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Intestinal permeability: An overview

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      Abstract

      The noninvasive assessment of intestinal permeability in humans has a 20-year history. Because the tests are increasingly used in clinical practice and research and because there is much controversy, we reviewed the literature and outlined the potential and possible shortcomings of these procedures. Data was obtained from personal files and from a systemic search through MEDLINE and EMBASE. The principle of the differential urinary excretion of orally administered test markers is explained with reference to the desired physicochemical properties of the markers and how the principle can be exploited to allow assessment of various other gastrointestinal functions. The use of intestinal permeability tests for diagnostic screen for small bowel disease and assessment of responses to treatment, the pathogenesis of disease, normal intestinal physiology, and the effect of drugs and toxins on the intestine is described and reviewed. The controversy surrounding the anatomic location of the permeation pathways that the markers use is highlighted. Noninvasive tests of intestinal permeability have fulfilled early promises of usefulness in clinical practice and research. There is now a need for integrated research into the basic mechanisms of regulatory control of the intestinal barrier function.

      Abbreviations:

      AIDS (acquired immunodeficiency syndrome), PVP (polyvinylpyrrolidione), 99mTc-DTPA (99mTc-diethylene-triaminopentaacetate)
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      References

        • Menzies IS
        Absorption of intact oligosaccharide in health and disease.
        Biochem Soc Trans. 1974; 2: 1040-1046
        • Menzies IS
        Transmucosal passage of inert molecules in health and disease.
        in: Skadhauge E Heintze K Intestinal absorption and secretion. 8th ed. Falk Symposium 36. MTP, Lancaster1984: 527-543
        • Cooper BT
        The small intestinal permeability barrier.
        in: Losowski MH Heatley RV Gut defences in clinical practice. Churchill Livingstone, Edinburgh1986: 117-132
        • Bjarnason I
        • Peters TJ
        • Levi AJ
        Intestinal permeability: Clinical correlates.
        Dig Dis Sci. 1986; 4: 83-92
        • Sanderson IR
        • Walker WA
        Uptake and transport of macromolecules by the intestine: possible role in clinical disorders (an update).
        Gastroenterology. 1993; 104: 622-639
        • Fordtran JS
        • Rector FC
        • Locklear TW
        • Ewton MF
        Water and solute movement in the small intestine of patients with sprue.
        J Clin Invest. 1967; 46: 287-298
        • Menzies IS
        • Pounder R
        • Heyer S
        • Laker MF
        • Bull J
        • Wheeler PG
        • Creamer B
        Abnormal intestinal permeability to sugars in villus atrophy.
        Lancet. 1979; 2: 1107-1109
        • Cobden I
        • Hamilton I
        • Rothwell J
        • Axon ATR
        Cellobiose/mannitol test: physiological properties of probe molecules and influence of extraneous factors.
        Clin Chim Acta. 1985; 148: 53-62
        • Maxton DG
        • Bjarnason I
        • Reynolds AP
        • Catt SD
        • Peters TJ
        • Menzies IS
        Lactulose, 51CrEDTA, l-rhamnose and polyethylene glycol 400 as probe markers for “in vivo” assessment of human intestinal permeability.
        Clin Sci. 1986; 71: 71-80
        • Bjarnason I
        • Maxton D
        • Reynolds AP
        • Catt S
        • Peters TJ
        • Menzies IS
        A comparison of 4 markers of intestinal permeability in control subjects and patients with coeliac disease.
        Scand J Gastroenterol. 1994; 26: 630-639
        • Jenkins AP
        • Nukajam WS
        • Menzies IS
        • Creamer B
        Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid.
        in: A test to distinguish colonic from small-intestinal permeability change. 8th ed. Scand J Gastroenterol. 27. 1992: 769-773
        • Maxton DG
        • Catt SD
        • Menzies IS
        Combined assessment of intestinal disaccharidases in congenital asucrasia by differential urinary disaccharide excretion.
        J Clin Pathol. 1990; 43: 406-409
        • Maxton DG
        • Catt SD
        • Menzies IS
        Intestinal disaccharidases assessed in congenital asucrasia by differential urinary disaccharide excretion.
        Dig Dis Sci. 1989; 34: 129-131
      1. Bjarnason I, Smethurst P, Batt R, Catt S, Maxton D, Menzies IS. Differential urine excretion of disaccharides for the noninvasive assessment of intestinal disaccharidase activities: effects of α-glucosidase inhibitors and primary hypolactasia, and the correlation between in vivo and in vitro measurements of sucrase, lactase and isomaltase activity in patients with coeliac disease (submitted).

        • Noone C
        • Menzies IS
        • Banatvala JE
        • Scopes JW
        Intestinal permeability and lactulose hydrolysis in human rotaviral gastroenteritis assessed simultaneously by non-invasive differential sugar permeation.
        Eur J Clin Invest. 1986; 16: 217-225
        • Sutherland LR
        • Verhoef M
        • Wallace JL
        • Rosendaahl GV
        • Crutcher R
        • Meddings JB
        A simple, non-invasive marker of gastric damage: sucrose permeability.
        Lancet. 1994; 343: 998-1000
        • Chadwick VS
        • Phillips SF
        • Hofman AF
        Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.
        Gastroenterology. 1977; 73: 241-246
        • Chadwick VS
        • Phillips SF
        • Hofman AF
        Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to study of normal and abnormal permeability states in man and animals.
        Gastroenterology. 1977; 73: 247-251
        • Aldwinckle TJ
        • Ahkong QF
        • Bangham AD
        • Fisher D
        • Lucy JA
        Effects of poly (ethylene glycol) on liposomes and erythrocyte permeability changes and membrane fusion.
        Biochem Biophys Acta. 1982; 189: 548-560
        • Wilson CG
        • Thomas NW
        Interaction of tissues with polyethylene glycol vehicles.
