faeces in response to secretin and cholecystokininpancreozymin

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Gut, 1974, 15, 132-138 Trypsin nd chymotrypsin in duodenl spirte nd feces in response to secretin nd cholecystokininpncreoymin J K SALE, D M GOLDBERG, B THJODLEIFSSON, AND K G WORMSLEY' From the

1 Gut, 1974, 15, Trypsin nd chymotrypsin in duodenl spirte nd feces in response to secretin nd cholecystokininpncreoymin J K SALE, D M GOLDBERG, B THJODLEIFSSON, AND K G WORMSLEY' From the Deprtment of Chemicl Pthology, Royl Hospitl, Sheffield, nd The Deprtment of Therpeutics, University of Dundee SUMMARY The secretion of trypsin nd chymotrypsin into the duodenum in response to secretin nd CCK-PZ hs been compred with the fecl excretion of the enymes following similr stimultion in 47 individuls undergoing clinicl investigtion The fecl output of chymotrypsin correlted well, but trypsin less stisfctorily, with the secretion of the respective enymes into the duodenum The fecl excretion of chymotrypsin following stimultion with secretin nd CCK-PZ cn therefore be used s n index of pncretic enyme-secretory cpcity The secretion of bicrbonte into the duodenum in response to secretin is stisfctory nd widely used criterion for ssessing the secretory cpcity of the exocrine pncres (Wormsley, 1972) despite the ssumed origin of the bicrbonte from the biliry system nd duodenl mucos s well s the pncres Recently, the vilbility of cholecystokinin-pncreoymin (CCK-PZ) nd derivtives or nlogues hs resulted in ttempts to utilie the specific pncretic secretion of enymes into the duodenum to mesure pncretic exocrine function (Burton, Evns, Hrper, Howt, Oleesky, Scott, nd Vrley, 196; Sun, 1963; Bnwell, Northm, nd Cooke, 1967; Wormsley, 1969; Ribet, Duffut, Vysse, nd Lvl, 1972) However, for resons rnging from psychologicl to ntomicl, it is impossible to intubte the duodenum to obtin spirte for nlysis in some dults nd children in whom investigtion of pncretic exocrine function is cliniclly necessry The present study hs tested the fesibility of mesuring pncretic enyme-secretory cpcity, while voiding the necessity for intubtion, by compring the mounts of trypsin nd chymotrypsin excreted in the feces with the mounts secreted into the duodenum following stimultion with secretin nd CCK-PZ 'Address communictions to KGW, Ninewells Hospitl, Dundee DD2 lub Received for notifiction 28th November 1973 Methods All 47 subjects required ssessment of pncretic exocrine function during the clinicl investigtion of symptoms, or combintions of symptoms, such s bdominl pin, dibetes mellitus, or stetorrhoe (see tble) Ech individul underwent two tests, comprising intubtion nd fecl enyme collection, in rndom order, with n intervl of t lest three dys between tests Informed consent ws obtined for ech procedure Techniques of gstric nd duodenl intubtion nd hormonl stimultion hve been described previously (Wormsley, 1969; Goldberg, Sle, Fwcett, nd Wormsley, 1972) Ech subject received n intrven- Dignosis No of Cses Confirmtion of Dignosis Duodenl ulcer 11 Lprotomy Postcute pncretitis 7 Lprotomy Gstric ulcer 7 Lprotomy Norml (dhesions, 6 Lprotomy or endoscopy Mllory-Weiss) Dibetes mellitus 2 Biochemicl evidence Pncretic crcinom 2 Lprotomy Chronic pncretitis 2 Lprotomy Crohn's disese 2 Rdiology Coelic disese 2 Biopsy Motor neurone disese 2 Electromyogrphy etc Peripherl neuritis 1 Electromyogrphy etc Gllstones 1 Lprotomy Cushing's syndrome 1 Lprotomy Immunoglobulin deficiency 1 Biochemicl evidence Tble 132 Finl dignostic sttus of 47 ptients

Trypsin nd chymotrypsin in duodenl spirte ndfeces in response to secretin nd CCK-PZ ous infusion of 15 M sodium chloride contining secretin in dose of 1 clinicl unit per kg body weight ech hour plus

