Appendix D-1 – Research Programs and Studies at UNC Center for Functional

GI and Motility Disorders

Rese

arch

Dom

ain

Fund

ing

Sour

ces

Inve

stig

ator

/ Se

lect

ed P

eer R

evie

w

Publ

icat

ions

Find

ings

from

Res

earc

h Co

mm

ents

Basic

and

Clin

ical

Psy

chop

hysio

logy

Psyc

hoph

ysio

logy

of

IBS

NIH

K

anaz

awa,

Whi

tehe

ad,

Dro

ssm

an 1

Cas

e-co

ntro

l stu

dy sh

owin

g th

at c

olon

ic

mot

ility

and

pai

n se

nsiti

vity

mak

e in

depe

nden

t co

ntri

butio

ns to

GI s

ympt

oms i

n IB

S

Smal

l Int

estin

al

Bact

eria

l O

verg

row

th in

IBS

NIH

G

rove

r, W

hite

head

, D

ross

man

2 C

ase-

cont

rol s

tudy

show

ing

that

smal

l in

test

inal

bac

teri

al o

verg

row

th is

not

sig

nifi c

antly

ass

ocia

ted

with

IBS,

but

met

hane

pr

oduc

tion

is as

soci

ated

with

con

stip

atio

n

Gen

etic

s of I

BS

NIH

Le

vy &

Whi

tehe

ad 3

Twin

stud

y sh

owin

g gr

eate

r con

cord

ance

for

IBS

in m

onoz

ygot

ic tw

ins;

how

ever

, soc

ial

lear

ning

had

com

para

ble

eff e

ct o

n et

iolo

gy

Ong

oing

stud

ies s

eek

to id

entif

y ge

netic

pol

ymor

phism

s ass

ocia

ted

with

IBS.

Vis

cera

l H

yper

sens

itivi

ty

NIH

D

orn/

Whi

tehe

ad/

Dro

ssm

an 4

Incr

ease

d co

loni

c se

nsiti

vity

in IB

S is

stro

ngly

in

fl uen

ced

by a

psy

chol

ogic

al te

nden

cy to

re

port

pai

n an

d ur

ge ra

ther

than

incr

ease

d ne

uros

enso

ry se

nsiti

vity

.

Epid

emio

logi

cal

U.S

. Hou

seho

lder

Ph

arm

aceu

tical

D

ross

man

/Whi

tehe

ad 5

Surv

ey o

f 5,0

00 U

.S. h

ouse

hold

ers t

hat

dete

rmin

ed n

atio

nal p

reva

lenc

e of

func

tiona

l G

I dis

orde

rs, I

BS w

as fo

und

in 1

1.2 %

Firs

t nat

iona

l sur

vey

of F

GID

s us

ing

Rom

e C

riter

ia.

UN

C-I

FFG

D S

tudy

Fo

unda

tion

Dro

ssm

an/N

orto

n 6 In

tern

atio

nal i

nter

net s

urve

y of

IBS:

1. P

atie

nts

with

IBS

who

use

Inte

rnet

hav

e hi

gh

prop

ortio

n of

mod

erat

e to

seve

re IB

S; 2

. Fa

ctor

s ass

ocia

ted

with

seve

rity

are

mul

tiple

; 3.

Patie

nts a

re w

illin

g to

take

incr

ease

d ri

sks t

o re

ceiv

e tr

eatm

ents

; 4. Th

ere

is d

issat

isfac

tion

and

an u

nmet

nee

d fo

r pro

per c

are.

Larg

e In

tern

et su

rvey

.

Hea

lthca

re C

osts

fo

r FG

IDs

Phar

mac

eutic

al

Nyr

op &

Whi

tehe

ad 7 /

Levy

& W

hite

head

8 D

irect

hea

lth c

are

cost

s for

IBS,

chr

onic

co

nstip

atio

n, fu

nctio

nal d

iarr

hea,

and

fu

nctio

nal a

bdom

inal

pai

n ar

e hi

gh, b

ut e

xces

s co

sts a

re p

rim

arily

for c

omor

bid

cond

ition

s.

Add

ition

al c

ost s

tudi

es o

n fe

cal

inco

ntin

ence

com

plet

ed a

nd

unde

r rev

iew.

