Transcript University of Maryland GI Grand Rounds

Community Health
Education Seminar
Diarrhea After Eating
The Argument for
Intermittent Maldigestion Condition
and not just
“Irritable Bowel Syndrome-Diarrhea”
March 22, 2011
M. E. Money, M.D., FACP
Clinical Associate Professor Department of Medicine
University of Maryland School of Medicine
Office
354 Mill Street
Hagerstown, MD
301-797-0210
IRRITABLE BOWEL
SYNDROME
Brief Overview
M. E. Money. M.D.
Definition of IBS
IBS is a functional bowel disorder in
which abdominal pain or discomfort is
associated with defecation or a change in
bowel habit. Bloating, distension, and
disordered defecation are commonly
associated features.
Irritable bowel syndrome: a global perspective. World
Gastroenterology Organizational Global Guideline. April 20, 2009
M. E. Money. M.D.
Diagnostic Criteria (Rome III)
• Onset of symptoms at least 6 months before
diagnosis
• Recurrent abdominal pain or discomfort for >3
days per month during the past 3 months
• At least two of the following features:
– Improvement with defecation
– Association with a change in frequency of stool
– Association with a change in stool form
NB: What precedes the symptoms is not included.
WGO Practice Guidelines Irritable bowel syndrome 2009
M. E. Money. M.D.
Sub Types of IBS
IBS-Constipation
32%
IBS-Diarrhea
33%
IBS-diarrhea and constipation 35%
Executive Summary: IBS in Women: The Unmet Needs. Society for
Women’s Health Research. 2003
M. E. Money. M.D.
Mainstream concepts about IBS






Exact cause of irritable bowel syndrome not
known.
Multiple factors thought to contribute to etiology.
To date an 'IBS gene' has not been identified.
The concept of IBS as a diagnosis of exclusion is
“not acceptable any more”.
The treatment of IBS is targeted at symptom relief.
Cognitive behavioral therapy is very beneficial.
M. E. Money. M.D.
Predisposing, and precipitating factors
for irritable bowel syndrome
Predisposing factors
• Genetic predisposition
• Early life experiences
• Intergenerational
transmission of illness
behavior
• Gender
M. E. Money. M.D.
Precipitating Factors
• Acute and chronic stress
(life events)
• History of abuse
• Infection and
inflammation
• Bacterial flora and small
bowel bacterial
overgrowth
• Intestinal gas and motility
Perpetuating factors for irritable
bowel syndrome
• Maladaptive coping
• Poor social support
• Psychological co-morbidity
–
–
–
–
Somatization disorder
Depression
Anxiety
Panic Disorder
Gastrointestinal Disorders: Irritable Bowel Syndrome. Journal of
Clinical Outcomes Volume 1 (4). 2007
M. E. Money. M.D.
Irritable bowel syndrome impact
•
•
•
•
•
Estimated: 15 Million people in the U.S.
Prevalence 10-20% of adults
$2 Billion in direct annual costs
$20 Billion in indirect annual costs
Estimated only 1/3 patients seek medical
attention for condition.
Laudanum, U. Irritable Bowel Syndrome. Advanced Studies in Medicine. Vol.
4, No. 3. March 2004. Pages 128-134.
Executive Summary: IBS in Women: The Unmet Needs. Society for Women’s
Health Research.2003.
M. E. Money. M.D.
Mainstream treatment options for
IBS-Diarrhea
• Antidepressants
• Anticholinergics
(Bentyl, Levsin, etc)
• Bulking agents
(metamucil, etc)
• Chinese Herbal
therapies
• Cholestyramine
M. E. Money. M.D.
• Antispasmodics
• Lactase
supplementation
• Antibiotics
• Serotonin modulators
• Antidiarrheals drugs
(Lomotil, etc)
• Deodorized tincture of
opium
Treatment options conclusion in
Prescire International 2009
“There is currently no way of radically modifying the
natural course of recurrent irritable bowel syndrome”
• Patients frequently complain of occasional bowel
movement disorders, associated with abdominal pain or
discomfort, but they are rarely due to an underlying organ
involvement. Even when patients have recurrent
symptoms, serious disorders are no more frequent in these
patients than in the general population, unless other
manifestations, anemia, or an inflammatory syndrome is
also present;
Irritable bowel syndrome: a mild disorder; purely symptomatic treatment. Prescrire.Int.