2 Trypsin nd chymotrypsin in duodenl spirte ndfeces in response to secretin nd CCK-PZ ous infusion of 15 M sodium chloride contining secretin in dose of 1 clinicl unit per kg body weight ech hour plus CCK-PZ in dose of 1 Ivy unit per kg ech hour, for 5 minutes The totl 5-minute outputs of trypsin nd chymotrypsin were clculted for ech subject nd re referred to in the text s 'outputs (of the respective enymes) in duodenl spirte' The hormones were obtined from the GIH Lbortory, Krolinsk Institute, Stockholm On the evening before the fecl enyme test, ech subject ws given glycerol suppository (BP) (4 g) t 2 hours The tretment ws repeted next morning t 7 hours, in order to evcute colonic fecl residues At 8 hours, ech individul received 3 ml of mixture contining 5 g sodium bicrbonte nd 3 ml of mist mgnesium sulphte (BP) The sme infusion of hormones ws then given s during duodenl intubtion After the infusion, ech individul received further 3 ml of ech of the sodium bicrbonte nd mgnesium sulphte mixtures, together with cpsule contining 3 crmine (to ct s fecl mrker) Brekfst ws deferred until 93 hours nd the remining mels were tken t the norml times Feces were pssed directly into weighed 3 1 polythene bekers, stnding in bowl filled with ice The feces were collected in two btches-from 8 to 14 hours nd from 14 to 8 hours, respectively The bekers contining feces were weighed wi C) J rf=56 x-j47y +48, l C T on completion of the pproprite collection period nd the contents were homogenied Mesured mounts of 15 M sodium chloride were dded, s necessry Aliquots were obtined from ech homogenied smple nd stored t - 2 C before nlysis The ctivities of trypsin nd chymotrypsin were mesured s described previously, using p-tosylrginine methyl ester nd cetyl tyrosine ethyl ester s respective substrtes (Goldberg et l, 1972; Goldberg nd Wormsley, 197) One mle ptient with totl pncretic chyli (shown by lprotomy nd biopsy to be due to ftty replcement of the pncretic cinr tissue) underwent further test A polythene tube (1 mm d) ws pssed so tht the tip ly in the jejunum, just beyond the duodeno-jejunl junction Three-hundred purified trypsin (Sigm Chemicl Co Ltd; ct no T8253) plus 1 crmine were infused into the jejunum nd followed by mgnesium sulphte in order to promote purgtion The feces were collected s bove Results EFFECT OF PURGATIVE AND OF CARMINE ON ENZYMIC ACTIVITIES Neither the mgnesium sulphte nor the crmine ffected the ctivities of trypsin nd chymotrypsin in the doses used in the present study Og ic - EU" : E U 4 A A 2 3 9, JU HOUR FAECES 24 HOUR FAECES Fig 1 Comprison of outputs of chymotrypsin in duodenl spirte ndfeces Ech point represents the outputs of chymotrypsin ofone individul in duodenl spirte compred with the fecl outputs in the six-hour nd 24-hour collections fter stimultion with secretin nd CCK-PZ The two points t the origin denote two subjects with no detectble output of enymes r = -611 x = 36 y +'42 133

134 W U 49 41 2 - - r =477 x-41 y + 133 J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley -U U : Lx1=31y +14 2 4 16 36 56 6 HOUR FAECES 24 HOUR FAECES Fig 2 Comprison of outputs of trypsin in

