Postgrad MedJ 1997; 73: 1-7 © The Fellowship of Postgraduate Medicine, 1997
`
`Classic diseases revisited
`
`The irritable bowel syndrome
`
`Carol Y Francis, PJ Whorwell
`
`Summary
`is a
`Irritable bowel syndrome
`common disorder varying
`in
`severity from trivial to incapaci(cid:173)
`tating. The pathophysiology and
`epidemiology are gradually being
`unravelled and it is now becoming
`apparent just how poor the quality
`oflife.ofsome of these patients can
`be. It is no longer acceptable
`practice to diagnose the condition
`and discharge the patient on a
`high fibre diet, particularly as the
`latter can often make the situation
`worse. Although hard to treat,
`worthwhile responses can be
`achieved by careful targeting of
`therapy to the many different
`facets of the disorder.
`
`Keywords:
`
`irritable bowel syndrome
`
`IBS:mostcommon
`symptoms
`
`• abdominal pain or discomfort (any
`site)
`• abnormal bowel habit
`• abdominal distension
`• feelings of incomplete evacuation
`• mucus per rectum
`
`Box 1
`
`IBS: prevalence
`
`• 15% - 20% of Western population
`• female:male ratio 2.5: 1
`• up to 50% attending gastrointestinal
`clinic
`• also common in third world
`
`Box2
`
`Department of Medicine,
`University Hospital of South
`Manchester,
`Nell Lane, West Didsbury,
`Manchester M20 2LR, UK
`CY Francis
`PJ Whorwell
`
`Accepted 7 February 1996
`
`is a functional disorder of the gut,
`Irritable bowel syndrome (IBS)
`characterised by abdominal pain, abdominal distension and some abnorm(cid:173)
`ality of bowel habit (box 1). It is extremely common (box 2), affects females
`more than males and recent reports suggest that it is just as common in the
`third world as in developed countries. 1 JBS remains a challenging condition
`to treat as there are no diagnostic tests and, until recently, little has been
`known about the underlying pathophysiology. However, important develop(cid:173)
`ments are taking place which hopefully will lead to better management of the
`condition. One recent milestone has been the introduction of guidelines
`allowing a more confident diagnosis of IBS to be made and this has been
`useful both
`in
`the clinical and
`research setting. Furthermore,
`the
`pathophysiology of the disorder is now becoming more clearly understood,
`suggesting that it may reflect a combination of disordered motor function
`and visceral sensation.
`The concept that JBS is a purely psychosomatic condition is now not tenable,
`although psychological factors have an important role to play in disease
`exacerbation and perpetuation. It is probably best to consider the disorder as
`multifactorial in origin, with psychopathology being just one of many
`contributing factors.
`
`Signs and symptoms
`
`ABDOMINAL PAIN
`Apart from a small subgroup of patients presenting with painless diarrhoea,
`JBS patients commonly complain of pain of varying severity. It is usually
`intermittent or colicky and is occasionally so severe that some women may
`even equate its intensity to that of labour pains. It is now appreciated that pain
`can arise from both the large and small bowel and indeed may be felt at just
`about any site within the abdomen. 2 Continuous abdominal pain is sometimes
`observed and is more common in patients exhibiting psychopathology. This
`particular form of JBS is extremely hard to treat and often has a poor
`prognosis.
`
`ABDOMINAL DISTENSION
`Abdominal distension is an intriguing symptom that is poorly understood and
`which on occasions can be extremely prominent. Patients may find it a very
`intrusive feature of their disorder whilst members of the medical profession are
`inclined to dismiss it as being trivial. It is usually at its mildest in the morning,
`worsening as the day progresses such that some patients have to loosen clothing or
`even change to a larger size. It has been suggested that this complaint may be an
`artefact but studies utilising computed tomography have confirmed that distension
`is a real and measurable feature. 3 It also appears to be unrelated to intraluminal
`gas4' 5 and as yet no convincing explanation has been advocated, although an
`abnormality of tone coupled with enhanced visceral sensitivity is possible.
`
`DISTURBED DEFECATION
`This varies from diarrhoea in which patients complain of frequent loose
`motions often worse on first rising in the morning to constipation which can
`either mean straining frequently to pass small pellet-like stools or only passing
`stools infrequently (fewer than three stools per week). It is not uncommon for
`patients who frequently open their bowels only to pass hard pellets to be
`erroneously classified as having diarrhoea. This is because only the numerical
`frequency of bowel action has been taken into account rather than a detailed
`enquiry about stool consistency being made. This is a very important practical
`point as it may result in constipated patients being given inappropriate
`treatment with antidiarrhoeals.
