Faecal Alpha-1-Antitrypsin and Excretion of Tllndium Granulocytes in Assessment of Disease Activity in Chronic Inflammatory Bowel Diseases

Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from Gut, 1987, 28, 386-393

Faecal alpha-1-antitrypsin and excretion of tllndium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases

W FISCHBACH, W BECKER, J MOSSNER, W KOCH, AND C REINERS From the Medizinische Poliklinik and Department ofNuclear Medicine, University ofWurzburg, FR Germany

SUMMARY Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (ct-AT) stool concentration and a1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum cta-AT, faecal excretion and clearance of a,-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of a,-AT faecal excretion and clearance with the faecal excretion of "'In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of a,-AT does not depend on mucosal inflammation only, but may be influenced by other factors. http://gut.bmj.com/

Intestinal protein loss seems to be common feature in loss was related to intestinal inflammation`9 and the chronic inflammatory bowel diseases such as Crohn's extent of intestinal damage.' The aim of this pro- disease or ulcerative colitis. For many years protein spective study, therefore, was to compare faecal on September 26, 2021 by guest. Protected copyright. loss into the gastrointestinal tract could be only excretion and clearance of a,-AT as parameters of determined by using radiolabelled serum proteins intestinal protein loss with the faecal excretion of like "Cr-albumin. Bernier' and Crossley2 introduced "'In-labelled granulocytes as parameter of bowel the faecal excretion of alpha-1-antitrypsin (at,-AT) as inflammation in patients with chronic inflammatory a reliable and easy method for detecting a protein bowel diseases. Additionally both methods were losing enteropathy. Several authors have shown that compared with clinical indices, serum laboratory a,-AT clearance reflected intestinal protein loss just findings, and morphological parameters. as well as the ~'Cr-albumin method.' Quantification of the faecal excretion of intra- Methods venously infused autologous "'In-oxin-labelled white blood cells seems to be a highly specific parameter of PATI ENTS bowel inflammation.? We and others found that Forty three patients with chronic inflammatory measuring faecal excretion of "'In-labelled granu- bowel diseases (33.3±15, range 13-78 years, 21 locytes was a reliable parameter to distinguish active women, 22 men) were investigated. Thirty one from inactive inflammatory bowel disease.7' Pre- patients had Crohn's disease, eight ulcerative colitis viously published data suggested that enteric protein and four unspecific colitis. The diagnosis of Crohn's disease was based on the criteria published by the Address for corrcspondencc: Dr W Fischbach. Medizinische Poliklinik. European Cooperative Crohn's disease Study Group University of Wurzhurg. Klinikstrassc 8. Wurzhtirg87(. FRG. (ECCDS)." Ulcerative colitis was characterised by Received tor publication 23 July 1986. typical endoscopical and histological features and the 386 Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from Faecal alpha-i -antitrypsin in chronic inflammatory bowel diseases 387 characteristic localisation pattern. Unspecific colitis Faecal at,-AT was determined by radial immuno- was defined as colitis lacking any of the above diffusion using commercially available partigen mentioned criteria for Crohn's disease or ulcerative plates (LC-partigen, Behring AG, FRG). According colitis. Furthermore infectious causes have been to the method of Crossley and Elliott' an aliquot of excluded. As well as small bowel radiography exami- lyophilised stool (250 mg) was extracted with 5 ml nation and coloileoscopy, routine laboratory 0 9% saline by gently mixing over 30 minutes at 220C. parameters, orosomucoid, serum at,-AT and clinical After centrifugation (12 000 g for 15 minutes at 4°C) indices (CDAI, AI, Truelove index)"'-" were evalu- 5 Rl of the supernatant were placed into the wells of ated in all patients. Alpha-1-antitrypsin stool concen- partigen plates. The diameter of the precipitating tration could be measured in 36 patients. Because of rings was measured after 72 hours. As control served unreliable stool collection in two cases only 34 a reference curve with serum of known a,-AT patients were available for clearance determination. concentration. Faecal et,-AT was expressed in mg In 27 patients the percentage of faecal excretion of a,-AT/g dry stool weight. "'In-labelled autologous granulocytes could be Median daily stool weight was determined from studied simultaneously. All stool and blood collec- the four days stool collection and a,-AT clearance tions were done on the same day. Faecal excretion of was calculated by the formula: C=FxW/P (C= "''In and ai-AT were measured in identical stool clearance, F=faecal at,-AT [mg/g stool], W=daily samples. All other investigations such as radio- stool weight [g] and P=serum a,-AT [mg/dll). graphic and endoscopy were carried out within eight days. PER CENT EXCRETION OF M'IN-OXIN Patients with chronic inflammatory bowel diseases Isolation of white blood cells and labelling of were classified as 'active' if the following criteria were granulocyte preparations with .'.In-oxin was carried fulfilled: for all cases of chronic inflammatory bowel out as previously described.` ".'In-activity of stool diseases histologically diagnosed acute bowel inflam- samples was measured in a gamma-counter and mation; additionally for Crohn's disease CDAI>150 expressed as per cent of the reinjected dose (4.2 and/or activity index van Hees>100; for ulcerative MBq=250 [tCi) after decay correction. colitis 'severe' or 'moderately severe' according to