Cha

ract

eriz

ing

Usu

al M

edic

al C

are

for I

BS

Phar

mac

eutic

al,

NIH

W

hite

head

, Pal

sson

, D

ross

man

9 O

bser

vatio

nal s

tudy

of l

arge

HM

O sh

ows t

hat

the

mos

t com

mon

trea

tmen

ts fo

r IBS

are

di

etar

y ad

vice

and

life

styl

e m

odifi

catio

n ra

ther

th

an d

rugs

, and

pat

ient

s hav

e m

ore

confi

den

ce

in th

is ad

vice

than

in d

rugs

.

A st

udy

of u

sual

med

ical

car

e fo

r ch

roni

c co

nstip

atio

n is

unde

r re

view

.

Epid

emio

logy

of

Feca

l Inc

ontin

ence

N

IH

Whi

tehe

ad 10

–12

NH

AN

ES st

udy

show

ing

prev

alen

ce a

nd ri

sk

fact

ors f

or fe

cal i

ncon

tinen

ce in

the

U.S

. no

n-in

stitu

tiona

lized

pop

ulat

ion.

Feca

l Inc

ontin

ence

Fo

llow

ing

Obs

tetr

ical

Inju

ry

NIH

W

hite

head

13, 1

4 C

ase-

cont

rol s

tudy

show

ing

that

the

odds

of

feca

l inc

ontin

ence

are

two–

thre

efol

d gr

eate

r in

wom

en w

ith a

reco

gniz

ed sp

hinc

ter l

acer

atio

n,

and

risk

is si

gnifi

cant

ly a

ff ect

ed b

y ag

e at

de

liver

y, se

verit

y of

tear

, Cau

casia

n ra

ce, a

nd

grea

ter b

ody

mas

s ind

ex.

(Con

tinue

d)

Rese

arch

Dom

ain

Fund

ing

Sour

ces

Inve

stig

ator

/ Se

lect

ed P

eer R

evie

w

Publ

icat

ions

Find

ings

from

Res

earc

h Co

mm

ents

Psyc

hoso

cial

, Clin

ical

Ass

essm

ent a

nd O

utco

mes

Rese

arch

In

stru

men

t D

evel

opm

ent

NIH

, CC

FA,

UN

C C

ente

r D

ross

man

– F

BDSI

15

Dro

ssm

an R

FIPC

16

Lese

rman

– A

buse

Se

verit

y 17

Dro

ssm

an/P

atri

ck

IBS-

QO

L 18-2

0

Dev

elop

ed a

nd st

anda

rdiz

ed re

sear

ch

inst

rum

ents

for f

unct

iona

l bow

el se

verit

y (F

GD

SI),

IBD

con

cern

s (RF

IPC

), ab

use

seve

rity,

and

HRQ

OL

in IB

S

IBS-

QO

L tr

ansla

ted

into

18

lang

uage

s and

is ra

ted

as b

est

HRQ

OL

inst

rum

ent f

or IB

S

Psyc

hoso

cial

and

A

buse

Out

com

es

NIH

D

ross

man

/Les

erm

an

17, 2

1, 2

2 Ri

ngel

/Whi

tehe

ad/

Dro

ssm

an 23

, 24

1. A

buse

hist

ory

is co

mm

on a

mon

g w

omen

in

GI p

ract

ice;

2. S

ever

e ab

use

foun

d in

hig

her

freq

uenc

y in

FG

IDs;

and

3. a

buse

hist

ory

pred

icts

poo

rer h

ealth

out

com

es. 4

. Rec

tal p

ain

thre

shol

ds a

re h

ighe

r in

wom

en w

ith IB

S an

d ab

use

hist

ory.

Firs

t to

syst

emat

ical

ly re

port

the

eff e

cts o

f abu

se in

a n

on-

psyc

hiat

ric

(i.e.

, med

ical

) po

pula

tion.

Com

orbi

dity

of I

BS

with

Som

atic

and

Ps

ychi

atri

c D

isor

ders

NIH

W

hite

head

25 / P

alss

on 26

C

ase-

cont

rol s

tudy

show

ing

exce

ss c

omor

bidi

ty

in IB

S is

rela

ted

to sy

mpt

om a

mpl

ifi ca

tion

and

low

thre

shol

d fo

r con

sulti

ng p

hysic

ian.

Team

has

also

syst

emat

ical

ly

revi

ewed

com

orbi

dity

lite

ratu

re.

Cop

ing

and

Seve

rity

NIH

D

ross

man

27, 2

8 1.

