WO1988003389A1

WO1988003389A1 - Catheter and method for intestinal aspiration, perfusion and provocation and its use in the diagnosis of intestinal disease/allergy

Info

Publication number: WO1988003389A1
Application number: PCT/SE1987/000530
Authority: WO
Inventors: Roger Hällgren; Bo Odlind; Lars Knutsson
Original assignee: Haellgren Roger; Bo Odlind; Lars Knutsson
Priority date: 1986-11-11
Filing date: 1987-11-11
Publication date: 1988-05-19
Also published as: EP0288539A1; SE8604822L; SE8604822D0; SE455368B; AU8271387A; JPH01502484A

Abstract

A catheter for intestinal aspiration, perfusion and provocation of a segment, and a method to use this catheter for diagnostic purposes. The catheter comprises a tube (2) of flexible material with at least four lumens (3, 4, 5, 6, 7, 8) for transporting irrigation fluids, air or marker solution. Furthermore the tube is provided with holes (17, 18, 19, 20) which communicate with the lumens and the space outside the catheter. The catheter also comprises at least two inflatable balloons (9, 10), by which a segment of the small intestine can be sealed off so that a test space is formed therebetween. Furthermore the catheter comprises a stiffening wire (12) and a weight in the tip (11) of the catheter which facilitates the insertion of the catheter. The catheter is characterized in that it is formed in a way that makes it possible to insert it into the small intestine without anaesthetics and surgery. The method is characterized in that it is fast and safe and enables diagnostic use for intestinal diseases with a specificity and a sensitivity that has not previously been possible.

Description

CATHETER AND METHOD FOR INTESTINAL ASPIRATION, PERFUSION AND PROVOCATION AND ITS USE IN THE DIAGNOSIS OF INTESTINAL DISEASE /ALLERGY.

This invention relates generally to catheters and more particularly to a catheter for intestinal aspiration, perfusion and provocation of a segment of the intestine, and also to a novel method in which the catheter is used for the diagnosis of intestinal diseases/allergy, based on assays of aspirated cells, mucus and intestinal fluid with and without a provocation method. The catheter according to the invention is constructed in such a way that it combines minimal discomfort and minimal risk for the patient, with high frequency of successful insertions, quantitative yield and improved sensi¬ tivity in the diagnostic procedure.

The diagnostic methods which are available today for the investigation of suspected intestinal diseases are non¬ specific and not very sensitive. An example of a situation where improved diagnostic performance would be desirable is for the investigation of abdominal symptoms related to intolerance to foodstuffs. Also, there is a longstanding need for a method to characterize the importance of the intestine for allergic manifestations in other organs e.g. in the air ways (asthma, rhinitis) or in the skin (eczema, dermatitis herpetiformis, urticaria and other skin diseases of allergic genesis). Recently, it has been found that inflammatory processes in the small intestine could be of importance for the development and clinical outcome in some rheumatic joint diseases. The good clinical effect on joint inflammation by Salazopyrin E ^ (Pharmacia) - a drug mainly used in the treatment of chronic inflammatory bowel diseases, (Crohn's disease and ulcerative colitis), emphasizes the importance of the intestine for the development of joint diseases. Many patients with inflammatory bowel disease will be subject to surgery several times during their lifetime. The routine methods available today for assessing inflammatory changes in the small intestine are unsatisfactory. Thus, there is a great need for improved diagnostic procedures to decide when surgical treatment is necessary. Celiac disease (hyper- sensitivity to gluten) is a relatively common disease in the intestine. It is, however, not uncommon that the final diagnosis is delayed.

The immune system of the intestine is quantitatively the largest immunological component in the human body and there is an increasing interest to characterize its role in different diseases. Thus, there is a growing need for methods enabling direct studies of the local immune system in the small bowel.

Taking all the above information into consideration it is desirable and important to develop improved diagnostic methods for, but not limited to:

1/ Characterizing the importance of the small intestine for the genesis and development of different diseases in and outside the intestine, which in itself can entail novel diagnostic and therapeutic methods.