the Truelove index;'4 and for unspecific colitis clinical STATISTICAL ANAL YSIS http://gut.bmj.com/ signs and laboratory parameters indicating acute Statistical analysis was undertaken using the inflammation. arithmetic mean and its standard error of the mean In addition four patients with Crohn's disease (x±SEM) and the Spearman's rank correlation could be studied twice at different states of their coefficient. All correlation coefficients with p<005 disease. were considered significant. Using a rank variance Twenty one healthy volunteers (24±2.7, range analysis according to Kruskall and Wallis significance 21-33 years, 10 women, 11 men) and eight patients was considered on a level of a=0 05. with non-inflammatory bowel diseases (irritable on September 26, 2021 by guest. Protected copyright. bowel syndrome n=7, inactive Whipple's disease Results n= 1, 43.4±17 1, range 21-68 years, two women, six men) served as controls. All of them completed a Serum a,-AT was significantly higher (u<0.001) in reliable stool collection. "'In-faecal-excretion was patients with chronic inflammatory bowel diseases only available in patients with non-inflammatory than in normal controls or in patients with non- bowel diseases and because of radiation safety regu- inflammatory bowel diseases (Table, Fig. 1). The lations not in volunteers. patients with active disease had significantly (a<0.05) higher values than those with inactive SERUM LABORATORY PARAMETERS disease (Table, Fig. 1). Alpha-1-antitrypsin serum Erythrocyte sedimentation rate was measured in the concentrations correlated with ESR (r=0.67, usual way, serum albumin was determined by auto- p<0001), serum albumin (r=-0(47, p<0.01l), mated analysis using the bromcresol-green method. orosomucoid (r=0.49, p<0001) and activity index Orosomucoid (human acid a,-glycoprotein) was van Hees (r=0.74, p<0 001), but not with CDAI. measured by radial immunodiffusion using partigen Alpha-1-antitrypsin stool concentration was sig- plates (Behring AG, FRG). nificantly (a<0 001) raised in patients with chronic inflammatory bowel diseases compared with normal DETERMINATION OF ALPHAj-ANTITRYPSIN controls or patients with non-inflammatory bowel Serum at,-AT concentration was measured by laser diseases (Table, Fig. 2). Patients with active disease nephelometry with a monospecific antiserum against showed higher al-AT concentrations than those with a,-AT (Behring AG, FRG) and expressed in mg/dl. inactive disease (Table, Fig. 2), but the difference Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from

388 Fischbach, Becker, Mossner, Koch, and Reiners

Taible Serum act-A T(mgldl), Jaecal at -A T(mglg), ax-A Tclearance (mild) andpercentagefaecal excretion (%) of'...In labelled granulocytes in patients with chronic inflammatory bowel diseases (CIBD), non-inflammatory bowel diseases (NIBD) and in normal controls

Serun ct-A T Faecal(ux-A T (xi-A Tclearan7ce Faecalexcretion (ingl/dl) (inglg) (itild) (%) CIBD 377+50-4 1-50±0)- 17 115-7±22-4 Active diseisc 423.8±29.4 1-65+±033 92+41-9 21-7+4-9 Inzactivc discasc 239-9+ 13-6 1-43+0-18 117-9+20-8 2-1+±0-4 Previous resection 299+28-5 148+0-42 231 +91-1 No resection 30)3+ 16-9 1-56+0-21 73-3+ 108 NIBD 238+ 11 0-60+0-21 49+16 1.5+±0-5 Normal controls 241 ± 11 0-58±0-11 39+8-4

947 947 J597 s597 500

0; 10 0 400t http://gut.bmj.com/

0 0

E 0% 0 300t E 0 20 0

0 4) on September 26, 2021 by guest. Protected copyright.

