5
Gut, Editorial Committee SHEILA SHERLOCK (Editor) NORMAN C. TANNER (Assistant Editor) C. C. BOOTH I. A. D. BOUCHIER WILFRID CARD B. CREAMER RICHARD DOLL R. H. DOWLING H. L. DUTHIE R. A. GREGORY 0. H. A. HUBSCHER ANDREW W. KAY F. H. KEMP J. LAWS J. E. LENNARD-JONES B. C. MORSON A. E. A. READ E. N. ROWLANDS R. SHIELDS W. P. SMALL GEOFFREY WATKINSON R. B. WELBOURN A. W. WOODRUFF E D I TO R British Medical Journal The object of Gut is to publish original papers and reviews concerned with practice and research in the field of gastroenterology. The field is that ofalimentary, hepatic, or pancreatic disease, and papers may cover the medical, surgical, radiological, or historical aspects. They may also deal with the basic sciences concerned with the alimentary tract, including experimental work. The report of a single case will be accepted only if it is of sufficient interest in relation to a wider field of research. There will be a section devoted to short papers on laboratory and surgical techniques and methods of investigation where these are not part of a lesser survey. COMMuNICATIONS Papers should be addressed to the Editor, Gut, B.M.A. House, Tavistock Square, London, WC1H 9JR. Papers are accepted only on the understanding that they are not published elsewhere without previous sanction of the Editorial Board. They should be in double-spaced typewriting on one side of the paper only. On the paper the name of the author should appear with initials (or distinguishing Christian name) only, and the name and address of the hospital or laboratory where the work was performed. A definition of the position held by each of the authors in the hospital or laboratory should be stated in a covering letter to the Editor. Communications should be kept short, and illustrations should be included when necessary; coloured illustrations are allowed only if monochrome will not satisfactorily demonstrate the condition. It is not desirable that results should be shown both as tables and graphs. ILLUSTRATIONS Diagrams should be drawn in indian ink on white paper, Bristol board, or blue-squared paper. The legends for illustrations should be typed on a separate sheet and numbered to conform with the relevant illustrations. Photographs and photomicro- graphs should be on glossy paper, unmounted. TABLES should not be included in the body of the text, but should be typed on a separate sheet. ABBREVIATIONS In general, symbols and abbreviations should be those used by British Chemical and Physio- logical Abstracts. In any paper concerning electrolyte metabolism, it is desirable that data be calculated as m-equiv/l. as well as (or alternatively to) mg/100 ml. REFERENCES These should be made by inserting the name of the author followed by year of publication in brackets. At the end of the paper, references should be arranged in alphabetical order of authors' names. Such references should give author's name, followed by initials and year of publication in brackets, the title of the article quoted, the name of the journal in which the article appeared, the volume number in arabic numerals, followed by the numbers of first and last pages of the article. Abbreviations are according to World Medical Periodicals (published by B.M.A. for World Medical Association), thus: Chandler, G. N., Cameron, A. D., Nunn, A. H., and Street, D. F. (1960). Early investigations of haematemesis. Gut, 1, 6-13. REPRINTS Fifty reprints will be supplied free of charge. Further reprints will be available on payment of the necessary costs; an indication of the number of reprints required should be sent to the Publishing Manager on the form provided with the proofs. NOTICE TO ADVERTISERS Application for advertise- ment space and for rates should be addressed to the Advertisement Manager, Gut, B.M.A. House, Tavis- tock Square, London, WC1IH 9JR. NOTICE TO SUBSCRIBERS Gut is published monthly. The annual subscription rate is £8 8s. in the United Kingdom and the Republic of Ireland, and £9 Ss. [$22.00 U.S.A.1 in all countries overseas. Payment for overseas subscriptions should be made in sterling, i.e., £9 Ss., and sent by Mail Transfer-Charges Remitter-through a Bank to the British Medical Association. Orders can also be placed locally with any leading subscription agent or bookseller. (For the convenience of readers in the U.S.A. subscription orders, with or without payment, can also be sent to: British MedicalJournal, 1172 Commonwealth Avenue, Boston, Mass. 02134. All inquiries, however, must be addressed to the Publisher in London.) Copies of single issues of the Journal are available at the following prices, including postage and packing: Inland: £1. Abroad: £1 Ss. U.S.A.: $3.00. COPYRIGHT ( 1970 by Gut. All rights of reproduction are reserved in respect of all papers, articles, tables, illustrations, etc., published in this Journal in all countries of the world.