        Pharm Int. 1984; 13: 94-97
        • Irving CS
        • Lifschitz CH
        • Marks LM
        • Nichols BC
        • Klein PD
        Polyethylene glycol polymers of low molecular weight as probes of intestinal permeability. I. Innovations in analyses and quantitation.
        J Lab Clin Med. 1986; 107: 290-298
        • Magnusson KE
        • Sundqvist T
        Modelling of intestinal permeability in man to polyethylene glycols (PEG 400 and PEG 1000).
        Acta Physiol Scand. 1985; 125: 289-296
        • Dahlqvist A
        Specificity of human intestinal disaccharidases and implications for hereditary disaccharide intolerance.
        J Clin Invest. 1962; 41: 463-470
        • Menzies IS
        Quantitative estimation of sugars in blood and urine by paper chromatography using direct densitometry.
        J Chromatogr. 1983; 81: 109-127
        • Kynaston JA
        • Fleming SC
        • Laker MF
        • Pearson ADJ
        Simultaneous quantification of mannitol, 3-O-methyl glucose, and lactulose in urine by HPLC with pulsed electrochemical detection, for use of intestinal permeability.
        Clin Chem. 1993; 39: 453-456
        • Fleming SC
        • Kapemba MS
        • Laker MF
        • Levin GE
        • Griffin GE
        Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability.
        Clin Chem. 1990; 36: 797-799
        • Kapembwa MS
        • Fleming SC
        • Sewankambo N
        • Serwadda D
        • Lucas S
        • Moody A
        • Griffin GE
        Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects.
        Clin Sci. 1991; 81: 327-334
        • Laker MF
        • Bull HJ
        • Menzies IS
        Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man.
        Eur J Clin Invest. 1982; 12: 485-491
        • Bjamason I
        • Peters TJ
        • Veall N
        A persistent defect of intestinal permeability in coeliac disease as demonstrated by a 51Cr-labelled EDTA absorption test.
        Lancet. 1983; 1: 323-325
        • Bjarnason I
        • Levi S
        • Smethurst P
        • Menzies IS
        • Levi AJ
        Vindaloo and you.
        BMJ. 1988; 297: 1629-1631
        • Bjamason I
        • Smethurst P
        • Fenn GC
        • Lee CF
        • Menzies IS
        • Levi AJ
        Misoprostol reduces indomethacin induced changes in human small intestinal permeability.
        Dig Dis Sci. 1989; 34: 407-411
        • Bjamason I
        • Smethurst P
        • Clarke P
        • Menzies IS
        • Levi AJ
        • Peters TJ
        Effect of prostaglandins on indomethacin induced increased intestinal permeability in man.
        Scand J Gastroenterol. 1989; 29: 97-103
        • Ravin HA
        • Seligman AM
        • Fine J
        Polyvinylpyrrolidone as a plasma expander: studies on its excretion, distribution and metabolism.
        N Engl J Med. 1952; 247: 921-929
        • Utter O
        Om sakaros-toleransch och avsandringen. I. Hos barn.
        Finska Laksakksk Handl. 1927; 69: 613-619
        • Wheeler PG
        • Menzies IS
        • Creamer B
        Effect of hyperosmolar stimuli and coeliac disease on the permeability of the human gastrointestinal tract.
        Clin Sci Mol Med. 1978; 54: 495-501
        • Laker MF
        • Menzies IS
        Increase in human intestinal permeability following ingestion of hypertonic solutions.
        J Physiol (Lond). 1977; 273: 881-894
        • Dobson A
        • Sellers AF
        • Gatewood VH
        Dependence of CrEDTA absorption from the rumen of luminal osmotic pressure.
        Am J Physiol. 1976; 231: 1595-1600
        • Kameda H
        • Abei T
        • Nasrallah S
        • Iber FL
        Functional and histological injury to intestinal mucosa produced by hypertonicity.
        Am J Physiol. 1968; 214: 1090-1095
        • Erlij D
        • Martinez-Palomo AM
        Opening of tight junctions in frog skin by hypertonic solutions.
        J Membr Biol. 1972; 9: 229-240
        • Martinez-Palomio A
        Structure of tight junctions in epithelia with different permeability.
        in: 8th ed. Proc Natl Acad Sci USA. 72. 1975: 4487-4491
        • Madara JL
        Increases in guinea pig small intestinal transepithelial resistance induced by osmotic loads are accompanied by rapid alterations in absorptive-cell tight junctional structure.
        J Cell Biol. 1983; 97: 125-136
        • Cobden I
        • Rothwell J
        • Axon ATR
        Intestinal permeability and screening tests for coeliac disease.
        Gut. 1980; 21: 512-518
        • Kessler M
        • Acuto O
        • Storelli C
        • Murer H
        • Muller M
        • Semanza G
        A modified procedure for the rapid preparation of efficiently transporting vesicles from small intestinal brush border membranes.
        Biochem Biophys Acta. 1978; 506: 136-154
        • Hamilton I
        Small intestinal permeability.
        in: 8th ed. Recent advances in gastroenterology. Volume 6. Churchill Livingstone, Edinburgh1986: 73-91
        • Laker MF
        The effect of hypertonic solutions on intestinal permeability.
        in: 8th ed. Doctoral Thesis. University of London, 1978
        • Ukabam SO
        • Cooper BT
        Small intestinal permeability to mannitol, lactulose, and polyethylene glycol 400 in coeliac disease.
        Dig Dis Sci. 1984; 29: 809-816
        • Blatzinger JG
        • Rommel K
        • Ecknauer R
        Elimination of low molecular weight polyethylene glycol 400 in the urine following oral load, as a measure of intestinal permeability.
        J Clin Chem Clin Biochem. 1981; 19: 265-266
        • Ma TY
        • Hollander D
        • Krugliak P
        • Katz K
        PEG 400, a hydrophilic molecular probe for measuring intestinal permeability.