`Many patients will alternate between episodes of diarrhoea and constipation.
`Often there is associated mucus which may be quite excessive but IBS does not
`cause rectal bleeding and this should be investigated appropriately. Other
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`2
`
`Francis, Whorwell
`
`ms: noncolonic symptoms
`
`• nausea
`• early satiety
`• dysphagia
`• lethargy
`• back pain
`• thigh pain
`• urinary frequency
`• urinary urgency
`• dyspareunia
`• fibromyalgia
`
`Box3
`
`The Rome criteria
`
`Continuous or recurrent symptoms for
`at least three months of:
`• abdominal pain, relieved with
`defecation, or associated with a
`change in frequency or consistency
`of stool
`and/or
`• disturbed defecation at least 25% of
`the time, ie, two or more of:
`-altered stool frequency
`-altered stool form
`-altered stool passage (straining or
`urgency, feeling of incomplete
`evacuation),
`-passage of mucus
`usually with
`• bloating or feeling of abdominal
`distension
`
`Box4
`
`common symptoms are urgency of defecation and a feeling of incomplete
`evacuation of the rectum. Incontinence is occasionally encountered and is a
`particularly devastating symptom.
`
`NONCOLONICSYMPTOMS
`Patients with IBS often suffer a whole variety of noncolonic symptoms6 (box 3)
`such as backache and lethargy which are important for a number of reasons.
`Firstly, they can lead to the patient being referred to the wrong specialty with a
`series of inappropriate and unrewarding investigations. Secondly, they may lead
`to the patient worrying about the possibility of coexistent disease. Thirdly,
`patients do not readily complain of these features for fear of being labelled as a
`polysymptomatic complainer and lastly, because 50% of patients with IBS
`actually rank a noncolonic feature of their disorder as being more intrusive than
`the classical symptoms of abdominal pain, distension and abnormal bowel
`habit. 7 Furthermore, it has recently been shown that noncolonic symptoms may
`even have diagnostic potential8 in that they can help to substantiate the
`diagnosis in patients with atypical symptoms such as those presenting with
`abdominal pain and a normal bowel habit. The more noncolonic symptoms that
`are present, the more likely is the diagnosis to be IBS. 8
`The problem of inappropriate referral resulting from noncolonic symptoma(cid:173)
`tology should not be underestimated. It has been shown that over 50% of
`women attending gynaecology clinics with abdominal pain are suffering from
`symptoms consistent with IBS9•10 and a similar figure has recently been
`reported in the urological setting. 11 Furthermore, dyspareunia is surprising}!
`common in women with IBS and can have a profound impact on their lives. 1
`
`PHYSICAL SIGNS
`Although there are no pathognomonic physical signs of IBS, there are some
`features that are commonly observed which may aid diagnosis. Physical
`examination is also essential to help exclude organic disease.
`Patients usually look well. Abdominal tenderness is common, varies from
`mild to severe and may occur at any site although it is most often observed in
`the left iliac fossa. Abdominal distension may be observed, particularly if the
`patient is seen near the end of the day. A palpable mass is sometimes felt in the
`right iliac fossa but characteristically on continued palpation becomes less well
`defined. Fielding13 also described a right iliac fossa squelch sign in a third of
`patients. Scars from previous abdominal surgery are frequently seen,
`particularly those of cholecystectomy, appendicectomy and various gynaecolo(cid:173)
`gical interventions. Finally, during sigmoidoscopic examination, patients'
`symptoms may be reproduced and spasm of the colon can be observed.
`
`Making a cffnical diagnosis
`
`A number of clinicians have addressed the question of how to make a positive
`clinical diagnosis of IBS given the constraints of a lack of diagnostic tests. 14•15
`These have been validated over the years and in 1989 by international
`consensus, diagnostic criteria (known as the Rome criteria, box 4 16) were
`compiled and are now widely used both in the clinical and research setting.
`These criteria could represent a major step forward as long as they are updated
`in the light of ongoing experience.