3 134 W U r =477 x-41 y J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley -U U : Lx1=31y HOUR FAECES 24 HOUR FAECES Fig 2 Comprison of outputs of trypsin in duodenl spirte ndfeces Significnce of symbols s in figure 1 RECOVERY OF CARMINE Crmine ppered in the fecl contents within six hours of dministrtion in 8% of subjects nd in ll individuls during the second collection period RELATIONSHIP OF CHYMOTRYPSIN OUTPUTS IN DUODENAL ASPIRATE AND FAECES There ws significnt correltion (fig 1) between the outputs of chymotrypsin in duodenl spirte nd feces In 53% of subjects, the fecl content of chymotrypsin during the first six-hour collection period ws greter thn the output in the duodenl spirte nd the proportion incresed to 74% with the totl 24-hour collection The 24-hour fecl content of chymotrypsin ws less thn hlf the vlue of duodenl spirte in only three individuls (one ptient ech with pncretic crcinom nd Crohn's disese nd one ptient recovering from cute pncretitis) RELATIONSHIP OF TRYPSIN OUTPUTS IN DUODENAL ASPIRATE AND FAECES The reltionship between duodenl nd fecl outputs of trypsin ws not s good s for chymotrypsin (fig 2) In the mjority of individuls, the fecl content of trypsin ws less in the feces thn in duodenlspirte, both in the six-hour (81 % of ptients) nd in the 24-hour collections (72 % of ptients) RELATIONSHIP OF SUM OF CHYMOTRYPSIN PLUS TRYPSIN IN DUODENAL ASPIRATE AND FAECES The correltion between duodenl nd fecl outputs of the sum of both proteses ws s good (fig 3) s the correltion between the duodenl nd fecl outputs of chymotrypsin lone QUANTITATIVE CHANGE IN ACTIVITY OF TRYPSIN AND CHYMOTRYPSIN DURING INTESTINAL TRANSIT Assuming tht trypsin nd chymotrypsin were secreted in the sme rtio in response to mgnesium sulphte nd to food s into the duodenum in response to the exogenous hormones, it ws clculted from the fecl outputs of chymotrypsin tht the fecl excretion of trypsin during 24 hours represented losses during intestinl trnsit mounting to s much s four times the output of trypsin secreted in response to the 5-minute period of stimultion with secretin nd CCK-PZ (fig 4) RATIO OF CHYMOTRYPSIN TO TRYPSIN IN DUODENAL ASPIRATE AND FAECES The rtio of chymotrypsin to trypsin incresed in ll except six subjects during trnsit through the intestine (fig 5) The two most significnt decreses in rtio occurred in one ptient with Cushing's syndrome nd in one with pncretic crcinom, in whom the rtios hd been unusully high in the duodenl spirte (compred with the norml rnge, s described previously by Goldberg, Sle, nd Wormsley, 1973) FATE OF TRYPSIN INFUSED INTO THE JEJUNUM Fecl output of trypsin during the 24 hours fter

4 Trypsin nd chymotrypsin in duodenl spirte nd feces in response to secretin nd CCK-PZ 135 W m -_ W Fig 3 S- C- ct 4- WI- : U Fig 4 6C 2 I IJP 8-4- I- S 4L2 6 6 HOUR FAECES Trypsin Per Cent Duoden CT & T r = 66 lx= 39y ^ ^ ^ HOUR FAECES Fig 3 Comprison of sums of outputs of chymotrypsin plus trypsin in duodenl spirte nd feces Significnce of symbols s in figure r = 574 x= O-Sly S S S@@ d Fig 4 Clculted estimtes of chnge in tryptic ctivity during intestinl trnsit Ech point represents the result from one individul, clculted from the 24-hour fecl outputs of trypsin nd chymotrypsin s described in the text The vlues represented by the ordinte refer to chnges in tryptic ctivity depicted both in bsolute terms () or s proportion (percentge duodenl) of the output of trypsin into the duodenum in response to stimultion with secretin nd CCK-PZ The minus sign indictes clculted loss of tryptic ctivity; the plus sign indictes clculted gin