        Gastroenterology. 1990; 98: 39-46
        • Hollander D
        • Koyama S
        • Dadufalsa V
        • Tran DQ
        • Krugliak P
        • Ma TY
        • King KY
        Polyethylene glycol 900 permeability of rat intestinal and colonic segments in vivo and brush border membrane vesicles in vitro.
        J Lab Clin Med. 1989; 113: 505-515
        • Krugilak P
        • Hollander D
        • Ma TY
        • Tran D
        • Dadufalza VD
        • Katz KD
        • Le K
        Mechanism of polyethylene glycol 400 permeability of perfused rat intestine.
        Gastroenterology. 1989; 97: 1164-1170
        • Hollander D
        Crohn's disease—a permeability disorder of the tight junctions?.
        Gut. 1988; 26: 1621-1624
        • Iqbal TH
        • Lewis KO
        • Cooper BT
        Diffusion of polyethylene glycol-400 across lipid barriers in vitro.
        Clin Sci. 1993; 85: 111-115
        • Hollander D
        • Rickets D
        • Boyd CAR
        Importance of ‘probe’ molecular geometry in determining intestinal permeability.
        Can J Gastroenterol. 1988; 2: 35A-38A
        • Ma TY
        • Hollander D
        • Bhalla D
        • Nguyen H
        • Krugliak P
        IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability.
        J Lab Clin Med. 1992; 120: 329-341
        • Madara JL
        • Trier JS
        Structural abnormalities of jejunal epithelial cell membranes in coeliac sprue.
        Laborat Invest. 1980; 43: 254-261
        • Hollander D
        The intestinal permeability barrier.
        in: A hypothesis as to its regulation and involvement in Crohn's disease. 8th ed. Scand J Gastroenterol. 27. 1992: 721-726
        • Martinez-Palomo A
        • Meza I
        • Beaty G
        • Cereijido M
        Experimental modulation of occluding junctions in a cultured transporting system.
        J Cell Biol. 1980; 87: 736-745
        • Madara JL
        • Stafford J
        • Berenberg D
        • Carlson S
        Functional coupling of tight junctions and microfilaments in T84 monolayers.
        Am J Physiol. 1988; 254: G416-G423
        • Marcial MA
        • Carlson SL
        • Madara JL
        Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationship.
        J Membr Biol. 1984; 80: 59-70
        • Gumbiner B
        Structure, biochemistry, and assembly of epithelial tight junctions.
        Am J Physiol. 1987; 253: C749-C758
        • Cobden I
        • Dickinson RJ
        • Rothwell J
        • Axon ATR
        Intestinal permeability assessed by excretion ratios of two molecules: Results in coeliac disease.
        BMJ. 1978; 2: 1060
        • Juby LD
        • Rothwell J
        • Axon ATR
        Lactulose/mannitol test.
        in: An ideal screening test for coeliac disease. 8th ed. Gastroenterology. 96. 1989: 79-85
        • Hamilton I
        • Cobden I
        • Axon ATR
        Intestinal permeability in coeliac disease: the response to gluten withdrawal and single dose gluten challenge.
        Gut. 1982; 23: 202-210
        • Stenhammer L
        • Stromberg S
        Intestinal permeability to lactulose/l-rhamnose in children with coeliac disease and other gastrointestinal disorders.
        J Pediatr Gastroenterol Nutr. 1988; 7: 304-306
        • Gawkrodger DJ
        • McDonald C
        • O'Mahony S
        • Ferguson A
        Small intestinal function and dietary status in dermatitis herpetiformis.
        Gut. 1991; 32: 377-382
        • Bjarnason I
        • Marsh MN
        • Price A
        • Levi AJ
        • Peters TJ
        Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis.
        Gut. 1986; 26: 1214-1219
        • Sanderson IR
        • Boulton P
        • Menzies IS
        • Walker-Smith JA
        Improvement of abnormal lactulose/rhamnose permeability in active Crohn's disease of the small bowel by an elemental diet.
        Gut. 1987; 28: 1073-1076
        • Teahon K
        • Smethurst P
        • Levi AJ
        • Bjarnason I
        The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease.
        Gastroenterology. 1991; 101: 84-89
        • Teahon K
        • Smethurst P
        • Macpherson AJ
        • Levi AJ
        • Menzies IS
        • Bjarnason I
        Intestinal permeability in Crohn's disease and its relation to disease activity and relapse following treatment with elemental diet.
        Eur J Gastroenterol Hepatol. 1993; 5: 79-84
        • Wyatt J
        • Vogelsang H
        • Hubl W
        • Waldhoer T
        • Lochs H
        Intestinal permeability and the predictor of relapse in Crohn's disease.
        Lancet. 1993; 341: 1437-1439
        • Bjarnason I
        • Macpherson AJ
        • Somasundaram S
        • Teahon K
        Non-steroidal anti-inflammatory drugs and inflammatory bowel disease.
        Can J Gastroenterol. 1993; 7: 160-169
        • Bjarnason I
        • Macpherson AJS
        • Somasundaram S
        • Teahon K
        Non-steroidal anti-inflammatory drugs and Crohn's disease.
        in: Scholmeric J Kruis W Goebbell H Hohenberger W Gross V Inflammatory bowel diseases: pathophysiology as basis of treatment. 8th ed. Falk Symposium No 67. Kluwer Academic, Lancaster1993: 208-222
        • Forget P
        • Sodoyez-Goffaux F
        • Zapitelli A
        Permeability of the small intestine to 51CrEDTA in children with acute gastroenteritis or eczema.
        J Pediatr Gastroenterol Nutr. 1985; 4: 393-396
        • Ford RPK
        • Menzies IS
        • Phillips AD
        • Walker-Smith JA
        • Turner MW
        Intestinal sugar permeability: relationship to diarrhoeal disease and small bowel morphology.
