Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
Gut, 1987, 28, A1328-A1412
The British Society of Gastroenterology
The Jubilee Meeting of the British Society of Gastroenterology was held in the University of London on 15-18 September 1987 under the Presidency of Mr John Alexander-Williams. Below are printed the abstracts of the 364 oral and poster communications selected for presentation at the meeting.
Hospital, London, and Amersham Inter- paratuberculosis and M avium. Restricted INFLIAMMATORY BOWEL DISEASE national, Bucks) "'Indium labelled leuco- total DNA from a CD mycobacterial cytes are an accurate means of detecting bacillary isolate was used to generate a Enteral nutrition in severe colitis inflammation, particularly inflammatory genomic library in pGEM-1. Resulting bowel disease (IBD). Tc 99m as an alterna- specific cloned DNA probes precisely dis- SS C RAO, C [) HOLDSWORITH, ANI) A R W tive radioisotope offers advantages of con- tinguished different mycobacteria on the FORREST (Gastroinitestinial U,iit and Depart- venience, lower radiation dose, and basis of restriction fragment length poly- meait of Clinical Chemistry, Royal Hallam- theoretically higher image resolution. A morphisms (RFLP). A novel insertional shire Hospital, Sheffield) Small intestinal new Tc 99m chelate, HMPAO (hexamethyl element of about 1-5 kb (pMB22) was absorption and tolerance of enteral nutri- propylene amine oxime) is a moderately identified, repeated 1()-20) times through- tion was assessed prospectively in nine efficient leucocyte label with selectivity for out the mycobacterial genome. DNA patients with severe colitis. After admis- neutrophil leucocytes. We evaluated restricted and probed with pMB22 gave a sion, the patients were starved for 24 hours abnormal scans after reinjections of auto- multiple banding pattern RFLP identical in during which stool output was collected. logous Tc 99m HMPAO leucocytes in 32 the DNA from each of three independent Thereafter 2 I/day of Fortison standard subjects with proven or suspected IBD. The CD, and three Johne's disease M para solution was given enterally via a fine bore normal distribution of radioactivity is isolates, but not other mycobacterial DNA tube for six days, after which patients ate a similar to that seen with indium labelled suggesting a specific relationship between normal diet. During enteral feeding, a 5 g d cells, with additional activity in urine soon this insertional element and pathogenicity. xylose test and a five day faccal fat estima- after injection, and some bowel distribution Similar studies on nanogram quantities of tion were carried out. Stool output, symp- in normal subjects after four hours. DNA from one CD spheroplast isolate tom scores, daily weight, Hb, ESR and
Occasional activity in the gall bladder indi- using a novel cloned DNA probe for Mpara http://gut.bmj.com/ albumin were also monitored throughout cates that this normal bowel activity follows 16S ribosomal RNA identified the sphero- the 10 day study period and prednisolone biliary excretion of free complex. Bowel plasts as mycobacterial but distinct from any sulphate was given intravenously. One hour activity resulting from labelled neutrophil known mycobacteria so far examined. blood xylose and five hour urinary xylose migration to inflamed areas could be identi- Crohn's disease derived mycobacterial values were normal in all except one patient fied much earlier than four hours, however, isolates appear heterogenous. with Crohn's disease. Fat absorption was and as a result IBD could be confidently normal in every patient. In spite of enteral diagnosed. Twenty five of 32 patients had feeding, there was a significant reduction in abnormal scans showing inflamed bowel. stool weight (p<0)(01) and stool frequency The resolution of small bowel involvement Adhesion of colitic E coli (EC) to isolated on September 26, 2021 by guest. Protected copyright. (p<0O001) over the 1i) day period. There is clearly superior to that with indium leuco- human colonocytes was a signiticant improvement in symptom cytes. No false positives or false negatives scores (p<0(0l), ESR (p
7he British Society of Gastroenterology A1329
mean=0-33 compared with a mean of 0-1 J ALEXANDER-WILI-IAMS (T/ic Gen1eral required a further 14 SP between 12 and 36 for control EC is significantly higher, Hospital, Birmingham) From a series of 59 (median 18) months after the initial SP. All p (0001. Buccal epithelial cell adhesive patients with enterocutaneous fistulae com- but one of the previous SPs were patent. No ability correlates with both the BB adhesion plicating Crohn's disease, 31 occurred in 23 postoperative complications arose from the index and the BB/BL ratio, p=0)001. This patients within a month of operation. SP sites. Intraperitoneal abscess developed study shows that colitic EC have a greater Four were referred having presented the in one patient from a duodenal leak. Our ability to adhere to human colitic colon than fistula within 10 days of appendicectomy by further experience indicates that SP is an controls. The higher BB/BL ratio for colitic surgeons inexperimented in Crohn's effective and safe procedure which has a EC suggests that adhesion is specifically disease. All were ileocutaneous, three had place in minimal surgery of both active and directed to the brush border. These data resection and one a stricturoplasty; all inactive CD, provided no distal obstructing support the view that EC may have a role in resolved. lesions are overlooked. the pathogenesis of this disease. Suture line leakage accounted for 18 fistulae and nine, presumed to be caused by operative trauma, originated from a dis- Delayed-release 5-aminosalicylic acid sected area of gut not affected by Crohn's (5-ASA) and sulphasalazine (SSZ) in the disease. Previous reports suggest that the treatment of mild to moderate ulcerative majority of such fistulae will heal spontane- colitis (UC) relapse ously. In this series, however, only 12 of the I IVER 27 resolved without further operation. S A RIl EY, V MAN!, M J GOODMAN, AND L A The principal predisposing factors in Effect of hepatic artery embolisation on I URNBER(G (University Departmenit of suture line leakage were adjacent septic survival in carcinoid syndrome Medicine, Hope Hospital, Salford; Leigh foci, hypoproteinaemia and colonic anasto- Infirinary, atid Bury General Hospital, mosis. In some severely compromised M COUPE, A HEMMiN(iWAY, Ii J F