WO1998041153A1 - Device and method to obtain regionally representative gaseous samples from the human gastrointestinal tract used in the diagnosis of gastrointestinal disease - Google Patents

Device and method to obtain regionally representative gaseous samples from the human gastrointestinal tract used in the diagnosis of gastrointestinal disease

Info

Publication number
WO1998041153A1
WO1998041153A1 PCT/SE1998/000480 SE9800480W WO1998041153A1 WO 1998041153 A1 WO1998041153 A1 WO 1998041153A1 SE 9800480 W SE9800480 W SE 9800480W WO 1998041153 A1 WO1998041153 A1 WO 1998041153A1
Authority
WO
Grant status
Application
Patent type
Prior art keywords
tube
sampling
device
chamber
gas
Prior art date
Application number
PCT/SE1998/000480
Other languages
French (fr)
Inventor
Anders Pettersson
Lars Fändriks
Anders ÅNEMAN
Original Assignee
A+ Science Invest Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/497Physical analysis of biological material of gaseous biological material, e.g. breath
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B2010/0083Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements for taking gas samples
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0043Catheters; Hollow probes characterised by structural features

Abstract

A device for collection of gaseous NO samples from a hollow internal organ comprising a catheter tube (1) made of a gas impermeable material, and, arranged at one end of the tube (1) in communication with the tube (1), a sampling chamber (2) made of a gas permeable but liquid impermeable material. Use of the above described device for sampling of gaseous NO. A method for detection of inflammatory conditions or dysoxia in a hollow internal organ which comprises introducing a device as described above into the organ so that the sampling chamber (2) is disposed at a desired sampling site for a length of time sufficient to allow nitric oxide gas present at the sampling site to diffuse into aspirating gas contained within the sampling chamber (2), withdrawing said aspirating gas containing diffused nitric oxide gas via the catheter tube (1), and analyzing the sample for nitric oxide gas via the catheter tube (1), and analyzing the sample for nitric oxide thereby enabling detection of the said conditions.

Description

DEVICE AND METHOD TO OBTAIN REGIONALLY

REPRESENTATIVE GASEOUS SAMPLES FROM THE HUMAN

GASTROINTESTINAL TRACT USED IN THE DIAGNOSIS OF

GASTROINTESTINAL DISEASE

Field of the invention The invention relates to an endoluminal sampling catheter device and to a method for obtaining a gaseous NO sample from a hollow internal organ of a mammal.

Background of the invention The gastrointestinal epithelium represents an area of approximately 170 square meters that constitutes a protective barrier to prevent the entry of noxious sub- stances into the interior of the organism and yet must permit the selective uptake of ingested nutrients. The function of this epithelial barrier is affected in several pathophysiological conditions including cardiovascular, inflammatory and degenerative diseases. Nitric oxide (NO) as a modulator and regulator of biological processes has received increasing attention since its recognition as an endothelial derived relaxing factor (see e.g. Moncada, S., Higgs, A., The L-arginine - nitric oxide pathway, N. Eng. J. Med., 1993, 329:2002- 2012) . In particular, several additional important roles for NO in physiologic as well as pathophysiologic conditions have been discovered. With respect to the gastrointestinal epithelium, NO has been demonstrated to affect epithelial permeability, intestinal blood flow, infla ma- tory processes and secretory/absorptive capabilities (see e.g. Salzman, A. L., Nitric oxide in the gut, New Horizons, 1995, 3:38-45) .

Critical reduction of gastrointestinal blood flow and oxygenation are thought to be major contributing fac- tors to the development of multiple organ dysfunction syndrome (MODS) . MODS is the leading cause of death in

CONFIRMATION COPY modem intensive care units, largely due to our present inability to detect its early symptoms and institute prompt therapeutic measures. The intraluminal occurrence of NO may be used as a marker of gastrointestinal oxygen consumption, with decreased NO levels being characteristic of decreased oxygen utilization (see e.g. Aneman, A., Reduced NO-synthesis in the gut by endogenous NO-synthase inhibition during cardiac tamponade in pigs, Shock, 1995, suppl. vol. 3:29). In addition, by endoluminal sampling of NO, the concentration of this biologically very active compound may be directly assessed. This simple, atrau- matic technique makes other investigative approaches superfluous, including vessel catheterization (e.g. the use of heptic venous catheters to monitor splanchnic oxygen consumption) and endoluminal endoscopy, which often only provides relevant information in late stages of developing gastrointestinal ischemia.