136 g cn C,,S I- - 5-4- 3-2- 1-5- 3-2- 1- - Duodenl Aspirte J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley r 24 Hour Feces Fig 5 Rtio of chymotrypsin to trypsin in duodenl spirte nd 24-hour

5 136 g cn C,,S I Duodenl Aspirte J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley r 24 Hour Feces Fig 5 Rtio of chymotrypsin to trypsin in duodenl spirte nd 24-hour fecl collection Ech pir ofpoints represents results from one or more individuls The scle is not continuous nd is interrupted, s shown, s the rtio increses to greter thn 3 dministrtion mounted to 23% of the mount infused into the jejunum of the ptient with pncretic chyli Discussion The present study is the first to compre the hormonlly stimulted secretion of the pncretic enymes trypsin nd chymotrypsin into the duodenum with the fecl excretion of the enymes fter similr hormonl stimultion The report describes the methodology nd vlidtion of the comprison STIMULANT SCHEDULES The dosge of stimulnt hormones ws selected both to ccord with the specified stimulnt schedule of current interntionl multicentre study of tests of pncretic exocrine function nd lso in order to provide the highest rte of secretion into the duodenum together with the gretest degree of inhibition of gstric cid secretion comptible with stisfctory stimultion of pncretic enymes Inhibition of gstric cid secretion, which results from the infusion of the combined hormones (Henriksen nd J6rgensen, 1973), ws sought becuse pncretic proteses re rpidly nd irreversibly inctivted by pepsin in the presence of cid (Heier, Clevelnd, nd Iber, 1965; Goldberg, Cmpbell, nd Roy, 1969) nd it therefore seemed desirble to suppress gstric cid secretion s much s possible, prticulrly becuse it hd been shown tht duodeno-gstric reflux sometimes occurred during pncretic stimultion with exogenous hormones (Wormsley, 1972b) In order to minimie further destruction of pncretic enymes by gstric juice pssing into the duodenum nd to void destruction of enymes regurgitted into the stomch, sodium bicrbonte ws given before nd fter the period of pncretic stimultion ADMINISTRATION OF MAGNESIUM SULPHATE Pncretic enymes re inctivted during intestinl trnsit, lthough the mechnisms re not known (Wormsley nd Goldberg, 1972) The degree of inctivtion ppers to be lessened if the rte of intestinl trnsit is incresed (Ammnn, 1967) It therefore seemed pproprite to induce dirrhoe with sline purgtive (Mrtindle, 1972) in order to minimie inctivtion of the exogenously stimulted pncretic enymes during pssge through the intestine Mgnesium sulphte in the duodenum lso elicits secretion of pncretic juice rich in enymes (Hirschberg, 1928) nd dischrge of bile (Boyden, Bergh, nd Lyne, 1943) which my, in turn, stimulte the pncretic secretion of enymes (Forell nd Sthlheber, 1966; Wormsley, 197; Forell, Otte, Kohl, Lehnert, nd Sthlheber, 1971) on contct with the duodenl mucos The use of mgnesium sulphte my therefore prolong nd increse the stimulus provided by the exogenous hormones to the pncretic secretion of enymes INTERRELATIONSHIP OF THE ENZYMES The present study hs confirmed the reversl of the rtio of trypsin to chymotrypsin during intestinl