HIODGSON, Manchester) Sulphasailazine is of benefit in patients a primary stoma with delayed ANI) 1) J AL ISON (Depis of Medicine antd( UC relapse but side effects may limit its use. anastomosis might avoid leakage. Radiology, Royal Postgraduate Medicial 5-ASA appears less toxic. We have there- In another series of patients having exten- School, Hammersmith Hospital, Lonidon) fore compared SSZ, equivalent dose 5-ASA sive dissections, occult operative trauma Hepatic artery embolisation relieves and high dose 5-ASA in mild to moderate has been rendered overt by CO, distension systemic hormonally mediated symptoms in UC relapse. of the gut and underwater inspection (cycle the carcinoid syndrome, and local symp- Sixty one patients (32M:29F, aged 20-78 tyre puncture manoeuvre). All such toms of hepatic pain. We documcnt here the years) were randomly allocated to either detected bowel breaches have been sutured effect of this procedure on survival in a SSZ 2 g, 5-ASA 80X) mg or 5-ASA 2-4 g daily without subsequent fistulae. We suggest retrospective survey of 63 patients with in a double blind four week trial. One that routine adoption of the insufflation carcinoid syndrome seen in one centre over http://gut.bmj.com/ patient defaulted leaving 19 SSZ, 20 5-ASA manoeuvre might have prevented five of the 10 years. Twenty four underwent hepatic 80X) mg and 21 5-ASA 2-4 g for analysis. nine operative trauma fistulae in this series. artery embolisation, and in a further six Groups were comparable for age, sex, embolisation was intended, but technically cxtent of disease and pretrial SSZ intake. not feasible (portal vein obstruction or Six patients were withdrawn, four SSZ (two Strictureplasty for Crohn's disease - a nine inadequate arterial access). The indication deterioration, two side effects) and two year experience for embolisation was severe systemic symp- 5-ASA 2-4 g (deterioration). toms poorly controlled by pharmacological
Within treatment comparisons revealed [F C B DEIIN, N J MCN MORIENSEN, M G W therapy, or marked local pain. Ovcrall, in on September 26, 2021 by guest. Protected copyright. significant improvement of (a) sigmoido- KETI LEWELL, 1) P JEWE.LL, AND) THIL .AlAE E C G those patients followed to death, the mean scopic grade in the SSZ group, (b) rectal LEIE (John Radcliffe Hospital, Oxford) The survival from symptom onset was longer in bleeding and sigmoidoscopic grade in the role of strictureplasty (SP) is controversial those undergoing hepatic artery embolisa- 5-ASA 800 mg group and (c) stool fre- in the management of obstructive Crohn's tion, but this was not statistically significant quency, rectal bleeding and mucus and disease (CD). In Oxford, since 1978, 2(0 (58-7±9.7 (SEM) months n= IX v449+59-6, sigmoidoscopic grade in the 5-ASA 2-4 g patients have undergone 26 SP operations n= 1 1). A more accurate comparison can be group. Symptomatic remission occurred in with a median follow up of 30 (range 2-102) drawn between those patients successfully 2 SSZ, 300o 5-ASA 80X) mg and 42% months. Crohn's disease had been present embolised, and those in whom the pro- 5-ASA 2-4 g (p<0.05 v SSZ). from 0-240 (median 12) months. Sixteen cedure was unsuccessful, comparing sur- Greater improvement of rectal bleeding patients previously had resections for CD. vival from the angiographic procedurc. occurred in the 5-ASA 2-4 g than SSZ group Eighteen patients received high dose There was no difference in survival between (p<(-(05). Side effects, however, were parenteral steroid therapy preoperatively. these two groups (embolised mean 18.0+ similar in the three groups. Strictures were confirmed before surgery by 3-26 months n= 18 v embolisation technic- High dose 5-ASA is more effective than small bowel enema and identified opera- ally impossible mean 19-6±6-5 months SSZ in the treatment of UC relapse. tively by intestinal intubation. The median n=6). This study confirms that the hepatic number of strictures identified at surgery artery embolisation does not prolong sur- was two (range 1-17): 16 patients had one vival in the carcinoid syndrome, despite its Causes and prevention of postoperative SP, 10 patients between two and seven SP. effectiveness in relieving symptoms. fistulae in Crohn's disease The length of stricture plastied bowel ranged from 1-17 (median 3) cm. Intestinal FRANCOISE IIEYEYN, M C WINS! LT, HILARY resections were performed concurrently in Cellular chemotaxis to bile after liver trans- ANDRE.WS, R N Al.lAN, M R B KEIGHI LY, AND 12 patients. Four patients subsequently plantation Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
A 1 330) The British Society ofGastroenterology
[) Ii ADAMS, D BURNEFn, R A STOCKLEY, AND 5 and 12 ,tm sections with an indirect Portal tract lymphocyte populations in E EI.IAS (Liver Unit, Queen Elizabeth immunofluorescence technique. CGRP and primary sclerosing cholangitis Hospital, Edgbaston, Birmingham) The substance P containing fibres were identi- mechanisms of cell recruitment to liver fied within portal tracts in the livers of both J A SNOOK, K A Fl.RMING, A HERYET, P KELILY, allografts during rejection are poorly under- species. Fibres were most frequently seen D P JEWEILL, AND R W CH{APMAN (Department stood. Chemotactic factors may be impor- around hepatic artery branches but were of Gastroenterology and Nuffield Depart- tant but have not been studied in man. As also seen in close proximity to bile ducts and ment of Pathology, John Radcliffe Hospital, the cellular infiltrate is centred on bile ducts portal vein branches. No intra-acinar fibres Oxford) Recent evidence suggests that we have looked for chemotactic activity in were identified. There was abrogation of immunological mechanisms may be of serial bile samples from 13 liver transplant staining for both peptides in the livers of rats importance in the pathogenesis of primary recipients. treated in the neonatal period with the sclerosing cholangitis (PSC). We have pre- During nine episodes of gratft rejection, sensory neurotoxin capsaicin. These results viously shown that patients with PSC have bile became chemotactic for both neutro- indicate that the intrahepatic vasculature reduced numbers of CD8 cells in peri- phils and mononuclear cells when com- but not the liver parenchyma receives a pheral blood. Here, portal tract lymphocyte pared with bile taken from seven stable peptidergic sensory nerve supply. subsets have been analysed in cryostat sec- transplants (neutrophils rejection: range tions of liver biopsies using monoclonal 2 2-22, median 4*2xcontrol; stable: 0(44- antibodies and an immunoperoxidase tech- 2-7, median 1-73; p<0)t)05: monocytes nique. Liver biopsy sections from nine rejection: 0-89-7-03, median 2 12; stable: patients with precirrhotic PSC, nine 0(55-2-63, median 1 08; p<0).025). Management of increased cerebral blood patients with primary biliary cirrhosis Bile taken two to four days before clinical flow in patients with fulminant hepatic (PBC) and seven patients with histologic- rejection was chemotactic for lymphocytes failure ally normal livers were examined. The T (2-3-8 9, median 3-2; p<0 (X)I) but during lymphocyte was the predominant portal clinical rejection inhibited chemotaxis R J EDE, C D GOVE, AND K WILLIAMS (Liver tract mononuclear cell in all three groups. (0( 144- 108, median 0(74, p<0.025) when Unit, Kings College Hospital and Medical Mean total T lymphocyte counts per portal compared with bile from stable transplants School, London) Raised intracranial tract (+/-l SD) were increased in both PSC (0.97-1-8, median 1.4). pressure (ICP) is a major cause of mortality (173+/-105) and PBC (210+/-110) com- We conclude that (1) chemotactic factors in patients with fulminant hepatic failure pared with controls (42+/-27). Similar are important in cell recruitment to reject- (FHF) and is generally attributed to the increases were seen for both CD4' and ing liver grafts. (2) Lymphocytes are development of cerebral oedema which is a CD8 cells so that the CD4t :CD8' ratio was attracted to the graft before the onset of frequent autopsy finding. It had been sug- 1-49 in PSC, 189 in PBC and 1 63 in clinical rejection. (3) During clinical rejec- gested recently that ICP might also be controls. In contrast, B lymphocyte counts http://gut.bmj.com/ tion lymphocyte chemotaxis is inhibited increased as a result of dilatation of the were low in PSC (8+/- 14), PBC (9+/- 14) whereas other cells are attracted to the cerebral blood vessels resulting in increased and controls ( 1+/- 1). These results suggest graft. cerebral blood flow (CBF). We therefore that T cell mediated immune mechanisms determined CBF using the iv '-"Xe clearance may play an important role in the patho- technique in 15 patients with FHF caused by genesis of PSC. In contrast with the situation paracetamol overdose (10), viral hepatitis in peripheral blood, the portal tract CD4': Distribution of calcitonin gene related (three), and halothane hepatitis (two). CDSt ratio is similar in PBC and PSC. peptide (CGRP) and substance P-containing Patients were studied in grade four nerves in liver: an immunohistochemical encephalopathy after intubation and on September 26, 2021 by guest. Protected copyright. study mechanical ventilation. In every case CBF was increased with a mean value of 201 Changes in the hepatic haemodynamics with A [) BURT, M GilL ON, E WISSE, J M P0l.AK, AND ml/100 g brain/min (range 137-310) over a the development of liver metastases R N M MaCSWEEN (University Department oJ PaCO. range of 4-5-6-0 kPa (Cf normal Pathology, Western Infirmary, Glasgow, value of < I 10 ml/min). Cerebral blood flow D M NOi-l, S A JENKINS, S GRIME, J YAIES, D W Lab for Cell Biology anid Histology, Free values did not differ significantly between DAY, J N BAXTER, AND I G COOKE (University University ojf Brussel.s (VUB), Belgium, the three main aetiological groups. Departmenits of Surgery, Pathology anid Department of Histochemistry, Royal Post- Cerebral autoregulation in response to Nuclear Medicine, Royal Liverpool graduate Medical School, Lonldon) We have changes in PaCO. was assessed in seven Hospital, Liverpool) The ratio of the investigated the distribution of nerve fibres patients: CBF increased linearly over the hepatic artery flow (HAF) to total liver containing the regulatory peptides, calci- PaCO. range 2-5-7.5 kPa in all but one blood flow measured by dynamic scinti- tonin gene related peptide (CGRP) and patient in whom this autoregulatory graphy, the hepatic perfusion index (HPI), substance P in guinea pig and rat livers. response was lost a few hours before death. is reported to predict the presence of occult These peptides are closely associated with Raised CBF was reduced by vigorous liver metastases in patients with colorectal afferent neurones in the peripheral nervous hyperventilation and more rapidly by iv carcinoma. The aim of this study was to system. The livers of Dunkin Hartley Althesin (we have shown that both these determine the mechanisms responsible for guinea pigs and Wistar rats were perfusion measures reduce increased ICP in FHF). the alteration in the HPI with the develop- fixed with 04%, parabenzoquinone. Tissue These data indicate that increased CBF ment of micrometastases. Metastases were blocks were washed in 15%, sucrose and contributes to raised ICP in patients with induced in rats by an intraportal injection of frozen in liquid nitrogen. Polyclonal rabbit FHF and have important therapeutic impli- 8x 10( Walker carcinosarcoma cells. anti-CGRP and anti-substance P antibodies cations for the management of patients with Animals were studied at two, four, and six were used at dilutions of 1:200 to 1:800 on this life-threatening complication. days post inoculation. The HPI was Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
The British Society ofGastroenterology A 1 33 1 measured by dynamic scintigraphy and membranes from 154±16 (mean±SEM) to effect of cimetidine (1()t) mg/h iv for four hepatic artery flow (HAF) and portal 77+ 10 nmol O0/10' cells/min n=9, p<0 01. hours) on circulating SLI levels basally anid venous inflow (PVI) using '7Co micro- Pre-exposure to equimolai cysteine signifi- with ingestion of a mixed meal. In some spheres. Intrahepatic arteriovenous shunt- cantly reduced superoxide release to studies, intragastric pH was measured ing (HS) was determined after an hepatic 94± 12, n=9, p<0-01. A further reduction radiotelemetrically and either O)-1 N HCI or artery injection of FTc"' labelled macro- occurred when in molar excess (penicilla- 0(9%/o NaCI infused intragastrically. In aggregated albumen (4t) u). Micrometa- mine 33±7, cysteine 57±13, n=9). These further studies, an intraduodenal infusion stases were present at four and six days post agents could have potential benefit in limit- of fat was given with/without iv cimetidine. inoculation. The HPI at four days (51-80+ ing neutrophil stimulation in alcoholic Cimetidine (C) reduced meal stimulated 1-68; n=16) and at six days (67-81±3-38; hepatitis. SLI levels: meal alone: 83± I)0% min, mean n= 16) was significantly greater (p<0-001, integrated increment from basall, ±SE; Mann Whitney) than in normal rats (33-78± meal+C: 51±12% min, p<0()-5 (n=12). 