Mal

adap

tive

copi

ng (c

atas

trop

hizi

ng) i

s as

soci

ated

with

poo

rer h

ealth

out

com

es; 2

. Pa

tient

s with

mor

e se

vere

IBS

have

mal

adap

tive

copi

ng.

Firs

t to

repo

rt e

ff ect

s of c

opin

g on

cl

nica

l out

com

es in

GI p

opul

atio

n.

Brai

n Im

agin

g C

ente

r D

ross

man

/Rin

gel 29

-31

1. P

atie

nts w

ith a

buse

hist

ory

have

hig

her p

ain

resp

onse

s to

rect

al d

isten

sion

that

cor

rela

tes

with

incr

ease

d ac

tivat

ion

of d

orsa

l AC

C a

nd

decr

ease

d ac

tivat

ion

of sA

CC

; 2. A

CC

ac

tivat

ion

impr

oves

with

trea

tmen

t and

sy

mpt

om re

solu

tion.

Evid

ence

for a

med

iatin

g eff

ect

of

stre

ss (a

buse

) with

AC

C a

nd p

ain

– pr

ovid

es a

mec

hani

sm fo

r as

soci

atio

n of

stre

ss w

ith in

crea

sed

pain

.

Rom

e C

riter

ia

Foun

datio

n D

orn/

Dro

ssm

an 32

Ro

me

II a

nd R

ome

III c

riter

ia d

efi n

e a

simila

r po

pula

tion

with

IBS

Alte

rnat

ors a

nd

Stoo

l Pat

tern

s (D

oug)

NIH

, Ph

arm

aceu

tical

D

ross

man

33, 3

4 1.

IBS-

C a

nd IB

S-M

are

sim

ilar i

n st

ool

patte

rns a

nd p

ain

over

tim

e; 2

. Alte

rnat

or

defi n

ed a

s sw

itch

betw

een

IBS-

C a

nd IB

S-D

ov

er o

ne y

ear (

20 %

); 3.

Pai

nful

con

stip

atio

n as

soci

ated

with

poo

rer h

ealth

stat

us. t

han

less

pa

infu

l con

stip

atio

n

One

-yea

r pro

spec

tive

asse

ssm

ent.

Ecol

ogic

al

Mom

enta

ry

Ass

essm

ent

Phar

mac

eutic

al

Wei

nlan

d/D

ross

man

O

ngoi

ng

Will

add

ress

the

imm

edia

te

asso

ciat

ion

of p

ain

and

stre

ss w

ith

bow

el h

abit

usin

g PD

A.

IBS

Dev

elop

men

t Bi

natio

nal

Isra

el-U

SA

Scie

nce

Foun

datio

n

Sper

ber/

Dro

ssm

an 35

, 36

1. 1

7 % o

f pat

ient

s dev

elop

ed a

bdom

inal

/pel

vic

pain

with

in o

ne y

ear a

ft er s

urge

ry c

ompa

red

to

3 % in

con

trol

s; 2.

Pai

n w

as p

redi

cted

by

psyc

hoso

cial

rath

er th

an c

linic

al fa

ctor

s; 3.

C

onst

ipat

ion

does

not

dev

elop

aft e

r pel

vic

surg

ery

mor

e th

an in

con

trol

s.

Firs

t pro

spec

tive

stud

y to

show

de

velo

pmen

t of p

ain

sym

ptom

s/IB

S aft

er s

urge

ry in

a p

ain

naïv

e po

pula

tion.

(Con

tinue

d)

Rese

arch

Dom

ain

Fund

ing

Sour

ces

Inve

stig

ator

/ Se

lect

ed P

eer R

evie

w

Publ

icat

ions

Find

ings

from

Res

earc

h Co

mm

ents

Soci

al L

earn

ing

in

the

Etio

logy

of I

BS

NIH

Le

vy &

Whi

tehe

ad 37

, 38

Two

larg

e ca

se-c

ontr

ol st

udie

s of t

he c

hild

ren

of w

omen

with

IBS

show

a h

ighe

r inc

iden

ce o

f G

I sym

ptom

s in

child

ren

and

supp

ort a

soci

al

lear

ning

hyp

othe

sis.

Ran

dom

ized

con

trol

led

tria

ls of

tr

eatm

ent b

ased

on

this

wor

k ar

e un

derw

ay in

chi

ldre

n w

ith

func

tiona

l abd

omin

al p

ain

and

child

ren

with

IBD

.