10 0% c I 0

CLc$- 5- 0

w- 200t

0 0

1cJU'

OIL n=21 n=43 n=21 n=22 n=8 Normal FInflammatory Inactive a Non inflammatory controls 1boweledisease e t bowel diseases Fig. 1 ct -A Tserum concentration (mgldl) in normal controls, patients with inactive and active inflammatory bowel diseases andpatients with non-inflammatory bowel diseases. Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from Faecal alpha-I -antitrypsin in chronic inflammatory bowel diseases was not statistically significant. Alpha-l-antitrypsin There was a significant difference (s<().()1) in stool concentrations were higher in patients with a al,-AT clearance between patients with chronic combined involvement of small and large bowel inflammatory bowel diseases and normal controls or (1.7±0.4 ng/mg, n=13) compared with those who patients with non-inflammatory bowel diseases had only the ileum (1.4±0.4 ng/mg, n=8) or the (Table, Fig. 3). Patients with active disease did not colon (1.4±0.2 ng/mg, n=15) involved. There was differ from those with inactive disease (Table, Fig. however, no clear relationship between faecal a,-AT 3). Alpha-l-antitrypsin clearance did not correlate and the extent of inflamed bowel. Some patients with with ESR, serum albumin, orosomucoid, activity acute inflammation over a small segment showed index van Hees, or CDAI. No relationship between higher faecal ca-AT concentration compared with at,-AT clearance and site or extent of bowel inflam- those with a more extensive involvement. Further- mation could be established. There was however, more no correlation of faecal al,-AT with ESR, serum a tendency towards a higher a,-AT clearance in albumin, orosomucoid, activity index van Hees, or patients with previous resections compared with CDAI could be found. unresected patients (Table, Fig. 4). These findings

\,! 6,2 6, 2

4-0-

mn 3.0 http://gut.bmj.com/ E

0 C 0 S 1-C .. 0@ a 20- 0

0 -I on September 26, 2021 by guest. Protected copyright. c a0- 1 0O 0 S.. b 0O 0" *00 0 S. 00 00 *-. 1.04 0@ .0000 0 *- 0 0* 0* 0 S.. . S 0 {i I*- S S0 0O S S

S 0 0000w - 0 n =19 n=36 n= 18 n=18 n =8 Normal Non inflammatory controls bowel diseases Inactive Active bowel diseases ______~~~~~~~~~ Fig. 2 u-A Tstool concentration (mg/g) in normal controls, patient.s with inactive and active inflammatorv bowel di.sease.s and patients with non-inflammatory bowel diseases. Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from 390 Fischbach, Becker, M(issner, Koch, and Reiniers were independent of the actual inflammatory ac- Serial studies were possible in 4 patients with tivity. These two groups did not differ from each Crohn's disease (Fig. 6). Two of them (RK, StCh) other if their a,-AT serum or stool concentrations showed a decrease of disease activity, one patient were compared (Table, Fig. 4). (El) was stable and another one (MB) developed The percentage faecal excretion of "'In labelled intestinal fistulae (Fig. 6). The individual studies granulocytes was significantly (a<0(00l) raised in showed a parallel decrease or increase of serum patients with active inflammatory bowel disease at,-AT and percentage faecal excretion of ..'In compared with patients with inactive disease or non- labelled granulocytes with disease activity whereas inflammatory bowel diseases (Table, Fig. 5). All but faecal a,-AT took an obviously different course in at one 'active' patient excreted more than 4% (Fig. 5). least two patients (StCh, MB, Fig. 6). There was a good correlation between the percentage faecal excretion and ESR (r=0(62, p<0()(l), serum Discussion albumin (r= -0-44, p<0.001 ), orosomucoid (r=0.51, p<0.01), serum a,-AT (r=0(63, p<0l001) In accordance with previously published data"s and activity index van Hees (r=0 65, p<0001), but serum a,-AT was significantly raised in patients no statistically significant correlation with a,-AT suffering from chronic inflammatory bowel diseases stool concentration or a,-AT clearance. compared with patients with non-inflammatory

705 \/ ,705

400 - http://gut.bmj.com/

E 300- 0

0 0 0 CJcs U

Q._ 1- 0

cs0 0 0

100

00.2 00 Og @0 00 0.0 0 .00 00 1. 0 0.I.| S

0 S 0 *- nf . - *- n=l9 n=34 n=18 n=16 n=5

Normalt Inflammatory I Non inflammatory controls 1Lbowetdiseases Inactive Active bowel diseases Fig. 3 a,-A Tcelaraince (illd) in normal controls, patients itl/ ina(cti,e anld acl,tvte inflammatory boweldiseases andpatients wit/i non-inflait?iiniatori' bowel (liseases. Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from