1-77; n=20). Hepatic artery flow did not Measurement of pepsin synthesis in man Intragastric infusion of HCI ameliorated the change with the development of metastases using 1-'3C-leucine effect of C on mean postprandial gastric pH: but PVI was significantly decreased at six meal alone: 2-21; meal+C: 3-79; meal+C+ days (p<0-0)1) and was associated with a M E CORBETT, E J S BOYD, J G PENSIFON, K G HCI: 3-15; and prevented the cimetidine- significant increase in splanchnic vascular WORMSILFY, AND M J RENNIE (Departmnents of induced reduction in postprandial Sl I (SVR) and portal venous resistance (p< Physiology and Therapeutics, Dunidee levels. Meal alone: 75+ 18% min, meal+C: 0-001). At four and six days after inocula- University, Dundee, Scotland) We have 28±15% min, meal+C+HCI: 65±12'Y0 min tion HS was also significantly increased studied the effects of increasing doses of (n=6). Cimetidine did not affect the rise in (p<0(005). These results indicate (1) the pentagastrin (Pg) on gastric secretion of SLI levels during intraduodenal fat infusion HPI alters with the development of micro- acid, pepsin and total protein. In addition, (n=5). These data suggest that (1) cimeti- metastases secondary to decreased PVI, (2) we have used the rate of incorporation dine reduces postprandial SLI secretion the reduction in PVI is related to a rise of I-'`C-leucine into the YCA-insoluble indirectly by altering intragastric acidity, in hepatic vascular resistance consequent fraction of the gastric aspirate as an index of (2) intragastric acid is a factor regulating upon increased intrahepatic shunting. pepsin synthesis. nutrient stimulated SLI levels in man. On separate days 10 subjects received Pg 0, 0(25, 0.5, 1-0, 2-0, or 4-0 )tg/kg/h together with a primed infusion of '3C- Fat is a luminal stimulus for gastric somato- leucine 0-25 or t)*5 mg/kg followed by 0-25 statin release BASIC SCIENCE POSTERS or 0(5 mg/kg/h respectively. Infusions were continued for 210 min. Gastric juice was M R LUCEY, J DELVAILIE, AND YAMA[)A Penicillamine and cysteine inhibit acetalde- aspirated in 30 min batches. 'C enrichment (University of Michigan Medical C'enter, http://gut.bmj.com/ hyde induced superoxide production by the of plasma keto-iso-caproate was measured Ann Arbor, Michigan, USA) The mecha- neutrophil every 30 min. Affinity chromatography con- nisms regulating nutrient stimulated release firmed that "3C-leucine was incorporated of somatostatin like immunoreactivity A J K WIlTLIAMS AND RE BARRY (Department of solely into pepsin. (SLI) from the gut are unclear. We investi- Medicine, Bristol Royal Infirmary, Bristol) The dose of Pg required for half maximal gated the effects of fat and its constituents Acetaldehyde binds non-enzymatically to acid secretion was 0-13 tg/kg/h, and for half administered intra-arterially or intralumin- liver membrane proteins. We have shown maximal pepsin secretion was t) 10 [tg/kg/h. ally on SLI release from the isolated that penicillamine and cysteine will inhibit Incorporation of '-C-leucine into the TCA perfused rat stomach. Fat emulsion (micro- on September 26, 2021 by guest. Protected copyright. this binding, and that the product of this precipitate was linear with time, and the lipid), oleic acid and glycerol were adminis- binding will activate complement and rate was proportional to the plateau 'AC tered intra-arterially in three dilutions stimulatc the neutrophil both potential enrichment of plasma keto-iso-caproate. Pg (3x 10( 5, 3x 1) 4, 3x 10 ') in buffered per- mechanisms of cytotoxicity in alcoholic did not significantly alter from basal the rate fusate. Isoprenalin 10 SM was infused intra- hepatitis. of incorporation of '-3C-leucine into pepsin. arterially at the end of each experiment, a We have studied the effect of penicilla- These findings suggest that increased pepsin response exceeding 20)0% of basal levels mine and cysteine in modifying neutrophil secretion in response to increasing doses of indicating a viable preparation. In intra- superoxide release in response to acetalde- Pg is not caused by increased pepsin synthe- luminal studies, oleic acid and glycerol, hyde altered rat hepatocyte membranes. sis, but is attributable to recruitment of cells each diluted 10-fold in 0.9%0 NaCI and Liver membranes were preincubated in having similar synthetic activity. undiluted fat adjusted to pH 6, were admin- I mM acetaldehyde+equimolar or excess istered for three consecutive 10 minute (5/1 molar ratio) penicillamine or cysteine, periods. Neither intra-arterial fat, oleic acid pH 7-4, two hours, 18'C; washed and then Gastric acid regulates postprandial somato- nor glycerol stimulated SLI release at any exposed to neutrophils with superoxide statin release in man dose. Intraluminally administered fat release measured by cytochrome c reduc- increased SLI release in a time dependent tion in the presence or absence of super- M R LUCEY, P D FAIRCLOUGH, AN[) J A Hi WASS fashion reaching significance in the 3rd oxide dismutase. (St Bartholomews Hospital, London) The period. Period 1: 115±15% of basal Pre-exposure of the membranes to role of gastric acidity in mediating release of (mean±SE), period 2: 116± 1)%, period 3: equimolar penicillamine and acetaldehyde somatostatin like immunoreactivity (SLI) in 140)±12%, p<0-05, n=7. There was no significantly reduced superoxide release response to orally ingested nutrients in man increment in SLI response to either oleic compared to acetaldehyde alone exposed is uncertain. We studied in healthy men the acid or glycerol intraluminally. These data Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