Out

com

e A

sses

smen

t in

IBS

Clin

ical

Tri

als

Phar

mac

eutic

al,

NIH

W

hite

head

39

Obs

erva

tiona

l stu

dy sh

owin

g th

at th

e gl

obal

ou

tcom

e m

easu

re “s

atisf

acto

ry re

lief”

is

conf

ound

ed w

ith b

asel

ine

sym

ptom

seve

rity.

Sign

ifi ca

nt im

pact

of s

tudy

on

FDA

pol

icy

for d

rug

appr

oval

.

Fact

or A

naly

sis o

f G

astr

oint

estin

al

Sym

ptom

s

NIH

W

hite

head

40-4

3 Fa

ctor

ana

lyse

s of g

astr

oint

estin

al sy

mpt

oms i

n m

ultip

le p

opul

atio

ns sh

ow th

at IB

S is

a di

stin

ct

diso

rder

but

rais

e qu

estio

ns a

bout

func

tiona

l dy

spep

sia.

Sign

ifi ca

nt im

pact

on

the

evol

utio

n of

the

Rom

e di

agno

stic

cr

iteri

a.

Valid

atio

n of

Rom

e II

I Dia

gnos

tic

Crit

eria

Rom

e Fo

unda

tion,

NIH

W

hite

head

44

Cas

e-co

ntro

l stu

dies

wer

e us

ed to

sele

ct

resp

onse

scal

es fo

r the

Rom

e II

I dia

gnos

tic

crite

ria

and

to e

valu

ate

test

–ret

est r

elia

bilit

y, se

nsiti

vity

, and

spec

ifi ci

ty.

Ala

rm S

ympt

oms i

n IB

S D

iagn

osis

Phar

mac

eutic

al,

NIH

W

hite

head

, D

ross

man

45

Obs

erva

tiona

l stu

dy sh

owin

g (1

) the

inci

denc

e of

GI c

ance

r, IB

D, a

nd m

alab

sorp

tion

in IB

S is

low

(les

s tha

n 1.

5 % ) i

n pa

tient

s with

a c

linic

al

diag

nosis

of I

BS, a

nd (2

) ala

rm sy

mpt

oms s

uch

as b

lood

in st

ools

are

of li

mite

d va

lue

in

diag

nost

ic a

sses

smen

t of F

GID

s bec

ause

they

ha

ve a

hig

h fa

lse-p

ositi

ve ra

te.

Trea

tmen

ts

CBT

Des

ipra

min

e (D

oug/

Bren

da)

NIH

D

ross

man

/Ton

er/

Whi

tehe

ad 46

In

larg

est t

reat

men

t stu

dy fo

r the

se m

odal

ities

, C

BT is

eff e

ctiv

e ov

er e

duca

tion

for t

reat

men

t of

func

tiona

l bow

el; d

esip

ram

ine

is no

t eff e

ctiv

e in

ITT

but i

s eff e

ctiv

e in

per

pro

toco

l –

drop

outs

due

to si

de e

ff ect

s.

Stud

y be

ing

cont

inue

d w

ith

Can

adia

n In

stitu

te fo

r Hea

lth

Rese

arch

(Ton

er) w

ith U

NC

as

data

man

agem

ent a

nd a

naly

sis

site.

Que

tiapi

ne

Cen

ter

Gro

ver/

Dro

ssm

an 47

C

ase

seri

es sh

owin

g au

gmen

tatio

n of

eff e

ct

with

SN

RI fo

r sev

ere

and

refr

acto

ry F

BD.

Biof

eedb

ack

for

Dys

syne

rgic

D

efec

atio

n

NIH

W

hite

head

48, 4

9 /H

eym

en 50

Se

ries

of s

tudi

es sh

owin

g th

at b

iofe

edba

ck is

eff

ect

ive

for d

yssy

nerg

ic d

efec

atio

n bu

t not

slo

w tr

ansit

con

stip

atio

n, a

nd th

at b

iofe

edba

ck

is su

peri

or to

laxa

tives

and

act

ive

plac

ebo.

Biof

eedb

ack

for

Feca

l Inc

ontin

ence

N

IH

Chi

ario

ni &

W

hite

head

51

Cas

e se

ries

show

ing

impr

ovem

ent i

n pe

rcep

tion

of re

ctal

dist

entio

n is

key

to

biof

eedb

ack-

med

iate

d im

prov

emen

t in

feca

l in

cont

inen

ce.