`
`Investigations
`
`General practitioners should be encouraged to try and diagnose IBS confidently
`and positively with minimal investigation. This should be relatively easy in
`milder forms of the disorder but problems start to arise when patients fail to
`respond to the usual measures of education, reassurance and standard
`medication. It is at this stage, particularly if there is concern about the security
`of the diagnosis, that hospital referral has to be contemplated. Even in the
`hospital setting, investigation can often initially be limited to a full blood count,
`erythrocyte sedimentation rate and sigmoidoscopy. Additional tests such as
`biochemistry, stool culture, lactose tolerance test, thyroid function tests or
`jejunal biopsy may have to be contemplated. Occasionally, estimation of the
`daily stool weight is helpful, as values over 200 g tend to suggest a diagnosis
`other than IBS. In patients over the age of 45 or younger patients with a family
`history of cancer of the colon, breast, ovary or uterus, a colonoscopy or barium
`enema should be undertaken.
`It is important to recognise that, because it is so common, IBS can coexist
`with other disorders. It has been shown, for example, that in a group of patients
`with ulcerative colitis in remission there is a high prevalence of IBS
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`Irritable bowel syndrome
`
`?hoc\
`
`i~'
`
`d i e t a r y -+ .+ - infection
`factors
`
`I
`
`\
`
`antibiotics
`surgery
`Figure 1 Aetiology/physiology of IBS
`
`3
`
`symptoms. 17 Similarly, in a patient with an established diagnosis of IBS, it is
`important to be alert to the fact that other disorders may supervene and the
`doctor should be sensitive to changes in symptom patterns or the appearance of
`new features.
`
`Aetiology/pathophysiology
`
`The cause of IBS is not known, however, the condition is highly likely to be
`multifactorial in origin (figure 1). There is undoubtedly a tendency for the
`condition to run in families, suggesting a genetic predisposition but to date no
`gene abnormality has been demonstrated. In the asymptomatic individual with
`an underlying potential for developing IBS, it is thought that some event is
`necessary to trigger the onset of symptoms. A number of exacerbating or
`triggering factors are now well recognised and include abdominal surgery,
`antibiotic usage, gastrointestinal infections, inappropriate diet, stress and sleep
`deprivation. 18' 19 It seems reasonable to assume that there may be many other
`precipitating factors as yet to be defined.
`Traditionally, IBS has been regarded as a purely motor disorder but more
`recently, abnormalities of visceral sensitivity are assuming an equally important
`role. The notion that IBS is a purely psychological condition is probably no
`longer acceptable but undoubtedly, psychopathology plays an integral role in
`modifying the motor and visceral responses of the gut.
`
`INTESTINAL MOTOR FUNCTION
`A whole variety of motor abnormalities of both the small and large bowel have
`been described in patients with IBS. Unfortunately, many of these do not
`correlate well with clinical findings and symptoms. Perhaps one of the most
`consistent features is an exaggerated response to stimuli such as intravenous
`cholecystokinin,20 balloon distension,21 and meals. 22 High-amplitude contrac(cid:173)
`tions have been noted in some IBS patients during episodes of crampy
`abdominal pain. 22 Since the heightened pressure appears before the pain it
`seems likely that spasm produces pain rather than vice versa. Hypermotility of
`the small bowel has also been found in association with pain. 2
`The fact that not all patients seem to display a motility disorder yet still
`respond to antispasmodics suggests that perception of motor events may be
`abnormal rather than the event itself and this forms part of the concept of
`visceral hypersensitivity.
`
`VISCERAL HYPERSENSITIVITY
`Ritchie 13 was the first to show that patients with IBS report pain at lower
`distension volumes and/or pressures than asymptomatic controls when the
`rectum is distended. Over the years, interest has grown in the concept of an
`abnormality of visceral sensation and sensitivity in different areas of the gut has
`been explored. We have recently shown that the whole length of the gut is
`abnormally sensitive to balloon distension in a group of patients with IBS. This
`'hypersensitivity' could explain symptoms such as rectal fullness, urgency,
`incomplete evacuation, bloating and tenderness of the sigmoid colon to
`palpation or internal distension. In addition, patients with IBS have also been
`shown to exhibit urological abnormalities23 and this, taken in conjunction with
`the recently reported high incidence of fibromyalgia 24 suggests a more diffuse
`abnormality of nociception.