A 1 332 The British Society of Gastroetterology suggest that (1) fat stimulates SLI release models but in vitro studies have been less chain, from a mean of 6-85 to 6 (p=0 01), from the isolated perf used rat stomach, reproducible. The recent innovation of syn- attended by a decrease of fucosyl groups, (2) this action is dependent on presentation chronisation of cell cultures with thymidine from a mean of 1-6 to 1-05 per chain of the stimulus to the lumen, (3) stimulation was used to study nine gastric or colorectal (p=(-02) in glycopolypeptides from the of SLI release by fat does not depend on its cell lines; no stimulation was seen with tumour site. Differences between mucus metabolism or absorption. pentagastrin or G17. Using the synchro- glycopolypeptides from non-malignant and nised assay, however, two cell lines showed uninvolved mucosa were small, and not an increase in growth rate (selenomethione statistically significant. These data show Mechanisms governing the biphasic pattern incorporation) to G17 10 [tg/l of 110 and that carbohydrate biosynthesis is curtailed, of gastric emptying after truncal vagotomy 120%. The most responsive of the cell lines and that biosynthesis of the polypeptide and pyloroplasty was xenotransplanted into mice and half the core may be abnormal, in mucus glyco- animals treated with G17 10 ug/day. Not all proteins produced at the tumour site in xenografts grew but of the five fastest grow- gastric cancer. N PARR, S GRIMtL, M CRITC iII IFY, J BAXTIR, AND the diameter of C MAC KI I (University Department of Surgerxi ing tumours in each group the tumours was significantly greater in the anid Depairtmnetnt oJ'Nuclear Medicinie, Royal Liverpool Hospital, Liverpool) After treated group by 17 days (p<0(0l). When N-methyl-N '-nitro-N-nitrosoguanidine truncal vagotomy and pyloroplasty (TV+ P) cells from this xenograft were cultured in (MNNG) induces changes in rat and human vitro a 148% increase in growth was seen. gastric emptying (GE) of liquids is biphasic, pepsinogen phenotypes with rapid early GE often producing post- We also studied the in vitro growth of vagotomy symptoms. Factors restricting freshly disaggregated human tumour cells J DEFIZE, J K DERODRA, AND R H HUNT this phase and provoking transition to the and showed a response to pentagastrin in (McMaster Untiversity, 1200 Maini Street W, one and colorectal tumours. This second, slow phase are unknown. We gastric -/4 Hamilton, Ontario, Canada) A character- investigated the contributions of small response was retained at in vitro passage 2 istic human pepsinogen (PG) phenotype bowel resistances, osmoreceptor feed back but lost by passage 6. Gastric and colorectal has been described in association with and sympathetic inhibitory reflexes to small tumours are often sensitive to gastrin in vivo gastric cancer and MNNG is known to - is often lost or in bowel distension. Sixty GE studies were this stimulation reduced produce gastric tumours in the rat. We in vitro cultures. done, using gamma camera imaging of describe changes in rat and human PG radiolabelled 15'Yo dextrose, on six dogs phenotypes, induced by MNNG in in vivo with TV+P and fitted with proximal duo- rat experiments and in in vitro cultures of denal cannulae. With the cannula closed Changes in mucus glycoprotein biosynthesis both rat and human chief cells. Rats were GE (%o) was initially rapid, followed by at the tumour site in gastric cancer fed MNNG or placebo for five different stasis (15 min 32±5-3, 60 min 34±4X8, time periods. PG phenotypes and histo- http://gut.bmj.com/ mean±SEM). Opening the cannula alone, N K DHIR, R L SIDEBOI IIAM, J SPENCER, AND logical status of the mucosa were deter- produced precipitous GE (76±4-2 TIIE LATE J SCHIRAGER (Department of mined from open biopsies taken under p<000 1, 88±2-6 p<0001 ANOVA). With Surgery, Roylal Postgraduate Medical anaesthesia before, during and after distal duodenal instillation of 15% dextrose School Hammersmith Hospital, Doi Cane MNNG. The fastest electrophoretic band at a rate equivalent to GE with the cannula Road, London) Immunochemical investi- decreased or disappeared as early as three closed, GE remained faster than in the gations and studies of cultured tumour cells weeks after MNNG. The changes, observed initial studies (50±7-0 NS, 65+6-8 p<0-01), have shown that carbohydrate biosynthesis in 17 of 32 rats, were permanent and con- but was slower than with diversion alone of mucus glycoproteins is altered in gastric sistently associated with gastric tumour on September 26, 2021 by guest. Protected copyright. (p<0-05). Normal saline instillation did not carcinogenesis. To extend these observa- lesions observed 10 months later (17 of 17). delay GE (78+ 10-6, 90+5.4). Finally, duo- tions we have examined the structures of Chief cells were cultured in the absence or denal instillation of 15% dextrose prior to mucus glycopolypeptides from non- presence of MNNG, which induced similar ingestion of the test meal caused slower malignant mucosa (20 specimens; indi- PG phenotype changes in both rat and initial emptying than in cannula closed viduals with benign peptic ulcer, or disease human chief cclls after 7-1) days. In human studies, without subsequent stasis (24±4-5, free), and from uninvolved mucosa (33 chief cells, a decrease of the Pg3 band, 47± 10(6). These results indicate that after specimens) or tumour site (32 specimens) in which is consistent with the 'carcinogenic' TV+P, small bowel resistances play a patients with stomach cancer. Carbohy- phenotype, was observed in two of six significant role in controlling GE. Osmo- drates and amino acids were measured by preparations, treated with MNNG. receptor responses persist after TV+P, but gas chromatography and autoanalysis. From We conclude that MNNG induced sympathetic inhibitory responses are not this, the weight of carbohydrate associated phenotype changes reflect mutations in the invoked. with representative polypeptide core seg- pepsinogen genes. The changes preceed ments of equal length was determined. gastric tumours and should be investigated A mean difference of 29%o (p<0.0001) as a marker for the early onset of gastric cancer. Gastrin - in vitro and in vivo studies in occurred between glycopolypeptides from gastric and colorectal cancer uninvolved mucosa and tumour site. This resulted from a reduction in numbers of (1) S WATSON, 1. DURRANT, D 1. MORRIS, AND carbohydrate chains, from a mean of 343 to Lactulose/mannitol: an ideal screening test CG GCEROUILAKOS (Departments ofSurgery and 276 chains/l100 amino acid units (p=0-0( ), for coeliac disease? (Cancer Research, University Hospital, associated with a decrease of serine and Nottingham) Gastrin is trophic for both threonine residues in the polypeptide core 1. D JUBY, J ROTHWELL, AND A T R AXON gastric and colorectal carcinomas in animal and (2) structural units per carbohydratc (Castroeenterology, Unit, The General Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