18(100), 75-79. 2009
M. E. Money. M.D.
Accuracy of symptom-based criteria for
diagnosis of IBS in primary care1
Reviewed 25 primary diagnostic studies.
2 research questions:
Performance of symptom-based criteria in
excluding organic GI disease.
Performance of signs and symptoms in identifying
IBS
Conclusion: “organic disease cannot be accurately
excluded by symptom-based IBS criteria alone.”
1Jellema,
P. et al. Systematic review: accuracy of symptom-based criteria for diagnosis
of irritable bowel syndrome in primary care. Alimentary Pharmacology &
Therapeutics. 7-3-09. DOI: 10.1111/j.1365-2036
M. E. Money, MD
How did this research get
started?
In September 2001, one of my patients came in
“demanding” that I prescribe something to help with
her diarrhea that would occur after she ate out in
restaurants with her family By that time, I had given
pancreatic enzymes to 2 patients in my practice for
after meal diarrhea due to surgery on the pancreas
with good results and decided to give it to her as a
“clinical experiment.”
She returned 4 weeks later, reporting that “1 pill before
the meal worked just fine”, 4 made her constipated.
By Christmas, I had prescribed it to another 10
individuals and all but one had complete symptom
relief.
M. E. Money, M.D
How did this research get
started?
By Christmas, I had also researched the current
recommendations for IBS-D and had discovered
pancreatic enzymes were not mentioned. I had also
checked with 2 specialists to assure there was no
harm in using enzymes, and decided to do my own
study comparing pancreatic enzymes to placebos.
The study was approved by the Washington County
Review Board in January 2002 and the first patients
were enrolled in February.
It concluded in 2003. 49 patients enrolled, 10 dropped
out, and 25/39 who did participate “picked” the
enzymes as the effective agent.
M. E. Money. M.D
DOUBLE BLIND, PLACEBO CONTROLLED
TRIAL USING PANCREATIC ENZYMES
Effectiveness of PAncreatic EnZyme in Reduction
of IrritAble Bowel Syndrome (IBS)
Symptoms “PAZAS”
Hypothesis
• Symptoms of post prandial IBS-D are due to maldigestion
and/or malabsorption of certain foods, thus causing the
abdominal symptoms including diarrhea for some patients.
Approved by WCH IRB 2/01, completed 11/03
M. E. Money. M.D.
15
PAZAS Inclusion Criteria
Meet the Rome II Criteria
• Be at least 18 and willing to give written informed consent,
• Have onset of symptoms before the age of 50
• Have symptoms occurring postprandial greater than 90% of the time
within 3 hours of the trigger food/meal. Ideally should be able to
identify some of the foods/spices/ or types of meals that precipitate the
symptoms. (i.e. restaurant dining, Italian, Chinese, specific foods,
lactose based*).
• *Participants must have at least one other food/spice that causes
symptoms in addition to Lactose based foods.
• Be willing to comply with all of the study protocol.
• Have had a normal Colonoscopy or barium enema within the same time
period of current symptoms.
• Have had IBS postprandial symptoms for greater than 5 years.
M. E. Money. M.D.
16
Methodology
Study stages:
1. Patients consumed 6 trigger meals recording
symptoms (baseline)
2. Consumed same meals with blinded capsule.
3. Wash out period 2 weeks.
4. Consumed same meals with second blinded capsule.
5. Picked either drug 1 or 2 to use for another 25-50 meals.
6. Unblinded to patient only after patient completed study;
unblinded to staff at study conclusion.
M. E. Money. M.D.
17
Symptoms evaluated and scoring
SYMPTOM
POINTS POSSIBLE
Cramping
0-10
Bloating.
0-10
Borborygami (gurgling, noises, churning)
0-10
Nausea
0-10
Intensity of the urge to have a bowel movement
0-10
Other symptoms (sweating, chills, weakness)
0-10
Global pain intensity
0-10
Number of Bowel Movements after eating the meal
(1 point for each BM)
Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of
postprandial irritable bowel syndrome-diarrhoea. Money, ME; Walkowiak,J; Virgilio,C.; Talley, NJ;
Frontline Gastroenterology.2011;2:48–56.