`Hypersensitivity at the mucosal level might mean that patients sense luminal
`events or motor events abnormally. The mechanisms underlying the develop(cid:173)
`ment of this hypersensitivity remains to be established, but diarrhoea can
`sensitise the rectum25 and there is some evidence to suggest that psychological
`factors have a similar effect. 26
`
`PSYCHOPATHOLOGY
`Stress undoubtedly affects the gastrointestinal system in health, as any student
`prior to an exam is well aware. Nevertheless, the role of stress and psychological
`factors in IBS is probably overrated as only a quarter of those with symptoms of
`IBS present to a doctor, 27 and studies have shown that whilst there is a high
`prevalence of psychopathology among hospital IBS patients, those who do not
`consult have a normal psychological profile compared to the general
`population. 28 This suggests that it may be something to do with the
`psychopathology rather than the symptoms of IBS that make patients seek
`help for their gut symptoms. This might include coping capacities or illness
`behaviour although no clear cut relationship has so far been found with
`personality profile, psychiatric illness or set of stress factors. However as most
`studies have only been done in specialist centres on difficult cases, the
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`4
`
`Francis, Whorwell
`
`relationship between JBS and psychological factors will probably only be
`including
`understood when more data are available on communities
`noncomplaining subjects.
`
`Who should be refened for specialist care?
`
`The usual reasons for hospital referral are failure to respond to treatment or
`uncertainty over the diagnosis (figure 2) but other factors are worthy of
`consideration. Some patients certainly appear to become entrenched in their
`disease and in order to try and prevent such a vicious circle being established,
`early referral might be worth contemplating. However, in order to achieve this
`goal the consultant concerned should have a special interest in the disorder, or
`the strategy may be counterproductive. A further advantage of referral to
`specialised units is that motility and visceral sensitivity testing can be
`undertaken and it is our experience that patients find this extremely beneficial
`as, for the first time, they are actually having tests yielding relevant data and, on
`occasions, positive results.
`
`Treatment
`
`PATIENT EDUCATION
`Like many other medical conditions, fear of the implications of a set of
`symptoms understandably creates much worry and anxiety. Once the diagnosis
`has been reliably established and the necessary investigations completed,
`probably the most important therapeutic measure is a careful explanation of
`what IBS is, with emphasis on the benign nature of the condition. It is especially
`important that the legitimacy of the condition is emphasised and that the patient
`is not told "there is nothing wrong with you". The noncolonic features of the
`disorder also need to be addressed, as they are often a source of great concern to
`the patient and some, particularly the lethargy, not immediately amenable to
`therapy. A number of individuals cope better with their symptoms with no
`further medical intervention once they have been given a sympathetic
`explanation. Patients need to understand that the disorder is not curable in
`the true sense of that word and has a tendency to fluctuate over time. However
`this does not mean that considerable help cannot be offered and once realistic
`expectations are established, coping capacities usually improve.
`
`DIET/FIBRE
`For many years, dietary fibre has been advocated as the primary line of
`treatment for IBS. This dogma has recently been challenged with evidence that
`
`l at
`/~
`t
`l
`
`patient education
`and dietary
`modification
`
`antispasmodics
`antidiarrhoeals
`laxatives
`
`no response
`
`GP
`symptoms of IBS
`
`history of cancer
`positive diagnosis
`
`Yes
`
`No--------l
`
`Hospital
`
`Evaluation
`
`positive diagnosis
`
`Yes
`
`No
`
`+
`/~
`!
`!
`further 7r·"
`
`reassurance +-- IBS other disease
`I
`t
`antispasmodics
`combination therapy
`I
`t . .
`low do,r,cyche,
`
`appropriate
`treatment
`
`transcutaneous
`nerve stimulation
`
`exclusion
`diet
`
`hypnotherapy,
`psychotherapy
`
`Figure 2
`
`IBS flow chart
`
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`Irritable bowel syndrome
`
`5
`
`fibre, particularly that derived from wheat can actually make patients worse. 29
`Indeed no fewer than 55% of IBS patients claim that bran makes them worse,
`with only 10% deriving benefit. Thus patients should be left to use bran more
`according to their needs.
`A number of patients report that certain foods appear to exacerbate their
`symptoms. The problem with this observation is that the process of eating
`itself can bring on symptoms as well as the content of what is eaten, and this
`is well demonstrated by the fact that sham feeding or even thinking of food
`can actually promote gut motility. 30 Thus, distinguishing between true food
`intolerance and some form of heightened neurohumoral response to eating
`can prove extremely difficult. However, occasionally some people appear to
`be genuinely intolerant of certain foods and if this can be identified, can
`prove useful. Reports of the efficacy of exclusion diets vary considerably31
`but when they are undertaken it is probably best to enlist the help of an
`interested dietitian.
`
`CURRENT DRUG THERAPY
`It is probably fair to say that there is no single drug of outstanding efficacy for
`the treatment of IBS and currently the best initial approach is a process of trial
`and error utilising combinations of antispasmodics, bulking agents or
`antidiarrhoeals/laxatives where appropriate.