Faecal alpha-l-antitrypsin in chronic inflammatory boweI1 diseases 391

, 705 s,6 2 a,-AT stool concentration (Fig. 2). Furthermore 400t 4.0 faecal a,-AT was obviously lower in our patients with chronic inflammatory bowel diseases compared with those of Thomas' and Meyers.2 Considering . identical stool preparations and similar at,-AT stool concentrations in the control subjects we believe that

300 0 30 selection of patients rather than a technical problem V may explain this discrepancy. Our percentage of 0 E J patients with high disease activity was relatively low '0 as our group mainly consisted of outpatients. L< Alpha-1-antitrypsin clearance was significantly a U ** 0 'S higher in our patients with chronic inflammatory 2.0 sa bowel diseases but contrary to Karbach and 0 Bernierl' c 00 an unequivocal overlap with our controls was evident . 0 ~0 (Fig. 3). Alpha-1-antitrypsin clearance of our c 0 patients was quite similar to their patient data

*-* I 0 whereas our normal controls showed distinctly higher b1 100.1- 10 59e2 0 soj 0** . - -~~~~~V n=27 n=7 n=29 n=7 No Prior No Prior Resection Resection 0 Fig. 4 al-A Tclearance (mlld) and a,-A Tstool concentration (mglg) in patients with CIBD with or without 30' http://gut.bmj.com/ previous resections. c bowel diseases or normal controls (Table, Fig. 1). 0 U 0 Active and inactive inflammatory disease were X clearly separated. Serum al-AT indicated the S. systemic inflammatory activity similarly to clinical ~20. L- indices or other laboratory parameters and run on September 26, 2021 by guest. Protected copyright. parallel to the course of disease (Fig. 6). U Beeken et al"' found that intestinal protein loss UC- reflects well the extent of inflamed bowel segments. Their results were based on intestinal protein clearance utilising `Cr-albumin or "Cr-chloride. Crossley . and Elliott2 overcame the disadvantage using radio- 10. labels and described faecal a,-AT as a reliable test for 0 protein losing enteropathies, suitable for clinical S . routine because of its simplicity. Several authors 0 have shown that there is a good correlation between I cal-AT clearance and `Cr-albumin.' In chronic S inflammatory bowel diseases faecal excretion and clearance of al-AT seem to be objective parameters ti for the grading of intestinal inflammation."9 120 n= 15 n=12 In accordance with Karbach,' Thomas," and Meyers" our results indicate that faecal ea,-AT is IInactive Active significantly raised in chronic inflammatory bowel inflammatory | diseases compared with normal controls or non- I boweI diseasesl 1' inflammatory bowel diseases (Fig. 2). Contrary to Fig. 5 Percentagefaecal excretion (%) of' "In labelled Thomas et al,' however, active disease could not be granulocytes in inactive and active inflammatory bowel clearly separated from inactive disease by measuring disease. Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from 392 Fi.schbach, Becker, Mossner, Koch, and Reiners

RK, ,21y StCh, ,34y EJ, ?,25y MB, a,46y 4 4 62, p _p .2- I 60- 600 ° c D. 3 07 5Q- I 2 `, -500 n 6 I 'a D c 40 fin 400 0 0 tD I - 0 2 -300 3 U 30 Id I. -1 3 a 20 / ta 200 2 /~~~~~~~~~~~~~~ 1-1 /~~~~~~~~~~~~~~~ a L 10 4?~~~~~~~~~~~~~~~~ O -100