M. E. Money. M.D.
Summary of results
Total number of patients enrolled in study:
Number of patients who dropped out:
Number of patients who selected Enzymes as the
“effective agent” after trying both capsules:
Number of patients who selected placebo as the
“effective agent”:
49
10
25
10
In an intention to treat analysis, overall, 30/49 (61%)
would have chosen enzymes (p=0.078)
Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase
for the treatment of postprandial irritable bowel syndrome-diarrhoea. Money,
ME; Walkowiak,J; Virgilio,C.; Talley, NJ; Frontline
Gastroenterology.2011;2:48–56.
M. E. Money. M.D.
Subset Analysis of Enzyme Patients
Preliminary Results I
7
Patient scored Severity of symptoms
0-10
6
5
4
Baseline
Placebo
Enzymes
3
2
1
0
Cramping
M. E. Money. M.D.
Bloating
Gurgling
Nausea
Subset Analysis of Enzyme
Patients Preliminary Results II
9
8
7
6
Baseline
Placebo
Enzyme
5
4
3
2
1
0
BM urge
M. E. Money. M.D.
BM #
Onset
Duration
Subset Analysis of Enzyme Patients
Preliminary Results III
25
20
15
Baseline
Placebo
Enzymes
10
5
0
Other sx
M. E. Money. M.D.
Pain
Stool pts
Lomotil pts
Quality of Life (QOL) survey
Patients were asked to score how each of 34
questions applied to their quality of life
before and at conclusion of study.
0-Not at all,
1-slightly,
2-moderately,
3-quite a bit,
4-a great deal, extremely.
Used with the permission of Dr. D. L. Patrick, University of
Washington.
M. E. Money. M.D.
Examples of QOL questions
• I feel helpless because of my bowel problems.
• I feel like I’m losing control of my life because of
my bowel problems.
• I feel depressed about my bowel problem.
• I feel isolated from others because of my bowel
problems.
• Long trips are difficult for me because of my
bowel problems.
• My bowel problems are affecting my closest
relationships.
M. E. Money. M.D.
QOL statistical analysis
Study enzyme subgroup
Statistical T-test Procedure “p” values comparing QOL
scores at baseline and end of study
Helpless
Losing control of life
Depressed
Worry
Avoid stressful situations
Affecting closest relationships
M. E. Money. M.D.
p <.0001
<.0001
.0002
<.0001
.0065
.0062
Effectiveness of pancreatic enzymes
A retrospective review was recently completed of all of the
patients in my practice who had the diagnosis of IBS
and had been treated by me from 2001-2010 to evaluate
the effectiveness of the enzymes.
278 patients had received a diagnosis of spastic colon or
IBS
– 134 excluded since they had been treated by
another practitioner
– 144 seen by me, and 104 had been offered PEZ
• 86/104 patients returned for follow-up,
and 82.5% (71) reported positive
improvement
M. E. Money. M.D.
Examples of Food Triggers Among
49 “users”
Food Trigger
#
%
Food Trigger
#
%
Mexican Food
36
74%
Green Peppers
18
37%
Cajun
33
67%
Oranges
16
33%
Iceberg Lettuce 27
55%
Onion
16
33%
Italian
27
55%
Broccoli
16
33%
Chinese
27
55%
Garlic
13
27%
Ice Cream
26
53%
Beans
13
27%
Milk
20
41%
Apples
13
27%
Corn
19
39%
Tomatoes
12
25%
M. E. Money. M.D.
27GI Grand Rounds
UMD
Example of new patient
• 43 yr female seen by me as a new patient 7/24/09
• History: Complains of intermittent increased loose
stools after meals for 11 yrs, sometimes at night if eats
late. She wonders if she has IBS. Symptoms may last
for weeks once it gets started, otherwise only when
eats out in restaurants. Worse with spicy foods,
onions, garlicky Italian meals and tomatoes.
• Exam entirely normal. 64” tall, 161#
• Chronic medical problems other than above: Asthma
• Current meds: Zyrtec, Advair Diskus, Ventolin inhaler
• Mother has similar digestion problem.
• Patient had never had a colonoscopy.
M. E. Money. M.D.
28
New patient continued
• Patient referred to gastroenterologist who wrote:
“Patient states she has cramping, watery diarrhea
alternating with constipation, up to 10x/day, mild in
nature…..symptoms are suggestive of IBS.”