Tue Britisli Society ofGastroenterologyA A 1 333 InfirmarY, Leeds) Changes in intestinal lair weight (MW< l()12)000) accounting tor l)ivision, Al(lderlev P(ark, /Vlacclcsfield, permeability are shown by differential sugar 70-800 of the eluted counts. In contraist, (Cles/hire) Gastrointestinal protectivc absorption tests in coeliac disease, but are the major 'Fe-binding peaIk in adults wxas a effects of henzodiazepines (H3Z) in vivo are not ideal for screening as the sugars arc high molecul'ar weight (MW>¢45000() poss- generally assumed to reflect a central often difficult to analyse and chromato- ibly ferritin) accounting for 62%S ot eluted action. We examined the influeLIce of graphy is usually required. We describe a counts. The differences in iron binding several BZ on duodenal HCo) secretion, a chemical technique for analysis of lactulose proteins and iron uptake along the villus process which protccts the tissue f'rom and compare the lactulose/mannitol might aiccount tor the difference bctween luminal H byt generating a standing pH (La/Ma) test to a standard cellobiose/ neonatial and adult iron absorption des- gradicnt at the mucosal surface. Bull frog mannitol (Ce/Ma) test in two groups: (1) cribed in vivo. Similar studies in haemo- proximal duodenum wats stripped of sero- newly presenting coeliacs (17); (2) healthy chromatosis might shed light on its patho- muscle layers, mountcd in a chamber and controls (12). The test solution comprises geniesis. alkalinisation of the unbiuffered luminal 5 g lactulose, 2 g mannitol, and 22-3 g bathing solution mea;sured by conitinuous glucose in 1)() ml water (hyperosmolality titration at pH 74 dilazeparm (1-01()( !M enhances discrimination between coeliacs serosill side) induced a dose-dependenit rise and normals). This is ingested after a six Localisation of VIP binding sites in human in luminall alkalinisation and transepithelial hour fast and urine collected for five hours. and guinea pig gut using in vitro autoradio- potential differenice (PD). Although somiie Lactulose is measured by an enzymatic graphy 50)0-times less potent thian prostaglandin E, method anid mannitol by spectrophoto- the increase in secretory rate was compar- metry, the result being expressed as a ratio R F POWIER, A F' BISHOP, M A (GIIAT I, S R BOOM, able to the PG-induced tissue miaximia. which eliminates extraneous factors (gastric ANI) J M P0l1AK (Departmnent.s of' Histo- Pretreatment with indomethacin ( I IM) and bladder emptying, etc). The median cheinistrv and Medicinie, RPMS, Hatmmer- had no eftect whereas 2,4-dinitrophecrol La/Ma test was )-08() (range 0)-)2-1-356) in smith Hospital, London) Despite numerous abolished the response to broth agonists. coeliacs and 0(016 (range 0004-( (028) in studies of peptide receptors by binding Dose-related stimulation of alkaline secre- controls (p<()-()0l) as compared with a techniques on isolated membrane preparai- tion and PD was aIlso observed with chlor- median of )- 112 in cocliacs (range 0-024- tions, little information is available on their diazcpoxidc, nitrazcparm, flunitrazepamn 0-720) and 0)-1 in controls (range 0-008- precise localisation. In this study, we have and beta-ciarboline which increaised secre- 0-024) for the Ce/Ma test (p<0-00l). There used the tcchnique of in vitro autoradio- tion by,70%, 60%, 90%, aind 55") respect- is no significant difference between the two graphy to localise receptors for vasoactive ively (aIll n=4) of the PGE, maximal tests. This method fulfils the criteria for an intestinatl peptide (VIP), one of the most response. These data show that BZ cian aict ideal screening test, it is of low cost, simple abundant peptides present in the enteric locally to stimulate electrogenic, energy to do and analyse, and is non-invasive. It nervous system, in humain and guinea pig dependent duodenal HCO( secretion by a compares favourably with the Ce/Ma test small rind lairge intcstine, where it is known mechanism which is indepeindent of ciildo- http://gut.bmj.com/ which is highly sensitive and moderately to have potent aictions. Unfixed cryostiat genous PG production. speclfic. sections werc incubated with radiolabclled ('"I) ligand at a concentration of I nM. Specificity ot binding was confirmed by incubation of further sections with radio- Preparation of osmotically active brush Developmental changes in the villous uptake labelled ligand and unlabelled VIP at a border membrane vesicles from biopsy or iron and enterocyte iron binding proteins concentration of I uM. Autoradiograms samples of human small intestine in the guinea pig duodenum were generaited by exposure of the sections to LKB-Ultrofilm or emulsion coated glass S P SHIRAZI-B1i.ECIIFY, A G DAVIES, ANI) R B on September 26, 2021 by guest. Protected copyright. S K S SRAI, E DI.BNAM, ANI) 0 EPSTEIN (Royal coverslips. Arcas of dense binding could be BHIEt liii.Y (introduced by R M (ASE) (Dept of Free Hospital Sclool of' Medicinie, Lonidonl) identified, correlating with the known Biochemistrv, Universits' College of Wales, In ai previous int vivo study we showed that actions of the peptide. For cxampre, bind- Aberv.stwvtth, Dvfied, atidl Brontgl(at.s the rate of iron uptake by neonatal guinea ing sites appe(ared to be dense in the smooth Hospital, A bervystwyvt/, Dyied) The strategy pig duodenum is substantially higher than muscic and mucosa, in keeping with the has been to prepare aind characterise in that of adults. We proposed that the failure pcptidc's effects as a muscle relaxant and detail the brush border vesiclcs from differ- of postnatal adaptation in man might be a stimulator of watcr and electrolyte secre- ent regions of the rabbit gut. This has been factor in the pathogenesis of haemochroma- tion. The methods described here open new performed on a large scale. Brush border tosis. This study reports the use of auto- opportunities for study of the anatomical vesicles were thenl prepared from hiopsy radiography to define changes in villous distribution of peptide binding sites in the sized portions of the rabbit gut. The proper- localisation of iron uptake and gel filtration gut. They may be particularly useful in tics of these vesicles were compared with of enterocyte soluble supernatant (SSN) to defining the pathogencsis of certain those prepared on the large scale. No major study the ontogeny of iron binding proteins diseases. differences were noted. in the guinea pig duodenum. We have used the technilques that were Autoradiography revealed that whilst all developed with rabbit tissue, to prepare neonatal enterocytes took up "Fe, only brush border vesicles from human jejunum those in the top half of adult villi take up the Benzodiazepines stimulate duodenal and duodenum biopsy material. These isotope. epithelial bicarbonate secretion vesicles have a characteristically high level Gel filtration of SSN on Sepharose 6B o alminopeptidase N. They also havc a Na'.- indicate that in the newborn guinea pig the J R IIHIYLINGS, S E IIAMPSON. ANI) A (ARNi.R dependent D-glucosc transport systcm miajor "Fe-binding peak has a low molecu- (Bioscience D)ept, ICI P/harmnaceuticals located within their membrane. This has a Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from