Celiac disease (non-tropical sprue, gluten enteropa- thy) is clinically suspected by symptoms of diarrhea, weight loss, steatorrhea and malabsorption (anemia, edema and even tetany) , all of which may be features of other inflammatory bowel diseases. Hypersensitvity towards the gliadin fraction of wheat or rye gluten is considered the pathogenetic mechanism, although the exact cause of the disease is imperfectly understood. The diagnostic tools applicable to celiac disease include endoscopy and collection of biopsies for histological examination which in the typical case reveals marked atrophy of the intestinal villi and microvilli, increased depth of the intervillous cryps and a pronounced inflammatory response in the lamina propria. In addition, techniques to demonstrate malabsorption has been applied, including failure to absorb D-xylose. Biopsy procedures can potentially cause the patient considerable discomfort and are associated with risk of intestinal perforation. Moreover, the his- tologic diagnosis is only possible when severe epithelial damage is already established. Approximately 50% of adults diagnosed with celiac disease recall symptoms dating back to childhood, reflecting the difficulties in reaching an early, correct diagnosis.

Recent studies have indicated that the gastrointes- tinal epithelium contains NO synthase, the enzyme respon¬ sible for the production of NO while converting L- arginine to L-citrulline. Furthermore, several cellular elements of the ucosa may contribute to the production of NO such as monocytes, granulocytes, neurons, myocytes, enterocytes, endothelial cells and mast cells (see e.g. Salzman, A. L., Nitric oxide in the gut, New Horizons, 1995, 3:38-45). The luminal occurrence of NO may also re¬ flect acidified reduction of luminal nitrate and bacterial denitrification. Quantitative measurements of NO are made difficult by the high chemical reactivity of NO with other biological compounds, inherent with the radical properties of the NO molecule. However, NO may be detected with high specificity in a gaseous phase by chemiluminescence . There is no reliable technique described in the literature or in clinical use to quantitatively measure NO , in the human gastrointestinal tract. Previous reports on gastrointestinal NO principally rely on indirect measurements, for example citrulline from NO synthesis (see e.g. Middleton, S. J. , Shorthouse, M. , Hunter, J. 0., Increased nitric oxide synthesis in ulcerative colitis, The Lancet, 1993, 341:465-466) or met-hemoglobin from NO reacting with hemoglobin (see e.g. Wennmalm, A., Benthin, G., Petersson, A., Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygena- tion of its red cell haemoglobin, Br. J. Pharmacol., 1992, 106:507-508). A few investigations have measured NO in regurgitated air from the stomach, which may be contaminated by NO from the airways in an unknown proportion (see e.g. Lundberg, J. , Weitzberg, E., Lundberg, J. M. ,

Alving, K., Intragastric nitric oxide in humans: measurements in expelled air, Gut, 1994, 35:1543-1546). The hallmark of celiac disease is atrophy of the villous structure in the gut and a concomitant profound inflammatory reaction. As a result of these early changes, the intraluminal occurrence of NO is increased. The increase of NO cannot be discerned in regurgitated air samples due to the many confounding sources of NO in the stomach and airways .