Editorial Committee · gut, editorial committee sheila sherlock(editor) norman c. tanner(assistant editor) c. c. booth i. a. d. bouchier wilfrid card b. creamer richard doll r. h

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Page 1: Editorial Committee · gut, editorial committee sheila sherlock(editor) norman c. tanner(assistant editor) c. c. booth i. a. d. bouchier wilfrid card b. creamer richard doll r. h

Gut, Editorial CommitteeSHEILA SHERLOCK (Editor)NORMAN C. TANNER (Assistant Editor)

C. C. BOOTHI. A. D. BOUCHIERWILFRID CARDB. CREAMERRICHARD DOLLR. H. DOWLINGH. L. DUTHIER. A. GREGORY0. H. A. HUBSCHERANDREW W. KAYF. H. KEMPJ. LAWS

J. E. LENNARD-JONESB. C. MORSONA. E. A. READE. N. ROWLANDSR. SHIELDSW. P. SMALLGEOFFREY WATKINSONR. B. WELBOURNA. W. WOODRUFFED ITOR British Medical Journal

The object of Gut is to publish original papers andreviews concerned with practice and research in thefield ofgastroenterology. The field is that ofalimentary,hepatic, or pancreatic disease, and papers may coverthe medical, surgical, radiological, or historical aspects.They may also deal with the basic sciences concernedwith the alimentary tract, including experimental work.The report of a single case will be accepted only if it isof sufficient interest in relation to a wider field ofresearch.There will be a section devoted to short papers on

laboratory and surgical techniques and methods ofinvestigation where these are not part of a lessersurvey.COMMuNICATIONS Papers should be addressed to theEditor, Gut, B.M.A. House, Tavistock Square,London, WC1H 9JR. Papers are accepted only on theunderstanding that they are not published elsewherewithout previous sanction of the Editorial Board.They should be in double-spaced typewriting on oneside of the paper only. On the paper the name of theauthor should appear with initials (or distinguishingChristian name) only, and the name and address of thehospital or laboratory where the work was performed.A definition of the position held by each of the authorsin the hospital or laboratory should be stated in acovering letter to the Editor. Communications shouldbe kept short, and illustrations should be includedwhen necessary; coloured illustrations are allowedonly ifmonochrome will not satisfactorily demonstratethe condition. It is not desirable that results shouldbe shown both as tables and graphs.ILLUSTRATIONS Diagrams should be drawn in indianink on white paper, Bristol board, or blue-squaredpaper. The legends for illustrations should be typed ona separate sheet and numbered to conform with therelevant illustrations. Photographs and photomicro-graphs should be on glossy paper, unmounted.TABLES should not be included in the body of the text,but should be typed on a separate sheet.ABBREVIATIONS In general, symbols and abbreviationsshould be those used by British Chemical and Physio-logical Abstracts. In any paper concerning electrolytemetabolism, it is desirable that data be calculated asm-equiv/l. as well as (or alternatively to) mg/100 ml.

REFERENCES These should be made by inserting thename of the author followed by year of publication inbrackets. At the end of the paper, references should bearranged in alphabetical order ofauthors' names. Suchreferences should give author's name, followed byinitials and year of publication in brackets, the title ofthe article quoted, the name of the journal in which thearticle appeared, the volume number in arabicnumerals, followed by the numbers of first and lastpages of the article. Abbreviations are according toWorld Medical Periodicals (published by B.M.A. forWorld Medical Association), thus: Chandler, G. N.,Cameron, A. D., Nunn, A. H., and Street, D. F. (1960).Early investigations of haematemesis. Gut, 1, 6-13.REPRINTS Fifty reprints will be supplied free ofcharge.Further reprints will be available on payment of thenecessary costs; an indication of the number ofreprints required should be sent to the PublishingManager on the form provided with the proofs.NOTICE TO ADVERTISERS Application for advertise-ment space and for rates should be addressed to theAdvertisement Manager, Gut, B.M.A. House, Tavis-tock Square, London, WC1IH 9JR.NOTICE TO SUBSCRIBERS Gut is published monthly.The annual subscription rate is £8 8s. in the UnitedKingdom and the Republic of Ireland, and £9 Ss.[$22.00 U.S.A.1 in all countries overseas. Paymentfor overseas subscriptions should be made in sterling,i.e., £9 Ss., and sent by Mail Transfer-ChargesRemitter-through a Bank to the British MedicalAssociation. Orders can also be placed locally withany leading subscription agent or bookseller. (For theconvenience of readers in the U.S.A. subscriptionorders, with or without payment, can also be sent to:British MedicalJournal, 1172 Commonwealth Avenue,Boston, Mass. 02134. All inquiries, however, must beaddressed to the Publisher in London.) Copies ofsingle issues of the Journal are available at thefollowing prices, including postage and packing:Inland: £1. Abroad: £1 Ss. U.S.A.: $3.00.COPYRIGHT ( 1970 by Gut. All rights of reproductionare reserved in respect of all papers, articles, tables,illustrations, etc., published in this Journal in allcountries of the world.