Ran

dom

ized

con

trol

led

tria

l sh

owin

g bi

ofee

dbac

k is

supe

rior

to

pelv

ic fl

oor e

xerc

ise

is co

mpl

eted

an

d un

der r

evie

w.

(Con

tinue

d)

Rese

arch

Dom

ain

Fund

ing

Sour

ces

Inve

stig

ator

/ Se

lect

ed P

eer R

evie

w

Publ

icat

ions

Find

ings

from

Res

earc

h Co

mm

ents

Hyp

nosis

for

Trea

tmen

t of I

BS

NIH

Pa

lsson

, Whi

tehe

ad 52

,

53

Cas

e-co

ntro

l stu

dies

dem

onst

ratin

g (1

) tha

t hy

pnos

is is

an e

ff ect

ive

trea

tmen

t for

IBS,

(2)

that

the

mec

hani

sm m

ay re

late

to c

hang

es in

hy

perv

igila

nce

for s

omat

ic se

nsat

ions

, and

(3)

self-

trea

tmen

t with

the

use

of C

Ds i

s also

eff

ect

ive.

A fo

llow

-up

stud

y sh

owin

g th

at

self-

dire

cted

gui

ded

imag

ery

is an

eff

ect

ive

trea

tmen

t for

func

tiona

l ab

dom

inal

pai

n in

chi

ldre

n is

unde

r rev

iew.

Nar

cotic

Bow

el

Cen

ter

Gru

nkem

eier

/Dal

ton/

Dro

ssm

an 54

C

ase

seri

es d

ata

char

acte

rizi

ng N

BS a

nd

show

ing

resp

onse

to d

etox

ifi ca

tion.

H

ighl

ight

ed a

s a se

min

al p

aper

for

2007

by

Am

eric

an C

olle

ge o

f Ph

ysic

ians

.

Lubi

pros

tone

Ph

arm

aceu

tical

D

ross

man

/Joh

anss

on

55, 5

6 Effi

cac

y da

ta fr

om p

hase

II a

nd II

I stu

dies

sh

owin

g be

nefi t

ove

r pla

cebo

.

REFERENCES

1 . Kanazawa M , Palsson OS , Th iwan SI , Turner MJ , van Tilburg MA , Gangarosa LM , Chitkara DK , Fukudo S , Drossman DA , Whitehead WE . Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits . Am J Gastroenterol , 2008 ; 103 ( 10 ): 2550 – 2561 .

2 . Grover M , Kanazawa M , Palsson OS , Chitkara DK , Gangarosa LM , Drossman DA , Whitehead WE . Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress . Neurogastroenterol Motil 2008 .

3 . Levy RL , Jones KR , Whitehead WE , Feld SI , Talley NJ , Corey LA . Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology . Gastroenterol 2001 ; 121 : 799 – 804 .

4 . Dorn SD , Palsson OS , Th iwan SM , Clark WC , Kanazawa M , van Tilburg MAL , Drossman DA , Scarlett Y , Levy RL , Ringel Y , Crowell MD , Olden KW , Whitehead WE . Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitiv-ity . Gut 2007 ; 56 : 1202 – 1209 .

5 . Drossman DA , Li Z , Andruzzi E , Temple R , Talley NJ , Th ompson WG , Whitehead WE , Janssens J , Funch-Jensen P , Corazziari E , Richter JE , Koch GG . U.S. Householder survey of functional gastrointestinal disorders: prevalence, sociode-mography and health impact . Dig Dis Sci 1993 ; 38 : 1569 – 1580 .

6 . Drossman DA , Morris C , Schneck S , Hu Y , Norton NJ , Norton WF , Weinland S , Dalton C , Leserman J , Bangdiwala SI . International survey of patients with IBS: Symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefi t . 2008 .

7 . Nyrop KA , Palsson OS , Levy RL , Korff MV , Feld AD , Turner MJ , Whitehead WE . Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain . Aliment Pharmacol Th er 2007 ; 26 : 237 – 248.

8 . Levy RL , Von Korff M , Whitehead WE , Stang P , Saunders K , Jhingran P , Barghout V , Feld AD . Costs of care for irritable bowel syndrome patients in a health mainte-nance organization . Am J Gastroenterol 2001 ; 96 : 3122 – 3129.