Summary of the invention There is a need for a regional technique to sample the intraluminal atmosphere for detection of NO. Such a technique should be simple, minimally invasive, well tolerated by the patient and allow a specific and rapid analysis of NO. Moreover, in inflammatory bowel diseases such as ulcerative colitis and regional ileitis, the endoluminal levels of NO may be used to monitor the inflammatory activity in the gut, and may consequently be used for rapid and sensitive therapeutic guidance with minimal discomfort for the patient. Endoluminal NO levels may be used to detect dysoxia and to indicate whether cardiovascular supportive actions are beneficial for the situation in the gut during critical illness with reduced gastrointestinal oxygen delivery leading to an ischemic inflammatory response. The present invention provided a method and a device for obtaining regional samples of the intraluminal intestinal atmosphere for analysis of the gaseous content of NO without contamination by other endogenous sources of NO. Thus, the present invention related to a device for collection of a gaseous NO sample from a hollow internal organ of a mammal, said device comprising a catheter tube, the wall of which is made of a gas impermeable material, and, arranged at one end of the tube and in com- munication with the tube, a sampling chamber, the wall of which is made of a gas permeable but substantially liquid impermeable material. The present invention also relates to use of the above device for sampling of gaseous NO from an organ selected from the group consisting of the gut, the colon, the small intestine, and the stomach. Finally, the present invention relates to a method for detection of inflammatory conditions or conditions of dysoxia in a hollow internal organ which comprises providing a catheter having a catheter tube, the wall of said tube comprising a material which is impermeable to nitric oxide; and walled sampling chamber on the tube in communication with the interior of the tube; the wall of said walled sampling chamber comprising a material which is freely permeable to nitric oxide gas in solution but poorly permeable to liquid fluid, introducing the cathe- ter to the organ of interest so that the chamber is disposed at a desired sampling site and leaving the sampling chamber disposed at the sampling site for a length of time sufficient to allow any nitric oxide gas present at the sampling site to diffuse across the wall of the sam- pling chamber into aspirating gas contained within the sampling chamber, withdrawing at least a portion of the said aspirating gas containing any diffused nitric oxide gas via the catheter tube, analyzing the sample thus withdrawn for nitric oxide, and determining whether coeliac disease, ulcerative colitis, Crohn' s disease or dysoxia is present on the basis of nitric oxide determination.

The characterising features of the invention will be evident from the following description and the appended claims.

The method according to the invention comprises placing a flexible, gas impermeable radiopaque tube fitted with a distal gas permeable, inflatable sampling chamber in the gut of the patient. The tube is positioned via the nasal route in the proximal jejunum taking advantage of the peristalsis of the gut. In critically ill patients, a flexible guide wire inserted into a central lu- men of the catheter may be used to manipulate the catheter into the desired position. Moreover, in this latter group of patients, after withdrawal of the guide wire, the central lumen may be used for supplementing or sam- pling fluid into the proximal jejunum, thus making the catheter an ideal device for administering parenteral nutrition. The position may be verified by fluoroscopy. A defined amount of room air or specified gas mixture is used to inflate the sampling chamber. Following a speci- fied time for equilibration, the atmosphere of the sampling chamber is emptied into a gas-tight syringe for subsequent analysis of the NO content. Alternatively, the gas chamber may be emptied directly into a chemilumines- cence detector for immediate recording of the NO content. The sampling chamber represents the only part of the tube comprising gas permeable walls. Particularly silastic is preferred for construction of the sampling chamber, but also other plastic or rubber membranes known to the skilled person, can be used. The inlet and outlet lines to and from the sampling chamber are made of gas impermeable material. Particularly PEEK is preferred for construction of the channels communicating with the sampling chamber, but also other gas tight plastic or rubber materials known to the skilled person, can be used. It is im- portant that the catheter tube is impermeable to gaseous NO, to prevent the passage of NO into the sample from other parts of the body than the region where the sampling chamber is placed. This feature makes it possible to obtain a regionally representative gas sample. The invention will be further illustrated in the description of a preferred embodiment and in the examples below, which in no way are intended to limit the invention. Reference will be made to the accompanying drawings on which: Fig. 1 shows a device according to the invention;

Fig. 2 is a longitudinal sectional view of the device from figure 1; Fig. 3 is a transverse sectional view of a catheter tube comprising several channels; Fig. 4 is a diagram showing that elevated intrajejunal NO concentrations found in celiac disease are re- gional specific due to the inflammatory reaction;

Fig. 5 a-d are graphs illustrating correlations between

NO levels measured by the device according to the inventions : Fig. 6 is a graph illustrating the relation between jeju- nal NO and gastrointestinal oxygen consumption during graded hemorrhage.

Description of a preferred embodiment To simplify the device according to the invention may be described as a chamber with a "ballooned" form passed over the end of a tube.

A preferred embodiment of the device according to the invention is shown in figure 1, and also in a longitudinal sectional view in figure 2. This preferred embodiment comprises a flexible catheter tube 1 and a sampling chamber 2. The wall 3 of the catheter tube 1 of the preferred device is impermeable to gases and radiopaque; the preferred material is PEEK. The sampling chamber 2 is arranged at one end of the catheter tube 1 and in communication with the interior of the catheter tube 1. The wall 4 of the sampling chamber 2 is permeable to gas but substantially impermeable to liquids. In the preferred embodiment the sampling chamber is inflatable, and the material constituting its wall 4 is preferably silastic.