Page 2: Editorial Committee · gut, editorial committee sheila sherlock(editor) norman c. tanner(assistant editor) c. c. booth i. a. d. bouchier wilfrid card b. creamer richard doll r. h

533 Technique

of the distal portion of the duodenum is closed andthe proximal duodenum is anastomosed end to side tothe intestine in the region of the duodeno-jejunaljunction. It was considered that this arrangementwould be preferable to anastomosing the duodenumin continuity since the cannula traverses the lumenof the duodenum and might obstruct it (Fig. 3).A hole is made in the antimesenteric border of the

duodenal pouch and one end of cannula A insertedand secured with a purse string suture around thestem of the cannula. The wall of the pouch is alsosutured to the large flange. The other end of thecannula is inserted through a hole in the side of theclosed duodenal stump and similarly secured. The endof cannula B is then passed through a hole in theopposite wall of the duodenal stump and it is screwedfirmly into cannula A. A purse string suture securesthe duodenal wall around the cannula and othersutures secure it to the wide flange. The stem of thecannula is then brought out through the abdominalwall at a suitable site. A third cannula is inserted intothe stomach and brought out through the abdominalwall to the left of the midline. The abdomen is thenclosed in layers.

Experience with the Cannula

Two dogs have been prepared with this type ofcannula. Both dogs had an uneventful postoperativecourse and were in excellent health four months later.The cannula system has remained watertight to pres-sures up to 80 cm saline. Each has been the subjectof 16 experiments. In a series of tests in which thedogs were given constant-rate infusions of secretinover short periods of time (quarter to one hour) theflow rates were found to rise with increasing dosageand the dose response curves show close agreementbetween flow rates in separate tests at any givendosage.

I wish to thank Mr F. D. Naylor for his invaluablehelp in preparing the experimental animals and in theexperiments themselves, Professor H. L. Duthie andDr K. G. Wormsley for their advice and encourage-ment, and Mrs A. Bemey for secretarial assistance.

Reference

Stening, G. F. (1969). A modification of a chronic pancreaticfistula in the dog. Brit. J. Surg., 56, 308-310.

The May 1970 IssueTHE MAY 1970 ISSUE CONTAINS THE FOLLOWING PAPERS

Studies on intestinal absorption of amino acidsand a dipeptide in a case of Hartnup diseaseF. NAVAB AND A. M. ASATOOR

Intestinal absorption of two dipeptides inHartnup diseaseA. M. ASATOOR, B. CHENG, K. D. G. EDWARDS, A. F.LANT, D. M. MATTHEWS, M. D. MILNE, F. NAVAB,AND A. J. RICHARDS

The neurological lesion in achalasia of the cardiaBARBARA SMITH

The effects on human gastric secretion of pro-longed continuous intravenous infusions ofmaximal and supramaximal doses of histamineacid phosphate and pentagastrinD. A. AUBREY

Effects of histamine acid phosphate and penta-gastrin on gastric secretion in normal humansubjects D. A. AUBREY AND A. P. M. FORREST

Recurrent ulcer after vagatomy and pyloroplasty:the x-ray appearances and their value in diagnosisJ. ALEXANDER WILLIAMS AND D. S. M. TOYE

Experiences with a rat bio-assay in the diagnosis ofthe Zollinger-Ellison syndrome CHRISTINE G.THOMSON, I. G. M. CLEATOR, AND W. SIRCUS

Abnormal metabolism of secondary bile acidsin patients with cirrhosis Z. R. VLAHCEVIC,I. BUHAC, C. C. BELL, JR., AND LEON SWELL