2/ Characterizing the pathophysiological course of known intolerance against foodstuffs in order to develop improved diagnostic methods and/or therapy.

3/ Characterizing the inflammatory process in the small intestine in cases of suspected intolerance against foodstuffs. It is desirable to be able to directly provocate the intestine with a foodstuff /allergen with the aim of improving the diagnostic procedure in these conditions, and also to make this procedure less time-consuming and cheaper.

4/ Evaluation of pathophysiology, and thereby prognosis and therapy in case of established inflammatory bowel disease, such as Crohn's disease, ulcerative colitis or graft versus host reaction.

5/ Assessing the type and intensity of inflammatory/ immunological reactions in cases of suspected involvement of the small intestine in e.g. rheumatic diseases. This approach can be used to explain mechanisms of action of existing therapy or in the development of new modes of treatment.

6/ Examination of unclear spasmodic conditions of the small bowel (irritable bowel syndrome).

Diagnostic methods available at present for investigations of the above mentioned diseases comprise X-ray examinations (with or without the use of contrast medium), biopsy of the small intestine with histopathological evaluation, chemical analysis- of faeces (excrement), faecal cultures and microscopic assay of faeces. In cases of suspected food allergy the patient undergoes so called exclusion diet, which often means spending weeks in hospital. The patient is initially on a basic diet and different foodstuff components are supplemented in a stepwise fashion until a clinical reaction occurs.

These known techniques give diagnostic, certain prognostic and pathophysiological information in cases of obvious disease in the small intestine, but are of very little or no value for illuminating more subtle processes in the small intestine which can be anticipated in e.g. rheumatic disease or food allergy. Exclusion diet for the demonstration of food allergy, is a time-consuming and expensive method with poor accuracy.

Perfusion and aspiration studies of the intestine including assays of the intestinal fluid contents of ions have been described previously. Technical difficulties include those due to contamination from intestinal fluid from adjacent areas of the intestine. A practically useful technique for controlled perfusion of a s egment of the small intestine , creating a 'closed' space in the intestine has not previous ly been described. The present invention provides a method for the refined immunological and other assays which are essential for the objects 1-6 above.

In the patent literature there are several catheters described for examining and treating diseases in several different organs. However, no catheter has yet been developed which can be inserted in the small intestine without surgery and with which a precis e segment of the small intestine can be "shut off" for investigational purpose. Several patents relate to diseases in the oesophagus (US-2 854 982, US-A 4 180 076) . The construction of these catheters is such that they cannot be inserted into the small intestine and therefore they cannot be used for the investigation of a speci ic segment of the small intestine. - ^*

US-4 368 739 relates to a catheter intended for the smal l intestine, but this catheter is inserted in connection with surgery, when the patient is under anaesthes ia and the abdominal wall is opened. Moreover, the inflated balloons are only Intended for moving the catheter in the intestine by ways of manipulation. Thus , it cannot be used to establish a 'physiological' segment.

Derwent's abstract No. E0417C/18 , SU-683 756 , relates to a catheter with two inflatable balloons which probably can be used in the small intestine. No example of its intended use is given. It seems doubtful that this catheter can be inserted successfully since it lacks 1) a guiding wire and 2) a weight in the end of the catheter. We have found these two features to be essential for a functioning catheter. Moreover, this catheter has a distance of 20-30 cm between the inflatable balloons. This would tend to delay the insertion into the intestine and also impede drainage from the segment due to the fact that some of the holes in the segment will be 'plugged' by the intestinal wall. Also with this design contamination of the perfusion fluid cannot be excluded, since this design only has one lumen (2) for in- and outflow of perfusion fluid, which in turn will give assay results which are not reproducible. Separate lumens for in- and outflow is another basic feature of the catheter according to our invention and a condition for accurate provocation studies.