`
`Antispasmodics
`As the abdominal pain of IBS was originally thought to be due to excessive
`colonic contractions, antispasmodics have become widely used in the treatment
`of this condition. Despite more recent evidence questioning the role of spasm,
`they are undoubtedly helpful in some patients, particularly when the pain is
`colicky and intermittent and it may be that even reducing the strength of a
`normal but abnormally sensed contraction is worthwhile. There are two main
`groups of antispasmodics - smooth muscle relaxants such as alverine and
`mebeverine, and anticholinergics such as dicyclomine. Patients may respond in
`whole or part to different preparations and it is worth trying a number over a
`period of time. It is also important to remember that 'as necessary' dosing with
`these drugs is sometimes preferable to continuous medication, particularly
`when patients have intermittent symptoms.
`Antispasmodics are also worth trying for abdominal distension but this is
`often difficult to treat and if there is no response, peppermint oil or even a
`reduction of dietary fibre is worth a try.
`
`Antidiarrhoeal agents/laxatives
`Antidiarrhoeal agents such as loperamide and diphenoxylate are useful for
`patients whose main complaint is of frequent loose stools. The dose required
`varies considerably and it is often best to leave the patient to work out the
`optimum regime bearing in mind that PRN use is perfectly reasonable. Patients
`often feel quite guilty about using excessive amounts of antidiarrhoeals, so
`should be reassured that they are a very safe group of drugs which can be used
`on a long term basis without fear of serious consequences. They may also be
`very useful in patients suffering from urgency and incontinence.
`Constipation may respond to simple stool bulking agents such as ispaghula
`but if these fail, lactulose is worth trying, although the latter can be nauseating
`and sometimes exacerbate abdominal distension. In more refractory cases, it
`may be necessary to resort to stronger laxatives such as sodium picosulphate.
`Occasionally, patients get a good response from over the counter laxatives such
`as senna and bisacodyl and as long as these are safe, they should not be
`prohibited. As with antidiarrhoeals, individual titration of the dose may be
`required and the patient reassured that the long-term detrimental effect of
`laxatives has probably been overrated.
`
`Antidepressants
`It has been suggested that the tricyclic antidepressants may have a beneficial
`effect in IBS which is mediated via a mechanism other than their antidepressant
`activity. 32 This is based on the fact that patients often respond to much lower
`doses than those required for depression and sometimes, in contrast to their
`antidepressant action, response is almost immediate. Their anticholinergic
`activity might also contribute to their beneficial effect. They are not
`recommended as first line therapy and are best reserved for the more refractory
`patient. Sometimes, their antidiarrhoeal properties can be used to advantage
`but in the constipated variety of IBS, some help with bowel habit may be
`needed. The efficacy of the newer types of antidepressants, such as the selective
`serotonin re-uptake inhibitors, has yet to be evaluated.
`
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`6
`
`Francis, Whorwell
`
`FUTURE DRUG THERAPY
`Current therapy for IBS is far from satisfactory3 3 and as yet, there are no agents
`available which modify visceral sensitivity. This therapeutic hiatus coupled with
`a better understanding of the pathophysiology of IBS has led to the
`pharmaceutical industry taking a greater interest in developing more effective
`medication.
`
`Gut-specific anticholinergi,cs
`The use of anticholinergics is often limited by their atropine-like side-effects.
`This problem could be minimised if more gut-specific antimuscarinics were
`available. This might also have the advantage that higher doses of these drugs
`could be used.
`
`5-Hydroxytryptamine (serotonin) receptor antagonists
`Serotonin appears to be intricately involved in the mediation of visceral
`sensitivity which is now known to be abnormal throughout the entire length of
`the gut in patients with IBS. 34 Preliminary data suggests that agents modifying
`various serotonin receptor subtypes might have therapeutic potential and a
`number are in development.
`
`Cholecystokinin antagonists
`Some patients are particularly intolerant of fatty foods and this is thought to be
`mediated through the release of cholecystokinin, a gut hormone which is known
`to increase intestinal motility. 35 Administration of exorenous cholecystokinin
`has been shown to reproduce the symptoms of IBS 3 and indeed has been
`suggested as a diagnostic test for the condition. These observations have led to
`the development of antagonists of cholecystokinin (eg, loxiglumide) which are
`now undergoing clinical trials.