Liver in haemoglobin H disease CHEW BENGKENG AND TAN KHENG SHOO

Cholelithiasis: A clinical and dietary surveyMARY WHEELER, LOIS LOFTUS HILLS, AND BETTYLABY

Failure of the human rectum to absorb electro-lytes and water GHISLAIN J. DEVROEDE ANDSIDNEY F. PHILLIPS

Ultrasound in the diagnosis of malignant pan-creatic tumours G. ENGELHART AND U. W.BLAUENSTEIN

Progress ReportThe chemical composition and function ofgastrointestinal mucus J. SCHRAGER

Notes and activities

Copies are still available and may be obtained from the PUBLISHING MANAGER,BRITISH MEDICAL ASSOCIATION, TAVISTOCK SQUARE, w.c. l. price 17s. 6D.

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546 Notes and activities

Notes and activities

Sir Francis Avery Jones

Everybody who reads Gut, and especiallythose who have been concerned in theday-to-day work of producing the Journal,will receive with delight the news that thelast editor, F. Avery Jones, has beenknighted by the Queen for his services tomedicine, and to gastroenterology inparticular. In the March issue of GutDr Hunt wrote his praises and linkedthem with the rise and development ofour Journal, and a dinner in his honourand a presentation marked the event.All readers of Gut can now add theircongratulations to one who has done somuch through this medium and in manyother ways for this relatively new specialty.

American Gastroenterological Association:71st Anumal Meeting

The 71st annual meeting of the AmericanGastroenterological Association was heldat Boston in May 1970 under the Presi-dency of Stewart G. Wolf, with 1,575members and guests attending the meeting.It was preceded during the same week by a

two-day postgraduate course on 'Patho-physiology of the biliary tract: colon fromcanaliculus to Oddi', by the AmericanSociety for Gastrointestinal Endoscopyand by splinter meetings on 'Gastro-intestinal immunology', a teaching and

training seminar, and the Gullet Club.Absorption, secretion, the liver, andmechanisms of enteric infection were thethemes covered by the Research Forum.The clinical symposia covered 'Oeso-phageal reflux', the 'Irritable colonsyndrome and diverticular disease', 'Clini-cal problems of nutrition', and 'Cancerdetection today and tomorrow'. Inaddition there were the two main plenarysessions, with the special lectures andselective short papers.The annual Memorial Lecture was

given by Professor W. D. M. Paton on the'Neurohumoral mechanisms of the smallintestine'. The annual DistinguishedAchievement Lecture was given byDr A. F. Hofmann (Rochester, Minnesota)on 'Function and dysfunction of the bileacids'. Professor Paton gave the Associ-ation afascinating picture of the pharmaco-logical techniques which he had developedfor the study of the neuromuscularmechanisms of the intestine, and illustrat-ing the mode of action of drugs on thealimentary tract. Dr Hofmann gave, asanticipated, a brilliant lecture on therole of bile acids in health and disease,illustrating how chemical structure deter-mines physical properties and how thesein turn determine physiological activity.The mechanisms of fat absorption and therole of the enterohepatic circulation, withthe interplay between hepatic function,intestinal absorption, and bacterial de-generation of bile salts, were explainedwith exceptional clarity, and their practicalapplication in malabsorption states illus-trated.The Presidential Address gave the

Association a prospect of research at anew Marine Bio-medical Institute, wherethe study of marine life offers a possibilityof working out the biochemical evolutionin the history of Man. This was mostappropriately illustrated by the 1969student research prizewinner, Mr H. I.Levene, who studied the presence of Yand Z proteins in liver hepatocytes and hadshown, with studies on bromsulphthaleinexcretion, that their appearance in theevolutionary scale corresponded with thetransition from sea to land. Whenexcretory function of the gill membranewas lost alternative routes had devel-oped for excretion of organic anions.

1-ALIMENTARY ASPECTS

There were a number of papers on smallintestinal activity and the malabsorptionproblem. S. E. Goldfinger, W. D. Heizer,and T. W. Smith (Boston) showed thatdigoxin is poorly absorbed in non-tropical sprue, hypermotility syndromes,and after intestinal resection, but does notcorrelate with the degree of steatorrhoeaor xylose excretion. Absorption wasunaffected by complete biliary exclusionand represents a mucosal insufficiency. A

therapeutic advance arising from thisstudy may be the demonstration thatcholestyramine interrupts the entero-hepatic circulation of digoxin and can beused to treat digitalis intoxication.