A 1 334 The British Society ofG(lastroenlterology' very high activity, 1 6-3-4 nmol 1)-glucosc w,atcr and solute transport in infatnt mouse induced damage, which involved 3()+4 YO transported/milin mg protein. Thc transport intestine, using "4C-polyethylene glycol as a (n=6) of the total mucosal area was reduced is inhibited by phlorizin. The time course non-absorbablc water marker. Control (p<0-05) by BW755C at doses of 20) mg/kg for the Na '-depcndent uptake of D-glucose small intestinc, perfused with WHO oral anid St) mg/kg (42±13%) and 63± 12%. by thcsc brush-bordcr vesicles shows a rehydration solution (Na 90 mM, K 20 mM, inhibition respectively), as was the mucosal transieint accuniuliltion, that is, typicil over- HCO) 30( mM) with glucose replaced with formation of LTBI (79+4%O and 78±7 shoot behaviour. Ihc level of accumulation mcannitol, cxhibited a mean (SEM; n) inhibition respectively, p<0-0l) and LTC 4 of D-glucosc shows that the trainsportcr in steady-state net water aibsorption over a (92+2 MO inhibition at 20 mg/kg, p The British Society ofGastroenterology A I1335 and bombesin, are released locally suggest- uptake which is known to be via a Na- between allografts and the other control ing possible mechanisms that may operate glucose cotransporter. It was found that groups stutdied, suggestillg vilIlLs absorptive to limit the extent of ischaemic damage. glucose uptakc was ( 1) stimulated 35-fold in functioni remains intaict. We concluide that the presence of 10)() mM Na compared with the rectioll of water absorption in K. (2) a further two-fold stimulaition occur- SuccCssfIul sm1a1ll bowel transpaiits is Electrophoretic analysis of microvillus red when a negative diffusion potential was prinarily caLused by denervation rather than membranes in coeliac disease created by substituting thiocyanate for rejection or ischaemnia. chloride and (3) varying the osmolality of the medium altered the equilibrium uptake P W PEMBER ION, R W l OBI LY, AND R 1101 MI.S Segmental variability of electrogenic Na+ (Unii'ersitvi Department of CaGastro- of glucosc. In contrast, no difference was enterologi', Manchester Roval Infirmary, found in acetate uptake (1 mM) in the transport in human colon Road, Manchester) We have pre- presence of Nai or K. Uptake viaried linearly O.Vfiord ( I SANi)IDE ANI) : MC(iLONF. of viously described a technique for analysing with time up to two hours and there was no (l)eparlteni evidence of saturation of uptake at higher Medicine, Hope Ho.spial (Universitv of microgram amounts of intestinal micro- Manchester School of' Medicine), villus membranes by two dimensional concentrations up to 10)0 mM. Uptake wats Sallford) enhanced at pH 5-5 compared with pH 7-4 Electrogenic Na' transport is present in electrophoresis (protein mapping) and used normal humran distal colon and is enhanced it to determine the protein composition of (672.5+65 v 438 7+23.1 pM/mg protcin. respectively; p<0t)*01). Acetate could not by aldosteronie. 'I'he Na' chalnnel blocker normal human membranes. We have now miloridc markedly inhihbits hasal electro- applied the tcchnique to the analysis of the creatc a negaitive diflusion potential for glucose uptakc. Vairying the osmolality did genic Na' trainsport in humain disital coloni membrane in coeliac disease. but has considerably less effect in huLimian Jejunial biopsies were obtained from con- alter acetate uptake at 90 min. These data lend no support for the presence olf a Na- proximal colon. To further study the baisis trols, and from coeliac patients in rclapse for this segmental difterence in amiloride and remission. Microvillus membranes acetate co-transporter but rather suggest non-ionic diffusion of unionised acetate, the sensitivity, the effects of aimiloride ( I) M) were isolated by the Ca` precipitation and Na' replaicenient with choline were method, solubilised in 20O SDS and radio- majority of which rcmains in the BBMV membrane in this system. determined in proximall (asccnding) and labelled with '4C by reductive methylation distal (sigmoid/proxim-al rectumiii) coloni before electrophoresis. One dimensional resected from patients with cancer or separation was performed by conventional diverticular disease. In NaCl Ringer, basal S[)S-polyacrylamide gel electrophoresis Denervation is the prime cause of reduced electricail properties of proxinial (n=9) and while two-dimensional analysis was by iso- water absorption in successful rat small distal colon (n=8) were simill.ar, aind the clectric focussing followed by SDS-PAGE. bowel transplants mucosal addition of' amiloride decreased Proteins wcre detected by fluorography of short circuit current (Isc) by 147+32 http://gut.bmj.com/ the dried gels and glycoproteins by lectin- A J M WATSON, I' A lEAR, E .1 IL.[II01-, R F M (p<()-t()5) and totatl conductani(ce affinity staining of Western blots. RA/cm' WOOD, AND M J G FARTHING (Depts ofCGastro- (G,) by 1(6±0(6 mS/cm' (p<().