• Investigation by gastroenterologist:
–
–
–
–
Colonoscopy negative
X-rays for the stomach and small intestine were normal
Blood tests for Celiac disease was normal
Biopsy of colon negative for pathology
• Treatment: Patient encouraged to try probiotics by
gastroenterologist.
M. E. Money. M.D.
New patient continued
Additional testing ordered by me:
• Stool for fat: SMALL amount (8/19/09)
• Fecal elastase-1: 487 (normal >200) (test for pancreatic
insufficiency)
• Patient seen 9/4 in office. Probiotics tried by patient but
did not prevent post restaurant dining diarrhea. I therefore
gave the patient some samples of prescription pancreatic
enzymes to try before restaurant meal or “triggers”. They
worked with the first meal!
• Current treatment: Pancreatic Enzymes before
“trigger” meals eliminates both the abdominal
pain and diarrhea.
M. E. Money. M.D.
Why do the enzymes work?
For the last 8 years, I have pursued trying to
figure out why the pancreatic enzymes
work. This presentation will focus on my
current hypothesis and why making the
diagnosis of “irritable bowel syndromediarrhea” may limit further research into
this condition.
M. E. Money. M.D.
Pancreatic Enzymes
• Composition:
Amylase, Lipases, Proteases, Co-lipases, other
enzymes
• Known Action
– Initiates digestion of carbohydrates, lipids and proteins
in the stomach
– Amylase potentiates the action disaccharidases by 1020x.
(Quezada-Calvillo, R. et al. Contribution of Mucosal MaltaseGlucoamylase Activities to Mouse Small Intestinal Starch αGlucogenesis. Journal of Nutrition. 137:1725-1733, 2007
M. E. Money. M.D.
UMD32
GI Grand Rounds
Sub types of IBS
IBS-Constipation
32%
IBS-Diarrhea
33%
IBS-diarrhea and constipation 35%
Executive Summary: IBS in Women: The Unmet Needs. Society for
Women’s Health Research. 2003
M. E. Money. M.D.
Incidence of diarrhea occurring after
eating
50% of patients suffering with the diarrhea or
mixed form of IBS related symptoms to
eating.
However, the current definition of IBS does not
encourage nor require the physician to inquire
about any precipitating factor such as the
condition occurring ONLY after eating.
M. E. Money. M.D.
Differential diagnosis for IBS
•
•
•
•
•
•
•
•
•
•
•
Celiac Sprue/gluten enteropathy
Lactose intolerance (inherited or 2nd to mucosal damage)
Inflammatory bowel disease
Colorectal carcinoma
Lymphocytic and collagenous colitis
Acute diarrhea due to protozoa or bacteria
Small-intestinal bacterial overgrowth (SIBO)
Diverticulitis
Endometriosis
Pelvic inflammatory disease
Ovarian cancer
• WGO Practice Guideline IBS 2009
M. E. Money. M.D.
What is missing from this
differential diagnosis?
1. Bile acid malabsorption diarrhea
2. Pancreatic insufficiency
3. Carbohydrate Malabsorption
– Alpha glucosidases (disaccharidases)
deficiencies (maladigestion of starches)
–
–
–
Congenital sucrase-isomaltase deficiency
Fructase deficiency
? Possible disaccharidase inhibition
M. E. Money. M.D.
Bile acid malabsorption
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Bile acid malabsorption can occur in patients with
or without an intact gall bladder
Bile acid malabsorption(BAM) may affect up to
30-50% of patients with chronic diarrhea
Can be treated with bile acid binding agents:
Welchol, Cholestyramine, Questran
Diagnosis by measurement of serum 7alphaC4
(not available for routine testing)
M. E. Money. M.D
Diarrhea predominant IBS (IBS-D):
fact or fiction


Dr. Saad Habba, gastroenterologist in NY,
analyzed all patients seen by him over the
last 8 yrs for “IBS-D”.
575 patients seen, only 303 patients
completed all of the studies. Of these 303
patients, 204 (68%) responded to bile acid
binding agents with resolution of diarrhea.
Diarrhea Predominant Irritable Bowel Syndrome-Diarrhea: Fact or
Fiction. Habba,S., Medical Hypotheses 76(2011) 97-99.
M. E. Money. M.D
Pancreatic insufficiency
Pancreatic insufficiency was found in 6.1%
(19/314) patients who had been diagnosed as
having IBS-D by the Rome Criteria. This was
determined by the measurement of the fecal
elastase-1 concentration in the stool. Patients
were then treated with pancreatic enzyme
supplements with a statistical improvement in
stool frequency, consistency, and abdominal pain.