ate 6/84 9/84i 4/84 11/84 i 5/84 10/84 3/84 12/84 "01 t 1 Resection Fistulae ESR (1 1 105 2 j 25 12 46 50 25 25 Orosomucoid(mg/dl),336 94 1214 94 1197 177 F 142 174 Ai.v. Hees 184 98 |142 130 i1133 134 178 156 Diseose activity jI1f* (+)Fi ! ______Fig. 6 Percentagefaecal excretion (%) of "In-oxin labelled granulocytes, au -A Tstool (mglg) and serum (mgldl) concentration compared with ESR, orosomucoid, A land disease activity infourpatients with Crohn 's disease at different states oftheir disease. http://gut.bmj.com/ values. Neither faecal ct,-AT nor a,-AT clearance age of faecal excretion rapidly reflects any changes in correlated with ESR, serum albumin, serum,at1-AT, inflammatory activity and is not masked by medical orosomucoid, clinical indices or sites and extent of treatment.8 With one exception we found a clear inflammation as diagnosed by radiological and endo- differentiation of inactive and active patients (Fig. 5). scopical findings. This is contrary to Florent et alt who Compared with common clinical parameters there found a linear relationship between a,-AT clearance was a good correlation to ESR, serum albumin, and CDAI or serum albumin, but in accordance with orosomucoid and activity index van Hees. Karbach` and Thomas 9 who also failed to prove a The follow up study of four patients with Crohn's on September 26, 2021 by guest. Protected copyright. correlation between intestinal protein loss and extent disease - two with decreasing disease activity (RK, or localisation of inflammation or severity of disease. StCh), one with stable disease (El) and one develop- As with the patients of Karbach our patients with ing intestinal fistulae (MB) - demonstrates that the prior resections had, independent of their actual percentage of faecal excretion of "'In labelled granu- disease activity, a higher a,-AT clearance than locytes run parallel to disease activity in all cases (Fig. patients without surgical treatment in their history 6). Faecal a,-AT, however, showed a parallel trend (Fig. 4). This may be due to copious diarrhoea after only in two patients (RK, El) while it differed extensive previous resections in some patients. We noticeably in the other two patients (StCh, MB) (Fig. therefore found a tendency towards a higher clear- 6). In one patient (StCh) with the lowest a,-AT ance if large bowel segments had been resected. clearance (4 ml/d) resection of an inflamed stenosis Measurement of faecal a,-AT alone was not distinc- lead to an increase of a,-AT clearance up to 164 ml/d tive between resected and unresected patients with despite a fall of disease activity. Similar observations chronic inflammatory bowel diseases (Fig. 4). were reported by Karbach8 who found raised al-AT The percentage of faecal excretion of ..'In labelled clearance in patients after curative resection. granulocytes has been shown to be highly specific for While the percentage of faecal excretion of "'In intestinal inflammation, independent of subjective labelled granulocytes correlated well with serum a,- complaints, extraintestinal manifestations of chronic AT as acute phase reactant there was no correlation inflammatory bowel diseases or other coexisting with a,-AT stool concentration and clearance. Con- diseases.7 Follow up studies in patients with Crohn's sidering these as parameters of intestinal protein loss disease under therapy have shown that the percent- our results indicate that protein loss from the gut does Gut: first published as 10.1136/gut.28.4.386 on 1 April 1987. Downloaded from Faecalalpha-l-antitrypsin in chronic inflammatory bowel diseases 393 not always reflect the actual individual degree of measure of enteric protein loss in children. J Pediair intestinal inflammation. Our own histomorpho- 1981;3:416-8. logical studies seem to confirm this. We found a 7 Saverymuttu SH, Peters AM. Lavender JP, Pepys MB, Hodgson HJF, Chadwick VS. Quantitative fecal significant increase of the percentage excretion with indium-i lI -labeled leukocytes excretion in the assess- the intensity of the granulocyte infiltrate in biopsy ment of disease in Crohn's disease. Gastroenterology specimens, whereas the intestinal protein loss seems 1983; 85: 1333-9. to parallel lymphoplasmocellular infiltrates.' 