R. K. Crane, P. Malathi, W. F.Caspary, and K. Ramaswamy (NewBrunswick) reported studies which sug-gested the presence of two interacting,but separate, monosaccharide transportsystems in the brush border membrane ofthe hamster small intestine. One acceptsglucose only from disaccharide and isnovel. The other accepts free mono-saccharides added to the medium, orreleased by hydrolase activity, and is awell known Na+-dependent system.D. H. Alpers, W. P. T. James, J.

Gerber, and K. J. Isselbacher (Missouriand Boston, Massachusetts) describedwork done on the turnover of intestinaldisaccharidases and brush border proteins.This work provided no evidence of adifferential turnover of lactase comparedwith other disaccharidases, as an explan-ation for the low levels of lactase foundin the adult rat.

J. Giller and S. F. Phillips (Rochester,Minnesota) described a new technique forsampling ileal contents for 24 hours,using a perfusion technique on normalindividuals and in patients with non-tropical sprue. The method enables studiesto be made differentiating the role of thesmall and large intestine in the productionof diarrhoea. The amount of water, Na, K,Cl absorbed by the colon could bemeasured by this technique. The studysuggested that more electrolytes and waterenter the colon than previously suspected,and colon absorption, concomitantly,was greater. The mean figures were H20:1,428 ml, Na: 183 m-equiv, K: 4.2,Cl: 100 m-equiv per day. In sprue, ilealwater and electrolytes were increased:despite greater colonic absorption than inhealth; faecal values were also elevated.

J. G. Banwell, Sigorbach, R. Mitra, andN. F. Pierce (Calcutta, India) have foundpathogenic E. coli in the alimentary tractin patients with acute diarrhoea and inwhom none of the normal pathogens havebeen isolated. The serotype isolated ofE. coli, 015 Hl1, produced an exotoxinand, when studied in isolated animal loops,produced fluid secretion in many wayscomparable to that caused by the choleraexotoxin. Not all cases had a single sero-type and some had a mixed infection, withvarious serotypes present. Fluid outputwas usually greater in the jejunum thanthe ileum, and with unidirectional passageof Na and HCO3 this provided furthersupport for the recently reported patho-genic E. coli serotype which had beenfound in adult cases of traveller's diarrhoea,although this particular serotype had notbeen found in the present series. Itprovided important evidence linking thefilterable exotoxin which has been found

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547 Notes and activities

with the cholera vibrio with these E. coliinfections.A whole session was devoted to the

mechanism of enteric infections, particu-larly the problem of transfer of drugresistance, factors responsible for virulence,and the biological effects of cholera toxin,which were all reviewed in depth byStanley Falkour, Samuel B. Formal, andCharles J. Carpender. The importantrecent advance is the reduction of theenormous fluid loss by giving oral glucosesolution; the effect of the cholera toxinon the cyclic AMP was shown.The lower oesophageal sphincter seemed

to have gained ascendancy over the intra-abdominal oesophagus in the role ofcountering gastric reflux into the oeso-phagus, and the emphasis was on theeffect of gastrin and secretin on loweroesophageal sphincter activity, gastrincausing increased tonus, and secretinacting as the 'entero-gastrone of the loweroesophageal sphincter' and acting as areversible competitive inhibitor, accordingto the elegant studies by Sidney Cohen andWilliam Lipshutz of Philadelphia. As DrCode pointed out in discussion, thehousehold remedy, sodium bicarbonate,for heartburn, not only reduced aciditybut in so doing influenced the lower oeso-phageal sphincter by the reduction ingastrin and stimulation of secretin. L. A.Hootkin, L. J. Benz, S. Margulies, R. T.Canthorne, and T. R. Hendrix (Baltimore)studied 50 subjects (29 with and 21 withoutsymptoms) prospectively to determinewhich diagnostic procedures best correlatewith the historic low pain impression ofchronic gastrooesophageal reflux. Allunderwent study by oesophageal acidperfusion (Bernstein test); pH probedetermination of gastrooesophageal refluxof acid, defined as fall in intraoesophagealpH to less than 4, after intragastricinfusion with 300 ml 0.1 M HCI with pHprobe position 5 cm above the uppermargin of the lower oesophageal sphincter;a measurement of mean resting loweroesophageal sphincter pressure (normalgreater than 9.5 mm Hg above intragastricpressure); and with cine radiography withneutral and acid barium consideredpositive if acid barium created a motilitydisturbance which was absent with neutralbarium and improved by administrationof antacid. From these studies it appearedthat the best correlation of symptoms ofgastrooesophageal reflux is the use of theBernstein test or pH probe. They notedthree individuals without any evidence ofreflux who had abnormal sensitivity of thelower oesophagus to acid. They also notedthat positive tests became negative aftertreatment with antacids. In reply to aquestion from the Chairman, only veryfew people held up their hands to indicatethat they had never experienced symptomssuggestive of acid reflux!