The easiest way to establish communication between the sampling chamber 2 and the interior of the catheter tube 1 is to provide at least one opening 5 in the wall 3 of the catheter tube 1 surrounded by the sampling chamber 2.

The catheter tube 1 of the device according to the invention may comprise more than one channel, this is il- lustrated in the transverse sectional view in figure 3. Preferably, a central channel 6 is arranged to accommodate a guide wire during introduction of the device into the hollow organ. This guide wire facilitates the intro- duction of the device into the patient.

This central channel 6 may be surrounded by several, e.g. 1-5, other channels. One channel 7 is in communication with the sampling chamber 2. The other channel or channels 8 are working channels constituting means in- tended to facilitate introduction of different instruments, such as optic fibers, electrodes, connecting wires, and biopsy forceps, during or after introduction of the device into the hollow organ.

Finally, the preferred embodiment also comprises a gas tight stoplock 9, such as a luer lock.

In the preferred embodiment the length of the sampling chamber 2 is 3-5 cm, and its diameter when inflated is 1 cm or less.

Examples Example 1

In this example the device according to the invention was used to obtain samples of NO from the jejunal lumen from patients suffering from celiac disease as well as from patients having suffered from celiac disease and also having been treated for the disease, and from healthy individuals constituting a control group. It was found that the jejunal luminal NO concentrations in the patients with celiac disease were more than 20 times higher than in the individuals in the control group. The mean value of the concentrations in the patients with celiac disease was 740 ppb (range 215-1690 ppb) , and the mean value for the control group was 35 ppb range (0-77 ppb). There was no overlap between the two groups. The duodenal concentrations of NO did not differ between the patients suffering from the disease and the individuals in the control group, nor did concentrations in the stomach differ significantly. The results from the measure- ments are shown in figure 4. The result clearly indicate that the elevated intrajejunal NO concentrations found in celiac disease are regionally specific due to the inflammatory reaction and not the result of NO spill-over from the stomach, and thus that the device and the method according to the invention are suitable for detection of celiac disease.

Example 2 In order to further illustrate the accurate results obtained when using the device according to the invention, four different devices according to the invention was used to obtain sample from 12 or 13 different standard aqueous solutions of NO with NO concentrations is the range of 0-490 μM. The correlations between the NO concentrations measured in the samples obtained with the devices according to the invention and the exact concentrations in the solutions are shown in figures 5 a-d.

The explanation to the fact that the concentration measured by use of the device in the standard solution with the concentration 0 μM is not 0 ppb is due to background disturbances caused by NO contained in the air.

Example 3 In this example the device according to the invention was used to determine the jejunal intraluminal concentration of NO in patients suffering from graded hemorrhage. Also the gastrointestinal oxygen consumption, V02, was determined in a conventional way known to persons skilled in the art by determining the difference between the amount of oxygen supplied in arterial blood and the amount of oxygen. The relation between jejunal NO and gastrointestinal oxygen consumption during graded hemorrhage was highly significant, which is illustrated in figure 6. This which demonstrates the sensitivity of the method according to the invention in detection of gastrointestinal dysoxia.