8 Becker W, Fischbach W, Jennett M, Reiners Chr, Furthermore it has to be questioned again whether Borner W. "'In-oxine-white-blood-cells in diagnosis and faecal excretion and clearance of a,-AT is really an follow-up of Crohn's disease. Klin Wochenschr 1986; 64: accurate correlate of protein loss. Contrary to 141-8. Karbach, Florent and Hill-" Haenay et al" failed to 9 Thomas DW, Sinatra FR, Merritt RJ. Fecal al- confirm a correlation between faecal a,-AT and "Cr- Antitrypsin Excretion in young people with Crohn's disease. J Pediatr Gastroenterol Nutr 1983; 2: 491-6. albumin. On the other hand Saverymuttu et al7 found 10 Beeken WL, Busch HJ, Sylwester DL. Intestinal in a small number of patients a correlation between protein loss in Crohn's disease. Gastroenterology 1972; faecal .'.In leucocyte excretion and faecal 5Cr protein 62: 207-15. excretion. Further investigations are necessary to 11 Malchow H, Ewe K, Brandes W, Goebell H, Ehms H, elucidate these discrepancies. Sommer H, Jeschinsky H. European Cooperative We conclude that the percentage of faecal excre- Crohn's disease study (ECCDS). Results of drug treat- tion of ."In labelled granulocytes is a highly specific ment. Gastroenterology 1984; 86: 249-66. marker of the intestinal inflammation. Changes of 12 Best WR, Becktel JM, Singleton JW, Kern F Jr. individual disease activity are correctly recognised by Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastro- this objective parameter. Faecal excretion and clear- enterology 1976; 70: 439-44. ance of a,-AT are easily available. Assessment of 13 Van Hees PAM, Van Elteren PH, Van Lier HJJ, Van inflammatory activity in an individual patient cannot Tongeren JHM. An index of inflammatory activity be based upon faecal a,-AT stool concentration and in patients with Crohn's disease. Gut 1980; 21: 279- clearance alone. Enteric protein loss does not only 86. depend on the mucosal inflammation but may be 14 Edwards FC, Truelove SC. The course and prognosis of ulcerative Gut 4: 299-315. also influenced by prior resections, complications colitis. 1963; http://gut.bmj.com/ like stenosis, extent and localisation of disease or 15 Becker W, Fischbach W, Reiners Chr, Borner W. "'In- other factors such as bacterial overgrowth, second- oxin markierte Granulozyten bei Morbus Crohn und ary intestinal lymphangiectasia, and unknown Colitis ulzerosa. Fortschr Rontgenstr 1985; 142: 320-5. 16 Andre C, Descos L, Lanais P, Fermanian J. Assessment parameters. of appropriate laboratory measurements to supplement the Crohn's disease activity index. Gut 1981; 22: 571-4. 17 Meryn S, Lochs H, Bettelheim P, Sertl K, Mulak K. References Serumproteinkonzentrationen - Parameter fur die Krankheitsaktivitat bei Morbus Crohn? Leber Magen on September 26, 2021 by guest. Protected copyright. 1 Bernier JJ, Florent CH, Desmazures CH, Aymes CH, Darm 1985; 15: 160-4. L'Hirondel CH. Diagnosis of protein-losing entero- 18 Weeke B, Jarnum S. Serum concentration of 19 serum pathy by gastrointestinal clearance of alpha-i- proteins in Crohn's disease and ulcerative colitis. Gut antitrypsin. Lancet 1978; 2: 763-4. 1971; 12: 297-302. 2 Crossley JR, Elliott RB. Simple method for diagnosing 19 Thomas DW, Sinatra FR, Merritt J. Random fecal al- protein losing enteropathies. Br Med J 1977; 1: 428-9. Antitrypsin concentration in children with gastro- 3 Karbach U, Ewe K, Bodenstein H. Alpha- l-antitrypsin, intestinal disease. Gastroenterology 1981; 80: 776-82. a reliable endogenous marker for intestinal protein loss 20 Meyers S, Wolke A, Field StP, Feuer EJ, Johnson JW, and its application in patients with Crohn's disease. Gut Janowitz HD. Fecal Alpha-l-Antitrypsin Measure- 1983; 24: 718-3. ment: an indicator of Crohn's disease activity. Gastro- 4 Florent C, L'Hirondel C, Desmazures C, Aymes C, enterology 1985; 89: 13-18. Bernier JJ. Intestinal Clearance of a,-Antitrypsin. A 21 Becker W, Fischbach W, Kirchner Th. Leukozytens- sensitive method for the detection of Protein-Losing zintigraphie bei chronisch entzundlichen Darmerkran- enteropathy. Gastroenterology 1981; 81: 777-80. kungen im Vergleich zu Endoskopie, Radiologie und 5 Florent C, L'Hirondel C, Desmazures C, Giraudeaux Histologie. Abstracta XIII. Regensburg, Gesellschaft V, Bernier JJ. Evaluation de l'evolutivite de la maladie fur Gastroenterologie in Bayern, Demeter 1985: de Crohn et de la rectocolite hemorragique par la 31. mesure de la clairance fecale de L'a,-Antitrypsin. 22 Haeney MR, Carter RA, Fields J, Thompson RA, Gastroenterol Clin Biol 1981; 5: 193-7. Asquith P. Is faecal a,-Antitrypsin excretion a reliable 6 Hill RE, Herez A, Corey ML, Gilday DL, Hammilton screening test for protein-losing enteropathy? Lancet JR. Fecal clearance of a,-antitrypsin: A reliable 1979; 2: 1161-2.