        J Pediatr Gastroenterol Nutr. 1985; 4: 568-574
        • Ukabam SO
        • Homeda MA
        • Cooper BJ
        Small intestinal permeability in Sudanese subjects: evidence of tropical enteropathy.
        Trans R Soc Trop Med Hyg. 1986; 40: 204-207
        • Behrens RH
        • Lunn PG
        • Northrop CA
        • Hanlon PW
        • Neale G
        Factors affecting the integrity of the intestinal mucosa of Gambian children.
        Am J Clin Nutr. 1987; 45: 1433-1441
        • Davin JC
        • Forget P
        • Mahieu PR
        Increased intestinal permeability to (51Cr)EDTA is correlated with IgA immune complex-plasma levels in children with IgA-associated nephropathies.
        Acta Pediatr Scand. 1988; 77: 118-124
        • Ramage JK
        • Stanisz A
        • Scicchitano R
        • Hunt RH
        • Perdue MH
        Effects of immunologic reactions on rat intestinal epithelium.
        in: Correlation of increased intestinal permeability to chromium 51 labelled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis. 8th ed. Gastroenterology. 94. 1988: 1368-1375
        • Ferry DM
        • Butt TJ
        • Broom MF
        • Hunter J
        • Chadwick VS
        Bacterial chemotactic oligopeptides and the intestinal mucosal barrier.
        Gastroenterology. 1989; 97: 61-67
        • Bjarnason I
        • Hayllar J
        • Macpherson AJ
        • Russell AS
        Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine.
        Gastroenterology. 1993; 104: 1832-1847
        • Krugliak P
        • Hollander D
        • Le K
        • Ma T
        • Dadufalza VD
        • Katz KD
        Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids.
        in: Influence of non-steroidal anti-inflammatory drugs. 8th ed. Gut. 31. 1990: 417-421
        • Sundquist T
        • Lindstrom F
        • Magnusson KE
        • Skoldstram L
        • Stjernstrom I
        • Tageson C
        Influence of fasting on intestinal permeability and disease activity in patients with rheumatoid arthritis.
        Scand J Rheumatol. 1982; 11: 33-38
        • Tageson C
        • Bengtsson A
        Intestinal permeability to different sized polyethylene glycols in patients with rheumatoid arthritis.
        Scand J Rheumatol. 1983; 12: 124-128
        • Siber GR
        • Mayer RJ
        • Levin MJ
        Increased gastrointestinal absorption of large molecules in patients after 5-fluorouracil therapy for metastatic colon carcinoma.
        Cancer Res. 1980; 40: 3430-3436
        • Pearson ADJ
        • Craft AW
        • Pledger JV
        • Eastham EJ
        • Laker MF
        • Pearson CS
        Small bowel function in acute lymphoblastic leukemia.
        Arch Dis Child. 1984; 59: 460-465
        • Pledger JV
        • Pearson ADJ
        • Craft AW
        • Laker MF
        • Eastham EJ
        Intestinal permeability during chemotherapy for childhood tumors.
        Eur J Pediatr. 1988; 147: 123-127
        • Selby PJ
        • Lopes N
        • Mundy J
        • Crofts M
        • Millar JL
        • McElwain TJ
        Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.
        Br J Cancer. 1987; 55: 531-533
        • Bjarnason I
        • Ward K
        • Peters TJ
        The leaky gut of alcoholism: possible route of entry for toxic compounds.
        Lancet. 1984; 1: 179-182
        • Robinson GM
        • Orrego H
        • Israel Y
        • Deveny P
        • Kapur BM
        Low-molecular weight polyethylene glycol as a probe of gastrointestinal permeability after alcohol ingestion.
        Dig Dis Sci. 1981; 26: 23-32
        • Smethurst P
        • Menzies IS
        • Levi AJ
        • Bjarnason I
        Is alcohol directly toxic to the small bowel mucosa?.
        Clin Sci. 1988; 75: 50P-51P
        • Aabakken L
        51Cr ethylenediaminetetraacetic acid absorption test.
        in: Methodological aspects. 8th ed. Scand J Gastroenterol. 24. 1989: 351-358
        • Worthington BS
        • Meserole L
        • Syrotuck JA
        Effect of daily ethanol ingestion on intestinal permeability to macromolecules.
        Dig Dis Sci. 1978; 23: 23-32
        • Cooper BT
        Tests of intestinal permeability in clinical practice.
        J Clin Gastroenterol. 1984; 6: 499-501
        • Bjarnason I
        • Peters TJ
        In vitro determination of intestinal permeability: demonstration of a persisting defect in patients with coeliac disease.
        Gut. 1984; 25: 145-150
        • Dawson DJ
        • Lobley RW
        • Burrows PC
        • Notman JA
        • Mahon M
        • Holmes R
        Changes in jejunal permeability and passive permeation of sugars in intestinal biopsies in coeliac disease and Crohn's disease.
        Clin Sci. 1988; 74: 427-431
        • Peter TJ
        • Bjarnason I
        Coeliac syndrome: biochemical mechanisms and the missing peptidase hypothesis revisited.
        Gut. 1984; 25: 913-918
        • Ferguson A
        • Arranz E
        • O'Mahoney S
        Clinical and pathological spectrum of coeliac disease—active, silent, latent, potential.
        Gut. 1993; 34: 150-151
        • Marsh MN
        • Bjarnason I
        • Ellis A
        • Baker R
        • Peters TJ
        Studies of intestinal lymphoid tissue XIV. HLA status, mucosal morphology, permeability and epithelial lymphoid populations in first degree coeliac sprue relatives.
        Gut. 1990; 31: 32-36
        • Hall EJ
        • Batt RM
        • Brown A
        Assessment of canine intestinal permeability, using 51CrEDTA.