Trypsin nd chymotrypsin in duodenl spirte nd feces in response to secretin nd CCK-PZ trnsit nd the significntly greter recovery of chymotrypsin thn trypsin in the feces, which hs been described

6 Trypsin nd chymotrypsin in duodenl spirte nd feces in response to secretin nd CCK-PZ trnsit nd the significntly greter recovery of chymotrypsin thn trypsin in the feces, which hs been described previously (Hverbck, Dyce, Gutentg, nd Montgomery, 1963; Dyck nd Ammnn, 1965; Ammnn, Tgwercher, Kshiwgi, nd Rosenmund, 1968) The reson for the persistently high fecl content of trypsin in few individuls is not cler, but high fecl outputs tend to occur in subjects who hve high rtes of secretion of trypsin into the duodenum Two hypotheses were considered in n ttempt to explin the reltively greter reduction of tryptic thn chymotryptic ctivity during intestinl trnsit The less probble hypothesis-tht both types of pncretic protese were eqully inctivted but tht chymotryptic ctivity ws derived from sources other thn pncres during pssge through the intestine-ws disproved, since the ptient with pncretic chyli did not excrete chymotrypsin It seems likely, therefore, tht the disppernce of tryptic ctivity is due to greter degree of inctivtion of trypsin thn chymotrypsin during intestinl trnsit Nothing is known bout the extent of inctivtion of the humn pncretic proteses during intestinl trnsit, so tht the bsolute rtes of degrdtion of trypsin nd chymotrypsin cnnot be ccurtely evluted However, n ttempt hs been mde in the present report to clculte the pproximte loss of tryptic ctivity during intestinl trnsit, bsed on the propositions tht the two proteses hve been secreted throughout the dy in the sme proportion s in hormonlly stimulted duodenl spirte nd tht chymotrypsin is not significntly degrded during intestinl trnsit On the bsis of these ssumptions, it hs been shown tht the medin dily loss of tryptic ctivity is equivlent to 15 of trypsin The estimte must, however, be interpreted with due regrd to two probble sources of error inherent in the underlying ssumptions In the first plce, it is likely tht some inctivtion of chymotrypsin occurs, so tht the clculted loss of trypsin is too low by fctor which depends on the degree of loss of chymotryptic ctivity during intestinl trnsit No bsolute vlues for loss of chymotryptic ctivity during pssge through the intestine re vilble but comprison of the high verge vlues for dily outputs of chymotrypsin in ileostomy effluent (Goldberg et l, 1972) with the fecl outputs of chymotrypsin in the present study indictes tht some inctivtion of chymotrypsin probbly tkes plce in the colon Secondly, evidence from two studies (Borgstrbm, Dhlqvist, Lundh, nd Sjovll, 1957; Worning nd Mullert, 1966) indictes tht the concentrtion of chymotrypsin my be greter thn trypsin in the duodenl contents fter (Lundh) mel If the rtio of chymotrypsin to trypsin in the pncretic juice secreted in response to food is greter thn in response to exogenous hormones, the clculted loss of trypsin during intestinl trnsit hs been overestimted by fctor depending on the reltive contribution of the food-stimulted secretion of proteses to the totl output of the proteses in the feces CORRELATION OF DUODENAL AND FAECAL ENZYME-SECRETORY RATES Following stimultion with secretin plus CCK-PZ there is very good correltion between thesecretion of chymotrypsin into the duodenum during the 5- minute test period nd the output of chymotrypsin in the feces during the subsequent 24 hours, despite the fct tht the 24-hour fecl collection contins not only the chymotrypsin secreted in response to the hormones, but lso vrible proportions of the pncretic enyme response to three mels nd to the purgtive Fecl output of chymotrypsin less thn hlf the duodenl output ws found in only three subjects, so tht the fecl content of chymotrypsin gve n excellent indiction of the order of mgnitude of the pncretic enyme-secretory cpcity for chymotrypsin, s represented by the response to exogenous hormones Correltion between the duodenl nd fecl outputs of chymotrypsin during the first six hours fter stimultion ws not s good s for the 24-hour collection, indicting tht the intestinl trnsit of the hormonlly stimulted pncretic enymes, like crmine, ws probbly incomplete during the shorter collection period The fecl excretion of trypsin less ccurtely reflected the mount secreted into the duodenum in response to exogenous hormones When fecl content of trypsin ws high, the pncretic cpcity to secrete trypsin ws lso high, but the converse ws not necessrily true, since very low levels of tryptic ctivity in the feces were found in subjects whose cpcity to secrete trypsin ws quite norml The fecl content of trypsin lone cnnot therefore be used s relible index of pncretic enymesecretory cpcity lthough the combined outputs of chymotrypsin nd trypsin correlted well with the combined outputs of the two proteses into the duodenum Mesurement of the concentrtions of chymotrypsin nd, to lesser extent, trypsin in rndom smples of feces hs been employed s screening test for the detection of pncretic disese for 1 yers (Hverbck et l, 1963; Dyck nd Ammnn, 1965; Ammnn et l, 1968; Muller, Wisniewski, nd Hnsky, 197) but the vlidity of using the concentrtion of pncretic enymes in 'spot' stool smples s n index of pncretic function hs been ques-