In an article from Gastroenterology 1986:91:370-8 (Isenberg et al) the use of a catheter to isolate a 4 cm segment of the duodenum to study the bicarbonate secretion is described. This catheter is far too thick for insertion into the small intestine and, thus, assays in the small intestine cannot be performed with this catheter.

Therefore, one object of the present invention is to provide a catheter for advanced diagnostic purposes which can be successfully inserted into the small intestine (jejunum/ileum) of unanaesthetized patients with a minimum of risk or discomfort. Another object of the present invention is to provide a method for diagnosing and characterizing diseases particularly in the small intestine. This method also provides the opportunity to study the response of the intestine to different types of provocations, performed locally in a chosen segment of the intestine. The method can be used as an out-patient procedure. Analyses of one or more of the components of the intestinal content such as cells, mucus and fluid will probably generate novel and important information about the physiology and pathophysiology of the intestine. A catheter according to the invention satisfies the following crucial requirements: a) the patient is submitted to a minimum of discomfort, b) the catheter is designed according to anatomical principles in order to minimize the risk for the pat ient . Thu s , there i s no ri sk of p enetration o f the intestinal wall. Also, the test s egment can be shut off securely between the two balloons, preventing exposure outside the test segment. Moreover, the insertion procedure with the catheter is rapid, to minimize radiation exposure from X-ray, c) there are separate lumens for in- and outflow of perfusion fluid, so that contamination is avoided and a continuous perfusion generating quantitative information is guaranteed. Due to the construction of the catheter, the patient is exposed to a minimal risk during - allergen provocation because the method invo lves 1 ) low concentrations of allergen, 2 ) local exposure of only a few percent of the whole small intestine and 3 ) only for a short time (the provocation fluid can be evacuated at any time) .

The idea behind the present invention is thus to offer a c athete r sy s tem and a method fo r d iagnos is o f d i s ease processes in the small intestine.

The catheter system requires :

1/ That a specific intestinal segment can be reached easily by a catheter, the construction of which is based on anatomic principles .

2/ That this intestinal segment can be isolated from the rest of the intestine between two inflatable balloons. The number of different lumens must be such that it is pos s ible to continuous ly guarantee, with the aid of several marker substances, that there is no contamination worth mentioning from the intestinal portions outside the segment.

3 / That there are completely separate lumens for in- and outflow of perfusion fluid, enabling provocations with allergen to be performed without contamination. A perfusion system of the above type, which is practical and clinically useful, and which, as far as can be foreseen, fulfils the safety requirements for the patient during the investigation, is obtained with a catheter and a method according to the characterizing part of claim 1 and claim 8, respectively.

In the following a preferred embodiment of the invention is described in details in connection with the accompanying drawings, in which

Fig. 1 is a schematic view of the catheter according to the present invention,

Fig. 2 is a cross-sectional view of the catheter,

Fig. 3 shows the position of the catheter when it has been brought into position in the small intestine, and also a small catheter for draining the stomach, and

Fig. 4 is a schematic view of the proximal end of the catheter.

The embodiment in Fig. 1 shows a catheter (1) mainly comprising a tube (2) of PVC, alternatively polyurethane or a similar material, having a length of 175-550 cm. A typical catheter for jejunum is 175-180 cm in length and has a diameter of 4-7 mm. A typical jejunal catheter for adults has a diameter between 4,5 and 5,5 mm.

The cross-section of the tube is seen in Fig. 2. It has two larger central lumens (3 and 4) extending in parallel and occupying a major part of the volume of the tube. In the perifery of the catheter there are four smaller lumens (5, 6, 7 and 8). A tube of this kind can be produced by injection moulding in a manner known per se. On the tube there are at least two inflatable balloons (9 and 10) preferably of silicon, latex or polyurethane. These balloons are spaced from each other with an internal distance of approx. 10 cm. This distance has been found to give an optimal intestinal surface for the perfusion. A longer distance between the balloons has been found to impede drainage from the segment because some of the holes in the segment therebetween will be 'plugged' by the intestinal wall. The pressure in the balloons should be well under the normal diastolic blood pressure (70-80 mm Hg) to avoid pressure damages on the intestinal wall. With a balloon pressure as low as used in the present invention, the catheter can be in its position for several days without risking any damage on the intestinal wall of the patient. Filled with approx. 40 ml air the balloons will obtain a diameter of 3-4 cm. The distal balloon (9) is placed at a distance not less than 10 cm from the tip of the catheter, because otherwise the tip will not be sufficiently flexible, and this in turn will make the insertion _.of the catheter more difficult.