S. Baum, M. Nusbaum, and H. J.

Tumen (Philadelphia) gave an account of of the Liver and the American Gastro-the use of pitressin given by selective enterological Association and also in amesenteric arterial infusion, often over two-day postgraduate course entitledseveral days, for the control of gastro- 'Patho-physiology of the biliary tract;intestinal haemorrhage. Thirteen patients from canaliculus to Oddi', which waswith variceal bleeding who had been so held at Wentworth-by-the-Sea, Ports-treated were controlled by the infusion in mouth, New Hampshire, some 50 milesall but one case. In five, the bleeding from Boston. Over 400 people attendedceased promptly, giving ample time to this course, which preceded the mainprepare for subsequent shunt. In three meeting and took place in a most pictur-patients, it was necessary to obtain esque New England seaside hotel.haemostasis by continued perfusion for J. L. Boyer, M. Hales, and G. Klatskinfive to seven days. In four other patients, (Yale) described four patients with portalperfusion controlled bleeding, but opera- hypertension of pre-sinusoidal type due totion was not undertaken. The same tech- focal obstructive lesions, demonstrable atnique was used in a few patients with necropsy by vinylite corrosion casts inbleeding from gastric ulcer or erosive three at the junctions of the right and leftgastritis, and with success. No cardiac or intrahepatic portal veins and in the fourthother adverse reactions had been noted. in more distal portal vein radicles. TheThe pitressin was given at the rate of 0-2 extrahepatic portal vein showed intimalunits per ml of glucose solution per thickening in all four patients, a calcifiedminute, reduced to 01 unit in some. plaque in one, and a non-obstructiveOne paper which escaped the main localized mid-line web in another. Splenic

plenary session, but which may perhaps venography was normal except for abruptprove to be the outstanding contribution cut-offofintrahepatic portal vein branches(however, with the complexities of in two. The condition was a rare one butimmunological techniques, itclearlyneeded was probably the same as the idiopathicfurther study), appeared in the symposium portal hypertension seen in Calcutta, and aon cancer detection. Philip Gold des- similar syndrome with organizing thrombicribed the very encouraging results he in the portal veins, described by T. B.had obtained in the correlation of colon Reynolds and his group from Los Angeles.cancer with his carcino-embryonic antigen. The location and extent of the lesionsThe high spot of the meeting of the suggested that the syndrome of non-

American Society for Gastrointestinal obstructive or idiopathic portal hyper-Endoscopy was the Roche lecture, tension is attributable to organized intra-delivered by Dr Itaru Oi, on 'Fibre- hepatic portal vein thrombi. Aetiologyduodenoscopyandendoscopicpancreatico- was unknown although two patients gavecholangiography'. This was a remarkable a history of 'missed' appendicitis.tour de force, with a very clear visualiza- E. Goeser, T. London, A. Sutnick,tion of duodenal ulcers and also the B. Blumberg, and J. Senior (Philadelphia)pancreatic papilla. A striking moving of had tested donor blood collected duringbile secretion from the papilla was 1969 from twolarge Philadelphia hospitals.shown and the technique of pancreatico- Thirteen of 3,847 units (0.34°/0) from thecholangiography, with cannulation of the University of Pennsylvania Hospital hadduct, was described. The value of this detectable Australia antigen, whereas 45was demonstrated with carcinoma of the units of 2,791 (1.6 %) collected from thepancreas and also in the diagnosis of Philadelphia General Hospital containedchronic pancreatitis. It is to be noted that the antigen. The latter, a large publicelevation of serum amylase followed hospital, had used blood collected fromcannulation and retrograde radioopaque prisoners and their relatives where thedye injection. The instrument used is at incidence of a positive test was 310%.present still in prototype form and not yet Although efforts had been made to avoidavailable for purchase, but in due course using blood containing the antigen, 33it will clearly prove of very considerable positive units had been transfused. Duevalue in the diagnosis and assessment of to death of the patient or difficulty intreatment of duodenal ulcer and of follow up, only 14 recipients were followedpancreatic and biliary tract disease. The closely; eight did not develop any illnessinstrument is a long, particularly flexible but six did develop hepatitis, five anictericfibre-optic endoscope, with a short head and one icteric. The incubation periodwhich can be angulated and also rotated could be surprisingly short, the rangealong the longitudinal axis, and carries being from 19 to 103 days. The administra-both light and cannulation ports. tion of Australia antigen-negative blood