Some Patient With Irritable Bowel Syndrome May Have Exocrine
Pancreatic Insufficiency. Leeds, J et al, Clinical Gastroenterology and
Hepatology 2010; 8:433-438.
M. E. Money. M.D
Carbohydrate malabsorption
“Carbohydrate malabsorption and intolerance is
suggested by the patient’s clinical history. The
relation of symptoms to feeding and the
occurrence of remission while fasting are crucial
to the history. In older children and adults the
symptoms can resemble those of dyspepsia or
irritable bowel syndrome (IBS)…The diagnosis of
functional bowel disease usually is made without
evaluation of carbohydrate digestion… symptoms
from IBS and carbohydrate intolerance can be
confused easily”.
Disaccharide Digestion: Clinical and Molecular Aspects. Robayo-Torres, C. et
al; Clinical Gastroenterology and Hepatology. 2006;4:276-287
M. E. Money. M.D.
1° Lactose malabsorption
• Frequency: Isolated deficiency in 16-24% of patients with
IBS and in 12% of patients with functional bowel
complaints. (Autosomal recessive, C>T 13910, Intron 13
or MCMG 6 gene.)
• Is usually combined with fructose, sorbitol, glucoamylase,
sucrase, and maltase deficiency among patients with
functional GI complaints.
• Disaccharide Digestion: Clinical and Molecular Aspects. RobayoTorres, C. et al; Clinical Gastroenterology and Hepatology.
2006;4:276-287
M. E. Money. M.D.
Carbohydrate malabsorption
syndromes
1° Lactose Maldigestion
• Due to Lactase deficiency,
(a beta-glucosidase)
• Symptoms after the
ingestion of milk
products:
–
–
–
–
Abdominal pain
Cramps
Urgent diarrhea
Time of onset: variable
depending upon quantity
and sensitivity of
patient
M. E. Money. M.D.
Disaccharide Maldigestion
• Due to alphaglucosidase(s) deficiency
• Symptoms after the
ingestion of carbohydrates
(lettuce, beans, corn, etc)
–
–
–
–
Abdominal pain
Cramps
Urgent diarrhea
Time of onset: variable
depending upon quantity
and sensitivity of patient
Digestion of starches
Initial hydrolysis of starches begin
with the action of amylase from the
saliva. 95% of starches are not
broken down until they reach the
small intestine where pancreatic
amylase breaks the starch into
smaller units: maltose, maltotriose,
and limits dextran size.
M. E. Money. M.D.
Digestion of disaccharides:
alpha-glucosidases
Further hydrolysis of carbohydrates
after amylase involves the brush
border disaccharidases also known as
“alpha-glucosidases:”
•Maltase
•Isomaltase
•Sucrase
•Trehalase
•Gluco-amylase
M. E. Money. M.D.
Alpha-glucosidase inhibition
Drugs: Acarbose ( a diabetic medication to reduce
absorption of carbohydrates by preventing absorption).
Side effect: >30% patients experience diarrhea
Spices and foods:
>1000 known to affect a-glucosidases
Examples:
Clove extract
Quercetin (found in onions, 5x more potent
than acarbose)
Some spices >1000x more potent than acarbose
(verbal report Dr. Buford Nichols)
Bacterial Overgrowth
M. E. Money. M.D.
Sucrase-isomaltase deficiency in
adults and varied symptoms
Sucrose-Isomaltose Malabsorption in an Adult Woman
(Sonntag, W. M. et al, 1964, Gastroenterology 47:18.)
20 Greenlandic Eskimos found to have sucrose malabsorption
8 adults, only 1 with symptoms
(McNair, et al. 1972, Sucrose malabsorption in Greenland, Br. Med J.
2:19.)
Ringrose (1980): 13 adult patients with bx proven SI def.
5 had persistant or intermittent symptoms since childhood
2 symptoms in childhood, disappeared again until 20; 40.
3 symptoms first appeared in first or second decade.
(1980, Dig. Dis. Sci. 25:384)
Gudmand-Hayer (1985) Studied 31 children, and 12 adults hospitalized in
Greenland. Of the 12 adults, 8 had a “long-lasting history of chronic
diarrhea and abdominal complaints”.