`
`Kappa receptor agonists
`There are a number of subtypes of the opioid receptor including mu, gamma
`and kappa. Their anatomical distribution varies considerably with kappa
`receptors concentrated in the gut. It has been argued that agonists of kappa
`receptors might promote gut specific analgesia and preliminary data on
`fedotozine (a kappa agonist) has shown some beneficial effects. This approach
`to 'gut analgesia' is appealing as it may relieve symptoms without necessarily
`having to modify the underlying pathophysiology which could be different in
`different cases.
`
`NON-DRUG THERAPY
`
`Transcutaneous nerve stimulation
`This treatment, based on electrical stimulation, is widely used for the treatment
`of pain and has been tried in patients with IBS with approximately 51 % of
`patients showing some response. 37 It is worth trying where pain is a prominent
`feature but it should be pointed out that the other symptoms of IBS do not
`usually respond.
`
`Hypnosis/psychotherapy
`Despite all the measures described above, 25% of patients will remain refractory
`to treatment or even deteriorate. Both hypnotherapy38 and psychotherapy39
`have been shown in clinical trials to be very useful in such patients. However,
`these treatments are very specialised, time consuming and unfortunately only
`currently provided in relatively few centres, although it is to be hoped that their
`availability may increase with the passage of time.
`
`Prognosis
`
`It is probably best to warn the patient that IBS is a long-term problem, with a
`tendency to exacerbations and remissions. It is surprising how much can be
`achieved by a process of patient education, coupled with therapeutic
`experimentation, advice on avoiding precipitating factors and measures to
`improve coping capacity. Specific negative
`terms such as
`'incurable',
`'untreatable' and 'nothing can be done for you' must on no account be used.
`
`Conclusion
`
`It is only just beginning to be realised how great the social impact of IBS can be,
`both in terms of quality of life of the individual and the economy of the
`community as a whole. 40' 41 For these reasons and the fact that the condition
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`Irritable bowel syndrome
`
`7
`
`can be so miserable for the sufferer, IBS and the related functional bowel
`disorders deserve to be placed much higher on the list of priorities for the
`research and development of new therapies.
`
`Olubutide IO, Olawuyi F, Fasanmade AA. A
`study of irritable bowel syndrome diagnosed by
`Manning criteria in an African population. Dig
`Dis Sci 1995; 40: 983- 5.
`2 Horowitz L, Farrar yr. lntraluminal small
`intestinal pressure in normal patients and in
`patients with functional gastrointestinal disor(cid:173)
`ders. Gasm>enrerology 1962; 42: 455 -64.
`3 Maxton DG, Martin DF, Whorwell PJ, Godfrey
`M. Abdominal distension in female patients
`with IBS: an investigation of possible mechan(cid:173)
`isms. Gut 1991; 32: 662-4.
`4 Lasser RB, Bond JH, Levin MD. The role of
`intestinal gas in functional abdominal pain. N
`Eng/JMed 1975; 293: 524-6.
`5 Maxton DG, Whorwell PJ. Abdominal disten(cid:173)
`sion in irritable bowel syndrome: the patient's
`perception. Eur J Gastroenrero/ Hepawl 1992; 4:
`241-3.
`6 Whorwell PJ, McCallm M, Creed FH, Roberts
`CT. Noncolonic features of irritable bowel
`syndrome. Gut 1986; 27: 37-40.
`7 Maxton DG, Morris JA, Whorwell PJ. Ranking
`of symptoms by patients with irritable bowel
`syndrome. BMJ 1989; 299: 1138.
`8 Maxton DG, Morris J, Whorwell PJ. More
`accurate diagnosis of irritable bowel syndrome
`by the use of non colonic symptomatology. Gut
`1991; 32: 784-6.
`9 Prior A, Wilson K, Whorwell PJ, Farragher EB.
`Irritable bowel syndrome in the gynaecological
`clinic: a survey of 798 new referrals. Dig Dis Sci
`1989; 34: 1820 -4.
`10 Prior A, Whorwell PJ. Gynaecological consulta(cid:173)
`tions in patients with irritable bowel syndrome.
`Gut I 989; 30: 996- 8.
`11 Francis CY, Duffy JN, Whorwell PJ, Morris J.
`High prevalence of irritable bowel syndrome in
`patients attending urological outpatient depart(cid:173)
`ments. Gasm>enrerology 1996; 110: A666 (Dig
`Dis Sci I 996; in press).
`12 Guthrie E, Creed FH, Whorwell PJ. Severe
`sexual dysfunction in women with irritable
`bowel syndrome: a comparison with inflamma(cid:173)
`tory bowel disease and duodenal ulceration.
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