        Am J Vet Res. 1989; 50: 2069-2074
        • Hall EJ
        • Batt RM
        Enhanced intestinal permeability to 51Cr-labelled EDTA in dogs with small intestinal diseases.
        J Am Vet Med Assoc. 1990; 196: 91-95
        • Jenkins RT
        • Goodacre RL
        • Rooney PJ
        • Bienenstock J
        • Sivakumaran J
        • Walker WHC
        Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400.
        Clin Biochem. 1986; 19: 298-302
        • Hollander D
        • Vadheim C
        • Brettholz E
        • Pattersen GM
        • Delahunty T
        • Rotter JI
        Increased intestinal permeability in patients with Crohn's disease and their relatives.
        Ann Intern Med. 1986; 105: 883-885
        • Magnusson KE
        • Sundquist T
        • Sjodahl R
        • Tageson C
        Altered intestinal permeability to low-molecular-weight polyethylene glycols (PEG 400) in patients with Crohn's disease.
        Acta Chir Scand. 1983; 149: 323-327
        • Heuman R
        • Sjodahl R
        • Tageson C
        Passage of molecules through the gastrointestinal tract: intestinal permeability to polyethylene glycol 1000 in patients with Crohn's disease.
        Acta Chir Scand. 1982; 148: 281-284
        • Olaison G
        • Sjodahl R
        • Tageson C
        Decreased gastrointestinal absorption of different-sized polyethylene glycols (PEG 1000) in Crohn's disease: a sign of jejunal abnormality.
        Acta Chir Scand. 1987; 153: 373-377
        • Olaison G
        • Leandersson P
        • Sjodahl R
        • Tageson C
        Intestinal permeability to polyethylene glycol 600 in Crohn's disease.
        in: Perioperative determination in a defined segment of the small bowel. 8th ed. Gut. 29. 1988: 196-199
        • Olaison G
        • Sjodahl R
        • Leandersson P
        • Tageson C
        Abnormal intestinal pattern in colonic Crohn's disease.
        in: Absorption of low molecular weight polyethylene glycols after oral and colonic load. 8th ed. Scand J Gastroenterol. 24. 1989: 571-576
        • Olaison G
        • Sjodahl R
        • Tageson C
        Abnormal intestinal permeability in Crohn's disease.
        in: A possible pathogenic factor. 8th ed. Scand J Gastroenterol. 25. 1990: 321-328
        • Teahon K
        • Smethurst P
        • Levi AJ
        • Menzies IS
        • Bjarnason I
        Intestinal permeability in patients with Crohn's disease and their first degree relatives.
        Gut. 1992; 33: 320-323
        • Ruttenberg D
        • Young GO
        • Wright JP
        • Isaacs S
        PEG 400 excretion in patients with Crohn's disease, their first degree relatives, and healthy volunteers.
        Dig Dis Sci. 1992; 37: 705-708
        • Munkholm P
        • Langholz E
        • Hollander D
        • Thornberg K
        • Orholm M
        • Katz KD
        • Binder V
        Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives.
        Gut. 1994; 35: 68-72
        • Ainsworth M
        • Eriksen J
        • Rasmussen JW
        • Schaffalitzkydemuckadel OB
        Intestinal permeability of 51Cr-labelled ethylenediaminetetraacetic acid in patients with Crohn's disease and their first degree relatives.
        Scand J Gastroenterol. 1989; 24: 993-998
        • Katz KD
        • Hollander D
        • Vadheim CM
        • McElree C
        • Delahunty T
        • Dadufalza VD
        • Krugliak P
        • Rotter JI
        Intestinal permeability in patients with Crohn's disease and their healthy relatives.
        Gastroenterology. 1989; 97: 927-931
        • May GR
        • Sutherland LR
        • Meddings JB
        Is small intestinal permeability really increased in relatives of patients with Crohn's disease?.
        Gastroenterology. 1993; 104: 1627-1632
        • Hollander D
        Permeability in Crohn's disease—altered barrier function in healthy relatives?.
        Gastroenterology. 1993; 104: 1848-1851
        • Juby LD
        • Rothwell J
        • Axon ATR
        Cellobiose/mannitol sugar test: a sensitive tubeless test for coeliac disease.
        in: Results on 1010 unselected patients. 8th ed. Gut. 30. 1989: 476-480
        • Isolauri E
        • Juntunen M
        • Wirens S
        • Vuirien P
        • Koivula T
        Intestinal permeability changes in acute gastroenteritis: Effects of clinical factors and nutritional management.
        J Pediatr Gastroenterol Nutr. 1989; 8: 466-473
        • Molyneux M
        • Looareesuwan S
        • Menzies IS
        • Grainger SL
        • Phillips RE
        • Wattanagoon Y
        • Thompson R
        • Warrell DA
        Reduced hepatic blood flow and intestinal malabsorption in severe falciparum malaria.
        Am J Trop Med Hyg. 1989; 40: 470-476
        • Northrop CA
        • Lunn PC
        • Mainwright M
        • Evans J
        Plasma albumin concentrations and intestinal permeability in Bangladeshi children infected with ascaris lumbricoides.
        Trans R Soc Trop Med Hyg. 1987; 81: 811-815
        • Lawson GR
        • Nelson R
        • Laker MF
        • Ghatei MA
        • Bloom SR
        • Aynsley GA
        Gut regulatory peptides and intestinal permeability in acute infantile gastroenteritis.
        Arch Dis Child. 1992; 67: 272-276
        • Parrili G
        • Cumo R
        • Nardone G
        • Maio G
        • Izzo CM
        • Budillon G
        Investigation of intestinal function during acute viral hepatitis using combined sugar load.
        Gut. 1987; 28: 1439-1444
        • Strobel S
        • Byrdon WG
        • Ferguson A
        Cellobiose/mannitol sugar permeability test compliments biopsy histopathotogy in clinical investigations of the jejunum.