M. E. Money. M.D.
Sucrase-isomaltase and glucoamylase
deficiency in children
1-2% of children with severe diarrhea from birth are
found to have an inherited sucrase-isomaltase
disaccarhidase deficiency
Recent research by Dr. Buford Nichols (Baylor College,
Houston, Texas) in collaboration with Dr. Susan Baker
( Woman and Children Hospital of Buffalo, NY ) have
found 26% of children with digestion symptoms have
difficulty digesting starch due to a deficiency of
glucoamylase.
M. E. Money. M.D.
More support for maldigestion as
possible cause of diarrhea
A very low-carbohydrate diet improves symptoms
and quality of life in IBS-D patients. 2009
Prospective Study
17 enrolled with moderate to severe IBS-D
Initially had 2 weeks of standard diet, then 4 weeks of
very low (20gm carbohydrate/day).
13 completed the study. 10 (77%) reported adequate relief
for all 4 weeks on the low carb diet; stool number
decreased, QOL improved, and decrease in pain.
Clin Gastroenterol Hepatol. Austin, GL; Dalton, CB; et.al. 2009 June;
7(6) 706-708.el.doi:10.10167/j.cgh.2009.02.023
M. E. Money. M.D.
More support for maldigestion as
possible cause of diarrhea
In Indonesia, biopsies taken from the small intestine
were examined for concentration of Lactase,
Sucrase, and Maltase from 13 patients with
chronic diarrhea, and compared to biopsies from
34 patients with “dyspepsia”.
Results: All of enzyme concentrations from the
patients with chronic diarrhea were statistically
lower than those with dypepsia.
Examination of small bowel enzymes in chronic diarrhea. J
Gastroenterol Hepatol. Simadibrata, m., et al.18(1): 53-6.
M. E. Money. M.D.
Working hypothesis
Diarrhea occurring after meals may
actually be a subclinical form of
inherited or acquired maldigestion,
possibly related to a bile acid
malabsorption or a mild deficiency,
relative ineffectiveness or suppression
of one or more enzymes: amylase,
lipase, the disaccharidases, or others.
M. E. Money. M.D.
Summary
• The current Rome Criteria may be limiting
appropriate research and treatment for a subset of
IBS-D patients who recognize the direct
association of symptoms with meals or triggering
foods. The relationship to meals should be sought
in obtaining the history from patients.
• A high percentage of these patients probably have a
subclinical form of maldigestion which may be
substantially improved by the use of enzymes or
bile acid binding agents when taken immediately
before eating the “triggering meal.”
M. E. Money. M.D.
Proposed new diagnosis
Intermittent Maldigestion Condition
(IMC)
Symptoms of increased bowel movement(s),
occurring after eating a “specific meal type” or
“trigger” according to the patient, which may be
altered in form or consistency. Symptoms may
occur immediately after eating or several hours
later and do not have to occur daily.
M. E. Money. M.D.
Potential treatment options for
patients with diarrhea after meals
Over the counter agents:
Fiber capsules (which absorbs extra liquids)
Calcium (which slows down the motility naturally),
Enzyme supplement: Essential Enzymes 500 mg (by Source
Natural), an over the counter supplement (1-3) before eating any
“trigger meal” or daily as needed.
Prescription medications from a physician:
Pancreatic enzymes: examples: ZenPep 20,000 lipase, Creon 24
(1-3capsules) before eating any “trigger meal” or daily as
needed.
Bile acid binding drugs: Questran 1-2 packages/day; Welchol
625 mg (1-3) before eating any trigger meal or daily as needed.
M. E. Money. M.D.
Future research questions
• What is the incidence of sucrase-isomaltase
deficieny in adults with diarrhea after eating?
• Do over the counter enzyme supplements work as
well as the prescription pancreatic enzymes?
• How/why do certain food items cause the
diarrhea?
• Do the foods suppress the disaccharidase action or
amylase from the pancreas or speed up the
motility?
• Are there specific genes that are predispose a
person to having this problem?
M. E. Money. M.D.
Funding opportunities
Donations are welcomed to help fund this important
research and can be made to the
RESEARCH FUND
at the
Meritus Healthcare Foundation
HUB Plaza 1101 Opal Court Suite 301,
Hagerstown, MD 21740
301-790-8631 | TDD: 1-800-735-2258
[email protected]
M. E. Money. M.D.