9 . Whitehead WE , Levy R.L. , Von Korff M.V , Feld AD , Palsson OS , Turner MJ , Drossman DA . Usual medical care for irritable bowel syndrome . Alimentary Pharmacology & Th erapeutics 2004 ; 20 : 1305 – 1315.

10 . Whitehead WE , for the Pelvic Floor Disorders Network . National Health and Nutrition Examination Survey (NHANES): Association of Usual Stool Consistency and Frequency with Fecal Incontinence . 108 ed . 2008 :in press.

11 . Whitehead WE , for the Pelvic Floor Disorders Network . National Health and Nutrition Examination Survey (NHANES) of fecal incontinence: Characteristics of incontinent stools . in press ed . 2008 .

12 . Whitehead WE , for the Pelvic Floor Disorders Network . National Health and Nutrition Examination Survey (NHANES) of fecal incontinence: Prevalence by sex, age, race, marital status, education, and income . in press ed. 2008 .

13 . Borello-France D , Burgio KL , Richter HE , Zyczynski H , Fitzgerald MP , Whitehead W , Fine P , Nygaard I , Handa VL , Visco AG , Weber AM , Brown MB . Fecal and urinary incontinence in primiparous women . Obstet Gynecol 2006 ; 108 : 863 – 872.

14 . Burgio KL , Borello-France D , Richter HE , Fitzgerald MP , Whitehead W , Handa VL , Nygaard I , Fine P , Zyczynski H , Visco AG , Brown MB , Weber AM . Risk fac-tors for fecal and urinary incontinence aft er childbirth: the childbirth and pelvic symptoms study . Am J Gastroenterol 2007 ; 102 : 1998 – 2004.

15 . Drossman DA , Li Z , Toner BB , Diamant NE , Creed FH , Th ompson DG , Read NW , Babbs C , Barreiro M , Bank L , Whitehead WE , Schuster MM , Guthrie EA . Functional bowel disorders: A multicenter comparison of health status, and devel-opment of illness severity index . Dig Dis Sci 1995 ; 40 : 986 – 995.

16 . Drossman DA , Leserman J , Li Z , Mitchell CM , Zagami EA , Patrick DL . Th e rating form of IBD patient concerns: A new measure of health status . Psychosom Med 1991 ; 53 : 701 – 712.

17 . Leserman J , Li Z , Drossman DA , Toomey TC , Nachman G , Glogau L . Impact of sexual and physical abuse dimensions on health status: Development of an abuse severity measure . Psychosom Med 1997 ; 59 : 152 – 160.

18 . Patrick DL , Drossman DA , Frederick IO , DiCesare J , Puder KL . Quality of life in persons with irritable bowel syndrome: Development of a new measure . Dig Dis Sci 1998 ; 43 : 400 – 411.

19 . Drossman DA , Patrick DL , Whitehead WE , Toner BB , Diamant NE , Hu YJB , Jia H , Bangdiwala SI . Further validation of the IBS-QOL: A disease specifi c quality of life questionnaire . Am J Gastoenterol 2000 ; 95 : 999 – 1007.

20 . Drossman D , Morris CB , Hu Y , Toner BB , Diamant N , Whitehead WE , Dalton CB , Leserman J , Patrick DL , Bangdiwala SI . Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment . Am J Gastroenterol 2007 ; 102 : 1442 – 1453.

21 . Leserman J , Drossman DA , Li Z , Toomey TC , Nachman G , Glogau L . Sexual and physical abuse in gastroenterology practice: How types of abuse impact health status . Psychosom Med 1996 ; 58 : 4 – 15.

22 . Drossman DA , Li Z , Leserman J , Toomey TC , Hu Y . Health status by gastrointes-tinal diagnosis and abuse history . Gastroenterol 1996 ; 110 : 999 - 1007.

23 . Ringel Y , Whitehead WE , Hu Y , Jia H , Bangdiwala SI , Drossman DA . Rectal pain thresholds are higher, not lower in IBS patients with history of sexual/physical abuse . 120 ed. 2001 : A638 .

24 . Whitehead WE , Crowell MD , Davidoff AL , Palsson OS , Schuster MM . Pain from rectal distension in women with irritable bowel syndrome: relationship to sexual abuse . Dig Dis Sci 1997 ; 42 : 796 – 804.

25 . Whitehead WE , Palsson OS , Levy RR , Feld AD , Turner M , Von KM . Comorbidity in irritable bowel syndrome . Am J Gastroenterol 2007 ; 102 : 2767 – 2776.