138 J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley tioned (Bnwell, Leonrd, nd Lobo, 1965; Wilding, Bnwell, nd Cooke, 1966; Smith, Ediss, Mullinger, nd Bogoch, 1971) In the present study n

7 138 J K Sle, D M Goldberg, B Thjodleifsson, nd K G Wormsley tioned (Bnwell, Leonrd, nd Lobo, 1965; Wilding, Bnwell, nd Cooke, 1966; Smith, Ediss, Mullinger, nd Bogoch, 1971) In the present study n ttempt hs been mde to improve the correltion between pncretic enyme-secretory sttus nd fecl excretion of the pncretic enymes by ensuring more strictly controlled stimultion of pncretic enyme secretion nd quntittive determintion of the resulting output of the pncretic enymes in the stool before ssessing the use of the technique in confirming the clinicl dignosis nd estblishing the success of therpy in pncretic disorders The results of the present study indicte tht the fecl excretion of chymotrypsin following stimultion with secretin nd CCK-PZ cn be used s n index of pncretic enyme-secretory cpcity During the course of the study, KGW hs received consecutive reserch grnts from the Cystic Fibrosis Reserch Trust nd the Scottish Hospitl Endowments Reserch Trust, which re grtefully cknowledged DMG ws generously supported by the Endowment Fund of the United Sheffield Hospitls References Ammnn, R W (1967) Fortschritte in der Pnkresfunktionsdignostik P 27-3 Springer, Berlin Ammnn, R W, Tgwercher, E, Kshiwgi, H, nd Rosenmund, H (1968) Dignostic vlue of fecl chymotrypsin nd trypsin ssessment for detection of pncretic disese Amer J dig Dis, 13, Bnwell, J G, Leonrd, P J, nd Lobo, R M F (1965) Mesurement of trypsin nd chymotrypsin ctivity in stools to detect chronic pncretic disese Gut, 6, Bnwell, J G, Northm, B E, nd Cooke, W T (1967) Secretory response of the humn pncres to continuous intrvenous infusion of pncreoymin-cholecystokinin (Cecekin) Gut, 8, Borgstrom, B, Dhlqvist, A, Lundh, G, nd Sjovll, J (1957) Studies of intestinl digestion nd bsorption in the humn J clin Invest, 36, Boyden, E A, Bergh, G S, nd Lyne, J A (1943) An nlysis of the rection of the humn gll bldder nd sphincter of Oddi to mgnesium sulphte Surgery, 13, Burton, P, Evns, D G, Hrper, A A, Howt, H T, Oleesky, S, Scott, J E, nd Vrley, H (196) A test of pncretic function in mn bsed on the nlysis of duodenl contents fter dministrtion of secretin nd pncreoymin Gut, 1, Dyck, W, nd Ammnn, R (1965) Quntittive determintion of fecl chymotrypsin s screening test for pncretic exocrine insufficiency Amer J dig Dis, 1, Forell, M M, Otte, M, Kohl, H J, Lehnert, P, nd Sthlheber, H P (1971) The influence of bile nd pure bile slts on pncretic secretion in mn Scnd J Gstroent, 6, Forell, M M, nd Sthlheber, H P (1966) Gllefluss nd Pnkressekretion Klin Wschr, 44, Goldberg, D M, Cmpbell, R, nd Roy, A D (1969) Fte of trypsin nd chymotrypsin in the humn smll intestine Gut, 1, Goldberg, D M, Cmpbell, R, nd Roy, A D (1972) An investigtion of the role of intrluminl proteolytic enymes nd intrcellulr enyme inhibitors in ulcertive colitis Brit J exp Pth, 53, Goldberg, D M, Sle, J K, Fwcett, A N, nd Wormsley, K G (1972) Trypsin nd chymotrypsin s ids in the dignosis of pncretic disese Amer J dig Dis, 17, Goldberg, D M, Sle, J K, nd Wormsley, K G (1973) Rtio of chymotrypsin to trypsin in humn duodenl spirte Digestion, 8, Goldberg, D M, nd Wormsley, K G (197) The interreltionships of pncretic enymes in humn duodenl spirte Gut, 11, Hverbck, B J, Dyce, B J, Gutentg, P J, nd Montgomery, D W (1963) Mesurement of trypsin nd chymotrypsin in stool: dignstic test for pncretic exocrine insufficiency Gstroenterology, 44, Heier, W D, Clevelnd, C R, nd Iber, F L (1965) Gstric inctivtion of pncretic supplements Johns Hopk med J, 116, Henriksen, F W, nd Jorgensen, S P (1973) Inhibition of gstric secretion by secretin nd cholecystokinin (Abstr) Act endocr (Kbh), Suppl 177, 332 H-irschberg, L (1928) Sekretorische Funktion der Leber, des Pnkres und des Mgens nch Einfuhrung von MgSO, ins Duodenum Arch Verduungskr, 44, Mrtindl, W (1972) The Extr Phrmcopoei, p , edited by N W Blcow, 26th ed Phrmceuticl Press, London Muller, L, Wisniewski, Z S, nd Hnsky, J (197) The mesurement of fecl chymotrypsin: screening test for pncretic exocrine insufficiency Aust Ann Med, 19, Ribet, A, Diff it, M, Vysse, N, nd Lvl, J (1972) Interet de l cerul6ine en perfusion dns ]'explortion fonctionelle du pncr6s exocrine Arch Ml Appr dig, 61, Smith, J S, Ediss, I, Mullinger, M A, nd Bogoch, A (1971) Fecl chymotrypsin nd trypsin determintions Cnd med Ass J, 14, Sun, D C H (1963) Norml vlues for the pncreoymin-secretin test Gstroenterology, 44, Wilding, P, Bnwell, J G, nd Cooke, W T (1966) Fecl enyme ssy s n id to the dignosis of pncretic exocrine insufficiency Am?r J dig Dis, 11, Wormsley, K G (1969) The response to infusion of combintion of secretin nd pncreoymin in helth nd disese Scnd J Gstrosnt, 4, Wormsley, K G (197) Stimultion of pncretic secretion by intrduodenl infusion of bile slts Lncet, 2, Wormsly, K G (1972) Pncretic function tests Clin Gstroent 1, Wormsley, K G (1972b) Aspects of duodeno-gstric reflux in mn Gut, 13, Wormsley, K G, nd Goldberg, D M (1972) The interreltionships of the pncretic enymes Gut, 13, Worning, H, nd Mullert, S (1966) ph nd pncretic enymes in the humn duodenum during digestion of stndrd mel Scnd J Gstroent, 1,

in human duodenal aspirate'

in human duodenal aspirate' Gut, 197, 11, 859-866 The interreltionships of pncretic enymes in humn duodenl spirte' D M GOLDBERG ND K G WORMSLEY From the Royl Hospitl nd Royl Infirmry, Sheffield SMMRY The interreltionships of proteolytic