Claims

1. A device for collection of a gaseous NO sample from a hollow internal organ of a mammal, said device comprising a catheter tube (1), the wall (3) of which is made of a gas impermeable material, and, arranged at one end of the tube (1) and in communication with the interior of the tube (1), a sampling chamber (2), the wall (4) of which is made of a gas permeable but substantially liquid impermeable material.
2. A device according to claim 1, wherein the catheter tube (1) is flexible in order to facilitate the introduction of the device into the hollow organ.
3. A device according to claim 1 or claim 2, wherein the length of the catheter tube (1) is such that when the sampling chamber (2) is in position in the hollow organ, the other end of the tube (1) will protrude from the mouth or the rectum of the mammal.
4. A device according to any one of claims 1-3, wherein the material constituting the wall (3) of the catheter tube (1) is radiopaque.
5. A device according to any one of claims 1-4, wherein the sampling chamber (2) is inflatable.
6. A device according to any one of claims 1-5, wherein the material constituting the wall (3) of the catheter tube (1) is PEEK.
7. A device according to any one of claims 1-6, wherein means (8) are arranged in the tube (1) to facilitate the introduction of instruments such as optic fi- bers, electrodes, connecting wires, and biopsy forceps, during or after introduction of the device into the hollow organ.
8. A device according to any one of the claims 1-7, wherein a central channel (6) is arranged in the catheter tube (1), said channel (6) allowing use of a guide wire during insertion of the device into the hollow organ, or administrations of fluids into the hollow organ once the device is in position.
9. A device according to any one of the claims 1-8, wherein a gas tight stoplock (9) is arranged on the end of the catheter tube (1) not comprising the sampling chamber (2) .
10. A device according to any one of the claims 1-9, wherein means for aspiration of gas from the sampling chamber (2) through the catheter tube (1) is connected to the end of the catheter tube (1) that will protrude from the mammal when the device is placed in the hollow organ.
11. Use of a device according to any one of the claims 1-10, for sampling of gaseous NO from an organ selected from the group consisting of the gut, the colon, the small intestine, and the stomach.
12. Use according to claim 11, wherein the NO sample is used to diagnose inflammatory conditions or conditions of dysoxia.
13. Use according to claim 12, wherein the inflamma- tory condition is selected from the group consisting of coeliac disease, ulcerative colitis and Crohn' s disease.
14. Use according to claim 11, wherein the NO sample is used to monitor the inflammatory activity in the gut of a patient suffering from inflammatory bowel disease.
15. A method for detection of inflammatory conditions or conditions of dysoxia in a hollow internal organ which comprises providing a catheter having a catheter tube (1) , the wall (3) of said tube (1) comprising a material which is impermeable to nitric oxide; and walled sampling chamber (2) on the tube (1) in communication with the interior of the tube (1); the wall (4) of said walled sampling chamber (2) comprising a material which is freely permeable to nitric oxide gas in solution but poorly permeable to liquid fluid, introducing the cathe- ter to the organ of interest so that the chamber (2) is disposed at a desired sampling site and leaving the sampling chamber (2) disposed at the sampling site for a length of time sufficient to allow any nitric oxide gas present at the sampling site to diffuse across the wall (4) of the sampling chamber (2) into aspirating gas contained within the sampling chamber (2), withdrawing at least a portion of the said aspirating gas containing any diffused nitric oxide gas via the catheter tube (1), analyzing the sample thus withdrawn for nitric oxide, and determining whether coeliac disease, ulcerative colitis, Crohn' s disease or dysoxia is present on the basis of ni- trie oxide determination.
16. A method according to claim 15, wherein the inflammatory disease is selected from the group consisting of coeliac disease, ulcerative colitis and Crohn' s disease.
17. A method according to claim 15, wherein the hollow internal organ is selected from the group consisting of the gut, the colon, the small intestine, and the stomach.
18. The method of claim 15, wherein said tube (1) is made of PEEK channels.
19. The method of claim 15, wherein said tube (1) is fitted with a gas tight stoplock (9) .
20. The method of claim 15, wherein said tube (1) is fitted with accessory lines (8) to allow the introduction of instruments such as optic fibers, electrodes and connecting wires, biopsy forceps and such like.
21. The method of claim 15, wherein said tube (1) is fitted with a central channel (6) to allow the use of a guide wire to assist in placing the catheter or for ad- ministration of fluids such as parenteral nutrition solutions.
PCT/SE1998/000480 1997-03-16 1998-03-16 Device and method to obtain regionally representative gaseous samples from the human gastrointestinal tract used in the diagnosis of gastrointestinal disease WO1998041153A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
SE9701009-4 1997-03-16
SE9701009 1997-03-16

Publications (1)

Publication Number Publication Date
WO1998041153A1 true true WO1998041153A1 (en) 1998-09-24

Family

ID=20406232

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1998/000480 WO1998041153A1 (en) 1997-03-16 1998-03-16 Device and method to obtain regionally representative gaseous samples from the human gastrointestinal tract used in the diagnosis of gastrointestinal disease

Country Status (1)