26 . Whitehead WE , Palsson O , Jones KR . Systematic review of the comorbidity of irritable bowel syndrome with other disorders: What are the causes and implica-tions? Gastroenterol 2002 ; 122 : 1140 – 1156.

27 . Drossman DA , Li Z , Leserman J , Keefe FJ , Hu YJ , Toomey TC . Eff ects of coping on health outcome among female patients with gastrointestinal disorders . P sychosom Med 2000 ; 62 : 309 – 317.

28 . Drossman DA , Whitehead WE , Toner BB , Diamant NE , Hu YJB , Bangdiwala SI , Jia H . What determines severity among patients with painful functional bowel disorders? Am J Gastroenterol 2000 ; 95 : 974 – 980.

29 . Drossman DA , Ringel Y , Vogt B , Leserman J , Lin W , Smith JK , Whitehead W . Alterations of brain activity associated with resolution of emotional distress and pain in a case of severe IBS . Gastroenterol 2003 ; 124 : 754 – 761.

30 . Ringel Y , Drossman DA , Leserman JL , Suyenobu BY , Wilber K , Lin W , Whitehead WE , Naliboff BD , Berman S , Mayer EA . Eff ect of abuse history on pain reports and brain responses to aversive visceral stimulation: An fMRI study . Gastroenterol 2008 ; 134 : 396 – 404.

31 . Ringel Y , Drossman DA , Turkington TG , Hawk TC , Bradshaw B , Coleman RE , Whitehead WE . Regional brain activation in response to rectal distention in patients with irritable bowel syndrome and the eff ect of a history of abuse . Dig Dis Sci 2003 ; 48 : 1774 – 1781.

32 . Dorn SD , Morris CB , Hu YJB , Toner BB , Diamant NE , Whitehead WE , Bangdiwala SI , Drossman DA . Irritable bowel subtypes defi ned by Rome II and Rome III cri-teria are similar . J Clin Gastroenterol 2008 .

33 . Drossman DA , Morris CB , Hu Y , Toner BB , Diamant N , Leserman J , Shetzline MA , Dalton C , Bangdiwala SI . A prospective assessment of bowel habit in irritable bowel syndrome in women: defi ning an alternator . Gastroenterol 2005 ; 128 : 580 – 589.

34 . Drossman DA , Morris CB , Hu YJB , Leserman JL , Dalton CB , Toner BB , Diamante NE , Bangdiwala SI . Further characterization of painful constipation (PC): Clinical features over one year and comparison with IBS . J Clin Gastroenterol 2008 .

35 . Sperber AD , Morris CB , Greemberg L , Bangdiwala SI , Goldstein D , Sheiner E , Rusabrov Y , Hu Y , Katz M , Freud T , Neville A , Drossman DA . Development of abdominal pain and IBS following gynecological surgery: A prospective, con-trolled study . Gastroenterol 2008 ; 134 : 75 – 84.

36 . Sperber AD , Morris CB , Greemberg L , Bangdiwala SI , Goldstein D , Sheiner E , Rusabrov Y , Hu Y , Katz M , Freud T , Neville A , Drossman DA . Constipation does not develop following elective hysterectomy: A prospective, controlled study . 2008 .

37 . Levy RL , Whitehead WE , Von Korff MR , Feld AD . Intergenerational transmission of gastrointestinal illness behavior . Am J Gastroenterol 2000 ; 95 : 451 – 456.

38 . Levy RL , Whitehead WE , Walker LS , Von KM , Feld AD , Garner M , Christie D . Increased somatic complaints and health-care utilization in children: eff ects of parent IBS status and parent response to gastrointestinal symptoms . Am J Gastroenterol 2004 ; 99 : 2442 – 2451.

39 . Whitehead WE , Palsson OS , Levy RL , Feld AD , VonKorff M , Turner M . Reports of “satisfactory relief ” by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately refl ect symptom improve-ment . Am J Gastroenterol 2006 ; 101 : 1057 – 1065.

40 . Whitehead WE , Crowell MD , Bosmajian L , Zonderman A , Costa PT , Jr . , Benjamin C , Robinson JC , Heller BR , Schuster MM . Existence of irritable bowel syndrome supported by factor analysis of symptoms in two community samples . Gastroenterol 1990 ; 98 : 336 – 340.