In one of the central lumens (4) a stiffening metal wire (12) is located. The wire is preferrably coated with a plastics material, e.g. Teflon*. This wire is used during the insertion (see Fig. 3) to give the catheter increased rigidity. This enables easier insertion of the catheter through the stomach and past the pylorus (13). After passing the pylorus the wire is pulled back a little bit making the tip (11) of the catheter easily flexible again so that it can follow the contour of the intestine. When the catheter has passed the duodenum and the remainder of the fixed portion of the intestine, the wire can be completely pulled out; the catheter "migrates by itself" due to the contractions of the intestine.

In the tip (11) of the catheter there are 15-20 cylindrical weights (14) of e.g. tungsten with a diameter of 3 mm and a length of 5 mm. 15 mm from the tip of the catheter there is a plastic plug (16) separating the three most distally positioned tungsten weights. This gives the tip (11) of the catheter partly higher rigidity, partly it is possible to localize the tip of the catheter by X-ray when it is placed in the human body.

When the catheter is in its intended position and the balloons have been inflated, a physiological perfusion fluid is added to the closed space (segment) between the balloons through one of the larger central lumens (3). The fluid enters the segment through a centrally located hole (17) and is drained through the other central lumen (4) through several holes (18) placed over the whole length of the segment. The use of different lumens for in- and outflow of the perfusion fluid guarantees that there is no contamination in the lumens. One of the central lumens (3) is closed with a plastic plug (15) distally of the hole (17), to avoid a 'sump effect' in the tip. The other central lumen (4) extends all the way to the weight (14), enabling the wire (12) to be inserted as far distally as possible. The lumens (6 and 7) are intended for air supply for the purpose of inflating the balloons (9^' and 10). The lumens (5 and 8) are used for marker solutions, different for different groups of patients. The solutions can be directed out of the catheter through the holes (19 and 20) on each side of the segment. This is extremely important to guarantee that no leakage worth mentioning occurs past the balloons. Alternatively, lumens (5 and 8) and holes (19 and 20) can be used for drainage.

The jejunal catheter according to the invention can be formed with several lumens and balloons. Thereby several separate segments of the intestine can be provided simultaneously for very sofisticated studies of processes in the intestine.

Fig. 4 shows that the proximal connections for the lumens are provided with self-sealing connections (22) for instance of Luer-type and with pressure balloons (23) for the lumens leading to the inflatable bal loons . Also , it is pos sible to provide the air lumens with a pressure guard system for registration of the pressure in the balloons.

Across the whole length of the catheter there is an X-ray marker (21 ) for X-ray identi fication of the catheter when inserted. The test segment itself is provided with specific X- ray markers (24) .

In the following the method according to the invention will be illustrated by way of an example.

Example

The investigation can be performed on out patients. No other preparation except overnight fasting is required of the patient.

To perform an investigation using a jejunal catheter according to the invention, the catheter is inserted through the patients mouth, which can be done with the patient unanaesthetized (in some cases light spraying of the pharynx with a local anaesthetic will be necessary or at least make the insertion more comfortable). Thanks to the small diameter of the catheter it is very easy to insert (swallow) the catheter through the oesephagus and down into the stomach; this is preferably done by the patient himself/herself. The wire positioned in the catheter gives the catheter such a rigidity, and the tungsten plates give the tip such a weight, that it is very easy to insert the catheter through the stomach and past the pylorus into the intestine. Without wire and weight, this is a difficult task and in certain cases it will be almost impossible. When the catheter has passed the pylorus the wire is pulled back a bit so that the tip regains its flexibility. Thanks to the construction of the catheter tip it is now possible to advance the catheter to a desirable position in the upper part of the jejunum.

