

10. Evans DJ Jr, Evans DG, Graham DY, Klein PD. A sensitive and specific serologic test for
detection of Campylobacter pylori infection. Gastroenterology. 1989;96:1004-8.

11. Rauws EA, Langenberg W, Houthoff HJ, Zanen HC, Tytgat GN. Campylobacter pytoridis-
associated chronic active antral gastritis: a prospective study of its prevalence and the effects of
antibacterial and antiulcer treatment. Gastroenterology. 1988;94:33-40.

12. Van Deventer GM, Elashoff JD, Reedy TJ, Schneidman D, Walsh JH. A randomized study
of maintenance therapy with ranitidine to prevent the recurrence of duodenal ulcer. N Engl J
Med. 1989;320:1113-9.

13. Graham DY, Borsch GM. The who's and when's of therapy for Helicobacter pylori [Editorial].
Am J Gastroenterol. 1990;85:1552-5.

14. Graham DY, Lew GM, Malaty HM, Evans DG, Evans DJ Jr, Klein PD, et al. Factors
influencing the eradication of Heticobacter pylori with triple therapy. Gastroenterology.
1992;102:493-6.


BIOGRAPHICAL SKETCH:
My educational background is in biological science, specifically utilizing molecular and
microbiological techniques. My experience with biology has been developed through
coursework such as advances in molecular techniques, immunology, virology and microbiology.
Additionally, I have previous experience working with defense responses of tobacco plant
species and developing effective treatments against the Acinetobacter baumannii bacterial
infection. My intellectual and research interests include prevention and treatment strategies for
infectious diseases. Currently, I am a junior and will receive a Bachelors of Science degree
from California State University, Fullerton in May 2015.