        Gut. 1984; 25: 1241-1246
        • Juby LD
        • Dixon MF
        • Axon ATR
        Abnormal intestinal permeability and jejunal morphometry.
        J Clin Pathol. 1987; 40: 714-718
        • Stintzing G
        • Johansen K
        • Magnusson KE
        • Svensson L
        • Sundquist T
        Intestinal permeability in small children during and after Rotavirus diarrhoea assessed with different-sized polyethylene glycols (PEG 400 and PEG 1000).
        Acta Pediatr Scand. 1986; 75: 1005-1009
        • Serrander R
        • Magnusson KE
        • Sundquist T
        Acute infection with Giardia lamblia and Rotavirus decrease intestinal permeability to low molecular weight polyethylene glycols (PEG 400).
        Scand J Infect Dis. 1984; 16: 339-344
        • Serrander R
        • Magnusson KE
        • Kihlstrom E
        • Sundquist T
        Acute Yersinia infection in man increases intestinal permeability for low-molecular weight polyethylene glycols (PEG 400).
        Scand J Infect Dis. 1989; 18: 409-413
        • Lahesmaa-Rantala R
        • Magnusson KE
        • Gransfors K
        • Leino R
        • Sundquist T
        • Toivanen A
        Intestinal permeability in patients with Yersinia triggered reactive arthritis.
        Ann Rheum Dis. 1991; 50: 91-94
        • Sundquist T
        • Magnusson KE
        • Larsson L
        • Tageson C
        • Backman L
        • Nordenvall B
        Reduced intestinal permeability to low-molecular-weight polyethylene glycols (PEG 400) in patients with jejunoileal bypass.
        Acta Chir Scand. 1984; 150: 567-571
        • Brunser O
        • Eidelman S
        • Kupstein FA
        Intestinal morphology of rural Haitians.
        in: A comparison between overt tropical sprue and asymptomatic subjects. 8th ed. Gastroenterology. 58. 1970: 655-668
        • Cook CG
        • Menzies IS
        Intestinal adsorption and unmediated permeation of sugars in post-infective tropical malabsorption.
        Digestion. 1986; 33 (tropical sprue): 109-116
        • Pignata C
        • Budillon G
        • Monaco G
        • Nani E
        • Cuomo R
        • Parrilli G
        • Ciccimarra F
        Jejunal bacterial overgrowth and intestinal permeability in children with immunodeficiency syndromes.
        Gut. 1990; 31: 879-882
        • Teahon K
        • Webster AD
        • Price AB
        • Weston J
        • Bjarnason I
        Studies on the enteropathy associated with primary hypogammaglobulinaemia.
        Gut. 1994; 35: 1244-1249
        • Ott M
        • Lembcke B
        • Staszewski S
        • Helm EB
        • Caspary WF
        Intestinal permeability in patients with acquired immunodeficiency syndrome (AIDS).
        Kiln Wochenschr. 1991; 69: 715-721
        • Lim SG
        • Menzies IS
        • Lee CA
        • Johnson MA
        • Pounder RE
        Intestinal permeability and function in patients infected with human immunodeficiency virus.
        Scand J Gastroenterol. 1993; 28: 573-580
        • Keating J
        • Bjarnason I
        • Somasundaram S
        • Macpherson A
        • Francis N
        • Price AB
        • Sharpstone D
        • Smithson J
        • Menzies IS
        • Gazzard IS
        Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV infected patients and their relation to diarrhoea.
        Gut. 1995; 36 (in press)
        • Atherton DJ
        Allergy and atopic eczema II.
        Clin Exp Dermatol. 1981; 6: 317-325
        • Bjarnason I
        • Goolamali SK
        • Levi AJ
        • Peters TJ
        Intestinal permeability in patients with atopic eczema.
        Br J Dermatol. 1985; 112: 291-297
        • Barba A
        • Schena D
        • Andreaus MC
        • Faccini G
        • Pasini F
        • Brocco G
        • Cavallini G
        • Scuro LA
        • Chieregato GC
        Intestinal permeability in patients with atopic eczema.
        Br J Dermatol. 1989; 120: 71-75
        • Scadding C
        • Bjarnason I
        • Brostoff J
        • Levi AJ
        • Peters TJ
        Intestinal permeability to 51Cr-labelled ethylenediaminetetraacetate in food-intolerant subjects.
        Digestion. 1989; 42: 104-109
        • Ukabam SO
        • Mann RJ
        • Cooper BT
        Small intestinal permeability to sugars in patients with atopic eczema.
        Br J Dermatol. 1984; 110: 649-652
        • Newton JA
        • Maxton DG
        • Bjarnason I
        • Reynolds AP
        • Menzies IS
        Intestinal permeability in atopic eczema.
        Clin Sci. 1984; 67 (abstr): 64P
        • Hamilton I
        • Fairris GM
        • Rothwell J
        • Cunliffe WJ
        • Dixon MF
        • Axon ATR
        Small intestinal permeability in dermatological disease.
        Q J Med. 1985; 56: 559-567
        • Paganelli R
        • Fagiolo U
        • Cancian M
        • Sturniolo GC
        • Scala E
        • D'Offizi GP
        Intestinal permeability in irritable bowel syndrome.
        in: Effect of diet and sodium chromoglycate administration. 8th ed. Ann Allergy. 64. 1990: 377-380
        • Andre C
        • Andre F
        • Colin L
        • Cavagna S
        Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium chromoglycate.
        Ann Allergy. 1987; 59: 127-130
        • Andre F
        • Andre C
        • Feknous M
        • Colin L
        • Cavagna S
        Digestive permeability to different-sized molecules and to sodium cromoglycate in food allergy.
        Allergy Proc. 1991; 12: 293-298
        • Dumont GCL
        • Beach RC
        • Menzies IS
        Gastrointestinal permeability in food-allergic eczematous children.