When the catheter has been brought into the desired position in the small intestine this is controlled by X-ray. Thereafter the upper balloon is inflated and the downstream portion of the intestine is perfused a while to irrigate intestinal content e.g. food, bile or pancreatic enzymes out of the intended portion for the segment. This balloon will also block the entry of bile and pancreatic enzymes into the perfusion segment. Thereafter the lower balloon is inflated so that a delimited and biologically closed space is obtained. As used here, biologically closed of course does not mean that the space is hermetically sealed, this only involves a geometric delimitation of a segment of the intestine under physiological conditions. This also means that body fluids outside the segment are transported away in a natural way or drained through external draining e.g. through some of the lumens comprised in the catheter- according to the present invention. By using marker solutions, it can be continuously verified that the system is 'sealed'. The catheter is suitably anchored outside the body so that it does not continue to move down in the intestine due to the intestinal contractions, or it is possible to let the catheter migrate down itself and thereby investigate sequential segments of the intestine. A separate, very thin catheter is preferably inserted in the stomach to thereby discharge the secretion of the stomach. The system is now ready to be used for the desired investigation. This can be done in several different ways depending on the kind of investigations that is being performed. Initially one always irrigate the segment through the lumens 3 and 4 with isotonic solutions so that undesired intestinal content is discharged from the system. The segmental perfusion according to the invention offers a method for extremely sensitive and specific biological assays of the intestinal content. Also, it enables that e.g. drugs which can be dangerous when the whole surface of the intestine is exposed can be added locally in the intestine. This also enables that the perfusion fluid can be provided with components or substances which protect cells, mucus or biological subs tances from being destroyed or inactivated. This will increase the yield of the analytes and the accuracy of the analys is . This physiologically clos ed segment also enables a system which is simpler and safer for the patient and which will ^'improve diagnostic possibilities as exemplified by the following diagnostic procedures:

Allergic conditions

The component suspected to cause the allergic reaction is introduced in different concentrations (provocation) into the closed and perfused segment of the small intestine. When the component has been in contact with the small intestine for a predetermined time the segment is irrigated through lumens 3 and 4. The irrigation fluid is thereafter analysed with respect to its contents of substances , which in case of allergic-inflammatory response from the cells of the small intestine exist in increased concentrations in the irrigation fluid. The procedure involves : a/ time limited exposure of allergen, b/ local exposure of al lergen to a very small part of the intestine, c/ increased sensitivity in the assay systems of the perfusion liquid, and d/ lower concentrations of allergen. Thus, a positive response of such a provocation is local and asymptomatic contrary to the pres ently avai lab le method which entai ls general exposure of the intestine and is intended to provoke symptoms.

The method according to the pres ent invention provides reproducible results at very low allergen concentrations . A 1000- 10000 fold dilution of the normally exi sting dose of allergen In e. g. foodstuff gives a reliable response of the sma ll intestine. An example of a substance which we have analysed after provocation with an allergen is histamine. An increase in histamine concentration in the irrigation fluid is an apparent feature in cases of provocation with subs tances against which the patient is allergic. Hyaluronan is another interesting analyte. Specific antibodies may be investigated.

Inflammatory diseases of the small intestine

In this diagnostic approach it is intended to investigate the i rr i gat i on f l u id f rom th e pe r f u s ed i nt e s t i na l s egm e nt regarding inf lammatory and other cel l s , lymphocytes and products released from such cells . It is also possible e.g. to characteriz e the surface antigens of the enterocyte s . Our studies show that patients with different inflammatory bowel diseas es have a changed cel l pattern and changed release of cell products. These alterations have significant diagnostic, prognostic and therapeutical implications.