F.A.J. did not prevent the development ofhepatitis, for four of 27 recipients ofnegative Australia antigen blood developedhepatitis, all with a short incubation

HEPATO-BILIARY ASPECTS period of some three to four weeks.Papers on these subjects were given in the C. M. Lewis and I. M. Arias (Newmain meeting in Boston under the auspices York) found previously unsuspectedof the American Association for the Study Dubin-Johnson syndrome in 18 women

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548 Notes and activities

who becamejaundiced while takingvariousoral contraceptives and 15 who becamejaundiced during pregnancy. Diagnosiswas confirmed in 24 patients by liverbiopsy and in 30 by conventional liverfunction tests, including oral cholecysto-graphy, which showed a non-filling gall-bladder, and estimates of BSP excretory(T..) and relative storage capacity (S) bythe method of Wheeler. The delayed(210 minute) rise in serum bromsulph-thalein expected in Dubin-Johnson syn-drome was absent in 25 % of the patients.Serum cholesterol, alkaline phosphatase,and 5-nucleotidase levels were normal.Family studies of eight of these womenre\ ealed 12 additional cases. Pregnancyand oral contraceptives converted themild hyperbilirubinaemia of this syndromeinto overt jaundice, often resulting indiagnostic and therapeutic problems. It isbelieved to be a selective hepatic excretorydefect of uncertain inheritance withoutchemical or morphological signs ofcholestasis.

J. C. Kniffen (Gainesville, Florida)discussed a most interesting patient witherythropoietic protoporphyria. This con-dition is marked by stasis of proto-porphyrin in the portal zones and otherparts of the liver leading to portal fibrosisand portal hypertension. The proto-porphyrin is excreted exclusively throughthe liver and a portion is reabsorbed,providing an enterohepatic circulation.Cholestyramine was given to impair theenterohepatic circulation and iron wasadded when clinical iron deficiencydeveloped. Photosensitivity abated andred cell plasma and faecal protoporphyrinmarkedly decreased. After 13 monthsof therapy a second needle biopsy of theliver was done and showed a strikingdecrease of protoporphyrin. This treat-ment may prevent progression of portalfibrosis and portal hypertension insuch patients.

R. P. Soloway, A. H. Baggenstoss,L. R. Elveback, J. L. Schoenfield, B. L.Stubbs, and W. H. J. Summerskill, fromthe Mayo Clinic, reported preliminaryresults of a beautifully planned doubleblind trial of prednisolone and azothio-prine therapy in chronic active liverdisease. Patients were selected if theillness was of more than 10 weeks'duration, liver biopsy had been performed,and there was persistent 10-fold elevationof SGOT or five-fold increase of SGOTwith two-fold elevation of serum gammaglobulin. Forty-one patients had beenobserved for periods of three months tothree years. There were 15 patients in theprednisolone (20 mg/day) group, 13 inthe azothioprine (100 mg/day) group, and13 in the control. Subjective improvementwas the same in all groups. There was onedeath in the placebo group, four in theazothioprine, and none in the predni-solone-treated patients. Currently, the

prednisolone group show significantadvantages (P / 005) in decreasing bili-rubin, SGOT, gamma globulin, and piece-meal necrosis compared with the othergroup. It wasconcluded that drugtreatmentin relation to placebo had not, so far,significantly influenced the initial coursebut early biochemical and histologicalimprovement occurred with prednisoloneand the therapeutic efficiency of azothia-prine alone was currently suspect.