41 . Whitehead WE , Gibbs NA , Li Z , Drossman DA . Is functional dyspepsia just a subset of the irritable bowel syndrome? Baillieres Clin Gastroenterol 1998 ; 12 : 443 – 461.

42 . Whitehead WE , Bassotti G , Palsson O , Taub E , Cook EC , III , Drossman DA . Factor analysis of bowel symptoms in US and Italian populations . Dig Liver Dis 2003 ; 35 : 774 – 783.

43 . Taub E , Cuevas JL , Cook EW , III , Crowell M , Whitehead WE . Irritable bowel syn-drome defi ned by factor analysis . Gender and race comparisons. Dig Dis Sci 1995 ; 40 : 2647 – 2655.

44 . Whitehead WE . Development and validation of the Rome III diagnostic question-naire. In: Drossman DA , Corazziari E , Delvaux M , Spiller RC , Talley NJ , Th ompson WG , and Whitehead WE , eds. Rome III: Th e Functional Gastrointestinal Disorders . 3rd ed. McLean, Virginia : Degnon Associates , 2006 : 835 – 853 .

45 . Whitehead WE , Palsson OS , Feld AD , Levy RL , Von KM , Turner MJ , Drossman DA . Utility of red fl ag symptom exclusions in the diagnosis of irritable bowel syn-drome . Aliment Pharmacol Th er 2006 ; 24 : 137 – 146.

46 . Drossman DA , Toner BB , Whitehead WE , Diamant NE , Dalton CB , Duncan S , Emmott S , Proffi tt V , Akman D , Frusciante K , Le T , Meyer K , Bradshaw B , Mikula K , Morris CB , Blackman CJ , Hu Y , Jia H , Li Z , Koch GG , Bangdiwala SI . Cognitive-Behavioral Th erapy vs. education and Desipramine vs. Placebo for Moderate to Severe Functional Bowel Disorders . Gastroenterol 2003 ; 125 : 19 – 31.

47 . Grover M , Dorn SD , Weinland SR , Dalton CB , Gaynes BN , Drossman DA . Atypical antipsychotic Quetiapine in the management of severe, refractory functional gas-trointestinal disorders . 2008 .

48 . Chiarioni G , Salandini L , Whitehead WE . Biofeedback benefi ts only patients with outlet dysfunction, not patients with isolated slow transit constipation . Gastroenterol 2005 ; 129 : 86 – 97.

49 . Chiarioni G , Whitehead WE , Pezza V , Morelli A , Bassotti G . Biofeedback is supe-rior to laxatives for normal transit constipation due to pelvic fl oor dyssynergia . Gastroenterol 2006 ; 130 : 657 – 664.

50 . Heymen S , Scarlett Y , Jones K , Ringel Y , Drossman D , Whitehead WE . Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic fl oor dyssynergia-type constipation . Dis Colon Rectum 2007 ; 50 : 428 – 441.

51 . Chiarioni G , Bassotti G , Stegagnini S , Vantini I , Whitehead WE . Sensory retrain-ing is key to biofeedback therapy for formed stool fecal incontinence . Am J Gastroenterol 2002 ; 97 : 109 – 117.

52 . Palsson OS , Burnett CK , Meyer K , Whitehead WE . Hypnosis treatment for irrita-ble bowel syndrome: Eff ects on symptoms, pain threshold, and muscle tone . Gastroenterol 1997 ; 112 : A803.

53 . Palsson OS , Turner MJ , Whitehead WE . Hypnosis home treatment for irritable bowel syndrome: a pilot study . Int J Clin Exp Hypn 2006 ; 54 : 85 – 99.

54 . Grunkemeier DMS , Cassara JE , Dalton CB , Drossman DA . Th e narcotic bowel syndrome: Clinical features, pathophysiology, and management . Clin Gastroenterol Hepatol 2007 ; 5 : 1126 – 1139.

55 . Johanson J , Drossman DA , Panas R , Wahle A , Ueno R . Clinical trial: Phase 2 study of Lubiprostone for irritable bowel syndrome with constipation . Alim Pharm Th er 2008 ; 27 : 685 – 696.

56 . Drossman DA , Chey W , Panas R , Wahle A , Scott C , Ueno R . Lubiprostone signifi -cantly improves symptom relief rates in adults with irritable bowel syndrome and constipation (IBS-C): Data from two twelve-week, randomized, placebo- controlled, double blind trials . 132 ed. 2007 : 2586 – 2587 .