To verify that quantitative information is obtained a constant flow .of marker substances must occur through the lumens 5 and 8. The marker solutions can contain either colouring agents or radioactive markers. In case of radioactive markers they could be attached to large sugar molecules, which makes it impossible for the human body to absorbe them.

Thus, the aforementioned objects have been obtained with the present invention. Thanks to the construction of the catheter according to the present invention it can be inserted with a minimum of discomfort for the patient. The insertion of the catheter is performed through the mouth and can be done by the patient himself/herself. Moreover, the catheter is constructed in such a way that the risks connected with catheters according to prior art are essentially avoided. The catheter according to the present invention is stable and soft, so that the intestinal wall of the patient will not be damaged, but not so soft that it bends. Thanks to the unique channel system of the catheter it can be guaranteed that perfusion fluid does not leak outside the specific delimited intestinal segment or that the perfusion fluid is contaminated with intestinal contents from outside the perfused segment. Furthermore, the X-ray dosis the patient is exposed to during investigation using the catheter is very low due to the fact that the catheter according to the present invention has such a length and construction that it can be inserted very fast into a desired position in the small intestine.

The jejunal catheter according to the invention provides an opportunity for clinical research and routine diagnosis concerning diseases related to the small intestine. This opportunity to accurately diagnose and treat intestinal diseases has not previously existed.

Another useful application of the catheter is in the study of gastro-intestinal physiology and pharmacology. In the case of physiology one can get quantitative information e.g. regarding flow rates and composition of bile and pancreatic.fluid. In the case of pharmacology one can obtain quantitative information (e.g. regarding dose-response relationship) about effects on the intestine.

It is also possible to perform sofisticated pharmacokinetic studies with the catheter e.g. regarding bile excretion of drugs or extent and physico-chemical characteristics of intestinal drug absorption.

Yet another potential application for the new catheter is its use in local therapy. An isolated segment of the Intestine is then treated with a substance without risking that other parts of the intestine will be affected.

The characteristics and features of the appended claims are incorporated in the scope of this invention described in the specification.

Claims

1. Catheter for intestinal aspiration, perfusion and provocation, comprising a tube (2) of flexible material, provided with several lumens (3, 4, 5, 6, 7, 8) and holes (17,

18, 19, 20) extending through the wall of the tube into thereto belonging lumen, at least two inflatable balloons (9,

10) for sealing of a closed test segment therebetween, a releasable wire (12) and a weight in the tip (11) of the catheter, c h a r a c t e r i z e d in that the catheter is formed for insertion without surgery in such a way that the catheter is at least 160 cm long and has a diameter of 4-7 mm, in that the catheter comprises at least four lumens (3, 4, 5,

6, 7, 8) for transport of for example irrigation fluids, air or marker solution, in that the holes (17, 18, 19, 20) are situated at the balloons (^'9, 10), at, proximally and distally of the test segment. and each communicate with a respective lumen, in that the distal balloon (9) is placed at least 10 cm from the tip (11) of the catheter and approx. 10 cm from the proximal balloon (10), in that the wire (12) is releasably placed in one of the central lumens (4) to facilitate the insertion of the catheter in the intestine, and in that the tip (11) of the catheter is provided with several plates of heavy material, e.g. tungsten, to increase its weight and further facilitate the insertion of the catheter.

2. Catheter according to claim 1, c h a r a c t e r i z e d in that irrigation fluid, which if desirable contains provocative agents, is added to the test segment in a lumen (3) through a thereto belonging hole (17) and drained in another lumen (4) through a thereto belonging hole (18).

3. Catheter according to claim 1 or 2, c h a r a c t e ¬ r i z e in that holes (19, 20), which communicate with lumens (5) and (8) respectively, are arranged in the catheter on suitable spots for providing of specific marker solutions by which leakage can be indicated by assaying the liquids in the system.

4. Catheter according to claims 1-3, c h a r a c t e r i ¬ z e d in that the pressure of the balloons (9, 10) should be well under 75-80 mm Hg.