G. D. Cain, G. Mayer, and E. A. Jones(London) had measured the albumin andfibrinogen metabolism in eight patientswith hepatocellular disease before andafter prednisolone therapy. The meanplasma albumin and fibrinogen con-centrations and albumin and fibrinogensynthetic rates were all lower than thecorresponding values in a group of controlpatients. Prednisolone therapy was associ-ated with a significant increase in theplasma concentration and synthetic rateof albumin without appreciably changingthe intravascular albumin pool. Changesin the plasma concentration, intravascularpool, and synthetic rate of fibrinogenwere small and inconsistent. The data arecompatible with the selective action ofcorticosteroids on hepatic protein meta-bolism and with the existence of dffer-ent mechanisms for the control ofalbumin and fibrinogen synthesis.During the course of a clinical sym-

posium on cancer detection, E. Alpert(Boston) discussed the use of seruma-feto-globulin estimations in the diagnosisof primary liver cancer. In the UnitedStates, the protein was present in 26-6%Caucasians and 62-1 % of non-Caucasianswith primary liver cancer. Results seem tocorrelate with the size of the tumour andwith its degree of anaplasia. Survival wasinversely related to the presence of thefetoglobin, being 120 days in those with apositive test and 240 days in those without.

Bile formation and gallstonesH. 0. Wheeler (San Diego) discussed thesecretion of water and inorganic electro-lytes into the bile. This was by a process ofactive transport of solute rather thanpumping. The transport maximum of bileacids is very high and this is the majorosmotic force for the production of bile.Bile flow is mainly bile-salt dependent, butthis is not the whole story, for there isconsiderable absorption and secretion ofwater and electrolytes taking place in theduct system itself. Following this up,N. B. Javitt (New York) thought that incholestasis there was failure of bile saltsecretion and hence of water flow into thebile. W. G. M. Hardison (Chicago)emphasized the importance of bile saltsin the biliary secretion of phospholipid.This is necessary for the bile salt-phospholipid-cholesterol micelle to format the biliary canaliculus. E. H. Mosbach

(New York) had found evidence of anegative feedback mechanism of hepaticbile acid synthesis depending on theamount of bile acid reaching the liver inthe portal vein.

J. M. Diamand (Los Angeles) describedelectron-microscopical studies on theconcentrating capacity of the gallbladderbile. Each gallbladder epithelial cell isadjacent to long, narrow, dead-end lateralspaces. Sodium chloride is actively trans-ported into these spaces and water follows,the sodium chloride then passing into theopen (vascular) end of the space and sointo the blood.

Lithogenic bile is bile which has a lowratio of bile acidsand lecithin to cholesterol.J. L. Thistle and L. G. Schoenfield, of theMayo Clinic, measured these biliaryconstituents in duodenal bile collectedafter cholecystokinin administration fromArizona Pima Indian women who have a50-70% prevalence of gallstones. The ratioof bile acids and lecithin to cholesterolwas greatly reduced and the bile com-position, when plotted on triangularcoordinates, was in the zone of super-saturation for cholesterol. These authorshave previously shown that in Caucasianwomen with gallstones, chenodeoxycholicacid would augment the cholesterol-solubilizing properties of bile and thatcholesterol crystals were eliminated. Gall-stones were dissolved according to theirsize, small stones taking 50 days and largeones up to 1,000 days. They now suggestthat analysis of duodenal bile may be ofvalue in assessing prophylactic treatmentwith bile acids and also in investigatingpredisposition to gallstones and familialpatterns of cholelithiasis.

L. Weinstein (Boston) discussed the useof antibiotics for cholangitis. Ampicillinis concentrated from the blood into thebile. T-tubes and cholecystectomy inter-fere with its efficacy. Very large doseswere suggested, up to 14 g a day for thetreatment of patients with bacterialcholangitis. Aureomycin is the tetracyclinebest concentrated in bile but should begiven with caution for hepatotoxicity mayfollow more than 2 g a day intravenously.

S. Sherlock (London) believed thatmany obscure cases of prolonged chole-stasis could be diagnosed preoperatively ifneedle liver biopsy, serum mitochondrialantibodies, and percutaneous cholangio-graphy were more frequently performed.She illustrated this by a series of patientswith carcinoma in the region of the mainbile ducts which had been missed atoperation, but which could have beendiagnosed had these tests been performed.

S.S.