        Clin Allergy. 1984; 14: 55-59
        • Barau E
        • Dupont C
        Modifications of intestinal permeability during food provocation procedures in pediatric irritable bowel syndrome.
        J Pediatr Gastroenterol Nutr. 1990; 11: 72-77
        • Pike MG
        • Heddle RJ
        • Boulton P
        • Turner MW
        • Atherton DJ
        Increased intestinal permeability in atopic eczema.
        J Invest Dermatol. 1986; 86: 101-104
        • Pike MG
        • Riches P
        • Atherton DJ
        Fecal α1-antitrypsin concentration and gastrointestinal permeability to oligosaccharides in atopic dermatitis.
        Pediatr Dermatol. 1989; 6: 10-12
        • Schrander JJP
        • Unsalan-Hooyen RWM
        • Forest PP
        • Jansen J
        [51Cr]EDTA intestinal permeability in children with cow's milk intolerance.
        J Pediatr Gastroenterol Nutr. 1990; 10: 189-192
        • Hamilton I
        • Hill A
        • Rose B
        • Boucher IAD
        • Forsyth JS
        Small intestinal permeability in pediatric clinical practice.
        J Pediatr Gastroenterol Nutr. 1987; 6: 697-701
        • Dupont C
        • Barau E
        • Molkhou P
        • Raynaud F
        • Barbet JP
        • Dehennin L
        Food-induced alteration in intestinal permeability in children with cow's milk-sensitive enteropathy and atopic dermatitis.
        J Pediatr Gastroenterol Nutr. 1989; 8: 459-465
        • Weaver LT
        The impact of milk and weaning diet on gastrointestinal permeability in English and Gambian infants.
        Trans R Soc Trop Med Hyg. 1988; 82: 784-789
        • Jackson PG
        • Baker RWR
        • Lessof HM
        • Ferrett J
        • MacDonald DM
        Intestinal permeability in patients with eczema and food allergy.
        Lancet. 1981; 1: 1285-1286
        • Falth-Magnusson K
        • Kjellman NIM
        • Magnusson KE
        • Sundquist T
        Intestinal permeability in healthy and allergic children before and after sodium-chromoglycate treatment assessed with different sized polyethylene glycols (PEG 400 and 1000).
        Clin Allergy. 1984; 14: 277-286
        • Falth-Magnusson K
        • Kjellman NIM
        • Sundquist T
        • Magnusson KE
        Gastrointestinal permeability in atopic and non-atopic mothers, assessed with different sized polyethylene glycols (PEG 400 and PEG 1000).
        Clin Allergy. 1985; 15: 565-570
        • Falth-Magnusson K
        • Kjellman NIM
        • Odelram H
        • Sundqvist T
        • Magnusson KE
        Gastrointestinal permeability in children with cow's milk allergy: effect of milk challenge and sodium chromoglycate as assessed with polyethylene glycols (PEG 400 and PEG 1000).
        Clin Allergy. 1986; 16: 543-551
        • Moller C
        • Magnusson KE
        • Sundquist T
        • Stenling R
        • Bjorksten B
        Intestinal permeability as assessed with polyethylene glycols in birch pollen allergic children undergoing oral immunotherapy.
        Allergy. 1986; 41: 280-285
        • Maran AGD
        • Ferguson A
        • Rutherford D
        Small bowel permeability in patients with nasal polyposis.
        Rhinology. 1986; 24: 195-198
        • Selby P
        • McElwain TJ
        • Crofts M
        • Lopes N
        • Mundy J
        51CrEDTA test for intestinal permeability.
        Lancet. 1984; 2 (letter): 39
        • Mansi J
        • Ellis E
        • Viner C
        • Mundy J
        • Smith T
        • Millar J
        • Milan S
        • Gore M
        • Cunningham D
        Gut protection by Cyclophosphamide “priming” in patients receiving high-dose melphalan—effect of drug scheduling.
        Cancer Chemother Pharmacol. 1992; 30: 149-151
        • Grant D
        • Wall W
        • Mimeault R
        • Zhong R
        • Ghent C
        • Garcia B
        • Stiller C
        • Duff J
        Successful small bowel/liver transplantation.
        Lancet. 1990; 335: 181-184
        • Grant D
        • Hurlbut D
        • Zhong R
        • Wang PZ
        • Chen HF
        • Garcia B
        • Behme R
        • Stiller C
        • Duff J
        Intestinal permeability and bacterial translocation following small bowel transplantation in the rat.
        Transplantation. 1991; 52: 221-224
        • Sigalet DL
        • Kneteman NM
        • Fedorak RN
        • Kizilisik AT
        • Thomson AB
        Intestinal function following allogenic small intestinal transplantation in the rat.
        Transplantation. 1992; 53: 264-271
        • Lifschitz CH
        • Mahoney DH
        Low-dose methotrexate-induced changes in intestinal permeability determined by polyethylene glycol polymers.
        J Pediatr Gastroenterol Nutr. 1989; 9: 301-306
        • Cooper BT
        • Ukabam SO
        • O'Brien IAD
        • Hara JPO
        • Corrall RJM
        Intestinal permeability in diabetic diarrhoea.
        Diabet Med. 1987; 4: 49-52
        • Wallaert B
        • Colombel JF
        • Adenis A
        • Merchandise X
        • Hallgren R
        • Janin A
        • Tonnel AB
        Increased intestinal permeability in active pulmonary sarcoidosis.
        Am Rev Respir Dis. 1992; 145: 1440-1445
        • Prytz H
        • Benoni C
        • Tageson C
        Does smoking tighten the gut?.
        Scand J Gastroenterol. 1989; 24: 1084-1088
        • Leclercq-Foucart J
        • Forget P
        • Sodoyez-Gouffaux F
        • Zappitelli A
        Intestinal permeability to 51CrEDTA in children with cystic fibrosis.