5. Catheter according to claims 1-4, c h a r a c t e r i ¬ z e d In that the tube (2) is mould injected from e.g. PVC- plastic, and in that the balloons (9, 10) are made of silicon, latex or polyurethane.

6. Catheter according to claims 1-5, c h a r a c t e r i ¬ z e d in-that the catheter (1) is provided with an X-ray marker (21) across its total length and with specific X-ray markers (24) at the test segment, and in that the tip (11) of the catheter is provided with 15-20 plates of tungsten, which after the three most distally situated plates are interrupted by a plastic plug (16) for facilitating the localization of the tip (11) of the catheter.

7. Catheter according to claims 1-6, c h a r a c t e r i ¬ z e d in that the lumen (3) comprised in the tube (2) is closed with a plastic plu'g (15) distally of the hole (17) to avoid sump effect in the lumen (3) which leads material into the intestine.

8. Method for diagnosing intestinal diseases or other diseases related to changes in the pathophysiology of the intestine, and/or for studying the small intestine, by closing a specific test segment using a catheter comprising a tube (2) with lumens (3, 4, 5, 6, 7, 8) and holes (17, 18, 19, 20), at- least two inflatable balloons (9, 10) for sealing off a closed test segment therebetween, a wire (12) and a weight in the tip (11) of the catheter, c h a r a c t e r i z e d in a) that a catheter according to claims 1-7 is rapidly inserted and with great accuracy to a specific segment of the small intestine through the mouth, whereby the wire (12) in the lumen (4) is used to make the catheter more rigid until the catheter has passed the duodenum and reached the movable portion of the intestine after which it is pulled out and the catheter migrates itself, b) that the position of the specific intestinal segment can be correctly established by specific X-ray markers (24) which are situated on each side of the test segment, c) that the balloons (9, 10) are inflated when the test segment is in correct position, d) that neutral or provocative irrigation fluids are inserted in the space, e) that the irrigation fluids are collected after a predetermined time in the segment of the small intestine, to give a quantitative yield without contamination from materials outside the segment, e.g. food, bile, pancreatic fluid and proteolytic enzymes, f) that the irrigation fluids are assayed regarding chemical and/or biological contents (cells or cell products), and in g) that results from such assays are used to characterize type and intensity of the local inflammatory response and therefore are of value for the diagnosis of e.g. food allergy or inflammatory bowel disease.

9. Method according to claim 8, c h a r a c t e r i z e d in that the neutral irrigation fluids are isotonic.

10. Method according to claim 8, c h a r a c t e r i z e d in that the provocative irrigation fluids contain allergens.

11. Method according to claim 8, c h a r a c t e r i z e d in that the provocative irrigation fluids comprise specific agents for, e.g., studying enzymatic disturbances.

12. Method according to anyone of the claims 8-11, c h a r a c t e r i z e d in that markers, for example radioactive substances or colouring agents, are continuously added through the lumens (5, 8) to the holes (19, 20), which are situated on each side of the test segment, so that a possibly existing leakage can be found and compensated for at assay calculation.

13. Method according to anyone of the claims 8-12, c h a r a c t e r i z e d in that different types of markers are continuously added through the lumens (5, 8) to the holes (19, 20) before the neutral or provocative irrigation fluids are inserted in the system, and in that the liquid in the test segment is drained for assay after a certain time, whereby the assay results then specifically indicate which one of the balloons (9, 10) possibly is leaking and this can be dealt with by inflating this particular balloon.

14. Method according to claim 8, c h a r a c t e r i z e d in that the perfusion liquid is analysed regarding for instance flow rates, composition of bile and pancreatic fluid to give quantitative information in the study of gastro¬ intestinal physiology.

15. Method according to claim 8, c h -a r a c t e r i z e d in that the perfusion liquid is analysed regarding effects on the intestine, for Instance dose-response-relationship and bile excretion of drugs or extent and physio-chemical characteristics of intestinal drug absorption to give quantitative information about the gastro-intestinal pharmacology.