Country Link
WO (1) WO1998041153A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001036969A1 (en) * 1999-11-16 2001-05-25 Aerocrine Ab Method for use in the diagnosis of food allergies and/or food intolerances
WO2002080775A1 (en) * 2001-04-04 2002-10-17 Enterix Inc. Method of collecting a gastrointestinal tract sample
US6511425B1 (en) 1997-05-30 2003-01-28 Aerocrine Ab Method for the diagnosis of food intolerance
US7306953B2 (en) 2002-07-18 2007-12-11 The University Of The West Of England, Bristol Detection of disease by analysis of emissions

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3952730A (en) * 1973-10-30 1976-04-27 National Research Development Corporation Instrument for use in the measurement of blood gases
WO1996017244A1 (en) * 1994-11-30 1996-06-06 Kjell Alving Diagnostic method for inflammatory conditions in the intestines
WO1997037587A1 (en) * 1996-04-11 1997-10-16 Kjell Alving Method and device for use in the diagnosis of inflammatory states in the urogenital tract

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3952730A (en) * 1973-10-30 1976-04-27 National Research Development Corporation Instrument for use in the measurement of blood gases
WO1996017244A1 (en) * 1994-11-30 1996-06-06 Kjell Alving Diagnostic method for inflammatory conditions in the intestines
WO1997037587A1 (en) * 1996-04-11 1997-10-16 Kjell Alving Method and device for use in the diagnosis of inflammatory states in the urogenital tract

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6511425B1 (en) 1997-05-30 2003-01-28 Aerocrine Ab Method for the diagnosis of food intolerance
WO2001036969A1 (en) * 1999-11-16 2001-05-25 Aerocrine Ab Method for use in the diagnosis of food allergies and/or food intolerances
WO2002080775A1 (en) * 2001-04-04 2002-10-17 Enterix Inc. Method of collecting a gastrointestinal tract sample
US7306953B2 (en) 2002-07-18 2007-12-11 The University Of The West Of England, Bristol Detection of disease by analysis of emissions

Similar Documents

Publication Publication Date Title
Peyrat et al. Prognostic significance of circulating p53 antibodies in patients undergoing surgery for locoregional breast cancer
Mingrone et al. Decreased uncoupling protein expression and intramyocytic triglyceride depletion in formerly obese subjects
Arvanitakis et al. Diagnosis of pancreatic disease by a synthetic peptide: A new test of exocrine pancreatic function
Hirtz The gastrointestinal absorption of drugs in man: a review of current concepts and methods of investigation.
Canani et al. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice
Kurland et al. Diagnostic tests for intestinal ischemia
US4774955A (en) Programmable dialyzer system analyzer and method of use
US4763658A (en) Dialysis system 2nd method
US4516580A (en) Continuous blood gas monitoring
Forster Exchange of gases between alveolar air and pulmonary capillary blood: pulmonary diffusing capacity
Chey et al. Prolonged effect of omeprazole on the 14 C-urea breath test
US5962335A (en) Breath test for detection of drug metabolism
US6216024B1 (en) Method and device for assessing perfusion failure in a patient
US6258046B1 (en) Method and device for assessing perfusion failure in a patient by measurement of blood flow
Rosser et al. Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis
King et al. Comparison of the 1-gram [14C] xylose, 10-gram lactulose-H2, and 80-gram glucose-H2 breath tests in patients with small intestine bacterial overgrowth
US5651769A (en) Method for retrieving pancreatic juice utilizing and endoscopically wire-guided catheter
Marik Sublingual capnography: a clinical validation study
US6264913B1 (en) Non-invasive test for assessing bacterial overgrowth of the small intestine
Benson et al. A reliable qualitative urine coproporphyrin test for lead intoxication in young children
US4830010A (en) Methods for the diagnosis of gastrointestinal disorders
D’Amico et al. An investigation on electronic nose diagnosis of lung cancer
Shandall et al. Colonic anastomotic healing and oxygen tension
US5058416A (en) Apparatus for the determination of the partial pressure of gases dissolved in a fluid
Marshall A comparison of methods of measuring the diffusing capacity of the lungs for carbon monoxide. Investigation by fractional analysis of the alveolar air

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CU CZ CZ DE DE DK DK EE EE ES FI FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase in:

Ref country code: JP

Ref document number: 1998540439

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase in:

Ref country code: CA