        J Pediatr Gastroenterol Nutr. 1986; 5: 384-387
        • Leclercq-Foucart J
        • Forget P
        • Van Cutsem JL
        Lactulose-rhamnose intestinal permeability in children with cystic fibrosis.
        J Pediatr Gastroenterol Nutr. 1987; 6: 66-70
        • Maxton DG
        • Menzies IS
        • Slavin B
        • Thompson RPH
        Small intestinal function during enteral feeding and starvation in man.
        Clin Sci. 1989; 77: 401-406
        • Lunn PG
        • Northrop CA
        • Downes RM
        Recent developments in the nutritional management of diarrhoea. 2. Chronic diarrhoea and malnutrition in the Gambia: studies on intestinal permeability.
        Trans R Soc Trop Med Hyg. 1991; 85: 8-11
        • Sullivan PB
        • Lunn PG
        • Northrop CC
        • Crowe PT
        • Marsh MN
        • Neale G
        Persistent diarrhea and malnutrition—the impact of treatment on small bowel structure and permeability.
        J Pediatr Gastroenterol Nutr. 1992; 14: 208-215
        • Budillon G
        • Parilli G
        • Capuano G
        • Mazzacca G
        • Menzies IS
        The cholecystokihin effect on human intestinal permeability: influence of chenodeoxycholic and ursodeoxycholic acid administration.
        Digestion. 1982; 24: 274-280
        • Erickson RA
        • Epsten RM
        Oral chenodeoxycholic acid increases small intestinal permeability to lactulose in humans.
        Am J Gastroenterol. 1988; 83: 541-544
        • O'Dwyer SJ
        • Michie HR
        • Ziegler TR
        • Revhaug A
        • Smith RJ
        • Wilmore DW
        A single dose of endotoxin increases intestinal permeability in healthy humans.
        Arch Surg. 1988; 123: 1459-1464
        • Deitz EA
        Intestinal permeability is increased in burn patients shortly after injury.
        Surgery. 1990; 102: 411-412
        • Ziegler TR
        • Smith RJ
        • O'Dwyer ST
        • Demling RH
        • Wilmore DW
        Increased intestinal permeability associated with infection in burn patients.
        Arch Surg. 1988; 123: 1313-1319
        • LeVoyer T
        • Cioffi WG
        • Pratt L
        • Shippee R
        • McManus WF
        • Mason AD
        • Pruitt BA
        Alterations in intestinal permeability after thermal injury.
        Arch Surg. 1992; 127: 26-29
        • Magnusson M
        • Magnusson KE
        • Sundqvist T
        • Denneberg T
        Urinary excretion of differently sized polyethylene glycols after intravenous administration in uremic and control rats: effects of low- and high-protein diets.
        Nephron. 1990; 56: 312-316
        • Magnusson M
        • Magnusson KE
        • Sundqvist T
        • Denneberg T
        Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets.
        Nephron. 1990; 56: 306-311
        • Wood NC
        • Hamilton I
        • Axon ATR
        • Khan SA
        • Quirke P
        • Mindham RH
        • Mcguigan K
        • Prison HM
        Abnormal intestinal permeability.
        in: An aetiological factor in chronic psychiatric disorders?8th ed. Br J Psychiatry. 150. 1987: 853-856
        • Lambert MT
        • Bjarnason I
        • Connelly J
        • Crow TJ
        • Johnston EL
        • Peters TJ
        • Smethurst P
        The gastrointestinal permeability of schizophrenia patients.
        Br J Psychiatry. 1989; 155: 619-622
        • Van Der Meer SB
        • Forget PP
        • Heidendal GA
        Small bowel permeability to 51Cr-EDTA in children with recurrent abdominal pain.
        Acta Paediatr Scand. 1990; 79: 422-426
        • Saweirs WM
        • Andrews DJ
        • Low-Beer TS
        The double sugar test of intestinal permeability in the elderly.
        Age Ageing. 1985; 14: 312-315
        • Ma TY
        • Hollander D
        • Dadufalza V
        • Krugliak P
        Effect of ageing and caloric restriction on intestinal permeability.
        Exp Gerontol. 1992; 27: 321-333
        • Budillon G
        • Parrilli G
        • Pacella M
        • Cuomo R
        • Menzies IS
        Investigation of intestine and liver function in cirrhosis using combined sugar oral loads.
        J Hepatol. 1985; 1: 513-524
        • Wicks C
        • Somasundaram S
        • Bjarnason I
        • Menzies IS
        • Routley D
        • Potter D
        • Tan MC
        • Williams R
        Comparison of enteral feeding and total parenteral nutrition after liver transplantation.
        Lancet. 1993; 344: 340-387
        • Ohri SK
        • Somasundaram S
        • Koak Y
        • Macpherson A
        • Keogh BE
        • Taylor KM
        • Menzies IS
        • Bjarnason I
        The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass.
        Gastroenterology. 1994; 106: 318-323
        • Roumen RM
        • van der Vliet JA
        • Wevers RA
        • Goris RJ
        Intestinal permeability is increased after major vascular surgery.
        J Vasc Surg. 1993; 17: 734-737
        • Harris CE
        • Griffiths RD
        • Freestone N
        • Billington D
        • Atherton ST
        • Macmillan RR
        Intestinal permeability in the critically ill.
        Intensive Care Med. 1992; 18: 38-41
        • Oktedalen O
        • Lunde OC
        • Opstad PK
        • Aabakken L
        • Kvemebo K
        Changes in the gastrointestinal mucosa after long-distance running.
        Scand J Gastroenterol. 1992; 27: 270-274
        • Berant M
        • Khourie M
        • Menzies IS
        Effect of iron deficiency on small intestinal permeability in infants and young children.
        J Pediatr Gastroenterol Nutr. 1992; 14: 17-20