()5) in distal Compared with controls, the protein map enterology and Suirgery, St Bartholomew's colon, but only decreased Isc by 47+13 in untreated coeliac disease was grossly Hospital, London) We have previously jAA/cm' (p<)-01) aind G, by 1-2+0(4 abnormal. Numerous high Mr proteins, shown that in successful rat small bowel mS/cm' (p<()-05) in proxinial coloii. In including the brush border enzymes and transplants impaired water absorption can- choline Cl Ringer, Isc decreased allmost to other glycoproteins were absent, while not be accounted for by mucosal damage. zero in both colonic segments, suggesting smaller proteins - for example, actin, ,were To determine the cause of this reduction that electrogenic Nia' transport was present on September 26, 2021 by guest. Protected copyright. unaffccted. After treatment, the protein water absorption was studied in allografts equ,ally in the proximal aind distal colon. niap returned essentially to normal with (n= 1)) and compared with (1) Thiry-Vella Kinetic studies on the basolateral Na '-K' restoration of the high Mr proteins, and no (TV) loops (n= 1)), (2) isografts (n=6), pump revealed that the maximum pump specific abnormality of the coeliac micro- (3) denervated TV loops (n= 5), and (4) activity, pump affinity lor Nia', and the villus membrane could be identified. ischaemic TV loops (n=4) using a steady number of Nat' ions binding to each pump state perfusion technique of isotonic 30 mM site, were similar in the proximal and distal glucose-saline nine days after transplanta- segments. T'hus, short circuit current Acetate uptake in rat small intestine is not tion. All animals were treated with an throughout humain colon is Nat'-dcpeindenit sodium dependent identical dose of cyclosporin A (15 mg/kg and probably reflects in clectrogenic Nai for seven days only). Water absorption was transport proecss which is aimiloride- A J M WATSON, F A BRFNNAN, M J G FARTIIING, reduced by 55%, in allografts compared with sensitivc only in the distill segmenit. 'I'his ANI) P 1) FAIRCLIrOUG-H (Department of Castro- TV loop controls. This was not hecause of segmcntatl vairiability in aimiloride sensi- enterology, St Bartholomew's Hospital, rejection as there was a similar reduction in tivity miay reflcct a segmental differeiicc in London1) We have shown that acetate isografts (median 42-6, range (17 5-77-7) v mucosal responsivencss to aldosterone. stimulates sodium absorption in rat and allografts (median 39t), range (19.6-54-2) human small intestine. The aim of the dI/min/g, respectively). When TV loops present study was to establish whether Na- were denervated, however, water absorp- Differential effects of pure mineralocorti- acetate cotransport can account for this tion was reduced to levels found in allo- coid and glucocorticoid hormones on colonic effect. Acetate uptake was studied in brush grafts (median 26.0, range (8X7-48t)). Na+ and K+ transport border membrane vesicles (BBMV) which Water absorption was not reduced in were prepared using a Ca-precipitation ischaemic TV loops. In contrast, no differ- G I SANI)iDI AND F MC(i ONI (DeparIm'ni 0o technique and compared with glucose ence was found in glucose absorption Medicitne, Hope Hospital (OLi(iei of Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1336 The British Society ofGastroenterology Manchester School of Medicine), Salford) I( " M) partially antagonised phenol- mucosal defect in lung and jejunum in CD The glucocorticoid dexamethasone binds to phthalein whilst abolishing basal secretion allowing increased permeability. glucocorticoid and mineralocorticoid recep- (p<0.05, n=9), showing that cholinergic tors in mammalian colon, and stimulates and non-cholinergic secretory nerves may electrogenic Nat transport, K' secretion be involved. In the presence of atropine. Mucosal cell receptors and enteric nerves and mucosal Na',K'-ATPase activity, but it imitation of the cffects of phenolphthalein mediate the spasmogenic effects of bacterial is unclear which type of receptor is more by carbachol (I- xIO10 M) suggests that N-formyl oligopeptides on guinea pig ileum important in mediating these changes. We activation of neuronal cholinergic receptors therefore used microelectrodes in vitro to promotes the release of a non-cholinergic V S CHADWICK, C H IJOBSON, ANt) M F BROOM compare the effects of hyperaldosteronism secretory neurotransmitter. Apamin (Wellcome Medical Research Institute, (secondary to dietary Na' depletion) and a (5x " M), which had no effect on basal University of Otago Medical School, PO pure glucocorticoid (RU 28362, Roussel; secretory activity (p>)-05, n=9), com- Box 913, Dunedini, New Zealand) The 600(tg/10() g BW/day for three days) which pletely inhibited phenolphthalein (p<0(05, mechanism of the intestinal spasmogenic has no affinity for mineralocorticoid recep- n=8). As apamin has been reported to action of bacterial N-formyl (methionyl) tors, on Na- and K' transport in rat distal inhibit neural release of vasoactive intest- oligopeptides has not been defined. We have colon. Compared with control tissues, inal polypeptide (VIP), this suggests a role determined pA2 values for eight potential aldosterone increased transepithelial volt- for VIP as the non-cholinergic secretory antagonists (receptor, nerve or ganglion age five-fold (p<0)0)01), total conductance neurotransmitter. It is concluded that the blockers) of N-f-met-leu-phe (FMLP) using 2-3-fold (p<0(00 1), hyperpolarised the laxative action of phenolphthalein is parti- histamine, acetyl choline, nicotine, 5HT basolateral membrane by 11 mV (p<0(025), ally mediated by inhibition of small intest- and Substance P as control agonists. A and decreased the apical/basolateral mem- inal fluid absorption via a nervous pathway. synthetic FITC-labelled peptide and a brane resistance ratio by 64% (p<0.0l). In This appears to involve cholinergic activa- rhodamine labelled anti-FITC antibody contrast, RU 28362 increased transepithelial tion of a VIP-ergic nerve. were used to identify receptors for bacterial voltagc three-fold (p<0(001), had no effect peptides in ileal mucosa. on total conductance or basolateral mem- Atropine (pA2=8-4), pirenzepine (8X0) brane voltage, and decreased apical/ and tetrodotoxin (7-9) were potent antago- basolateral membrane resistance ratio by Lung permeability in inflammatory bowel nists of FMLP induced contraction suggest- and coeliac disease 60%X (p<0.01). Studies with specific ion disease (IBD) (CD) ing involvement of Ml cholinergic neural channel blockers indicated that both aldo- pathways which modulate slow excitatory sterone and RU 28362 induced appreciable D A F ROBERTSON, H SIDHU, N TAYLOR, post-synaptic potentials in the enteric A C L SMITH, AND G HOLDSTOCK Na' and K' conductances in the apical BRHTTEN, nervous system. Tachyphyllaxis experi- membrane. Kinetic studies of the baso- (Depts of Medicine anid Nuclear Medicine, ments demonstrated that 5HT and Sub- Southampton General Hospital, Souithamp- http://gut.bmj.com/ lateral Na'-K' pump revealed that aldo- stance P receptors were not involved. ton) Respiratory disease and subclinical sterone increased maximum pump activity Salazopyrine, known to block FMLP have been identi- by 230% (p<000l), but RU 28362 pulmonary abnormalities receptors on neutrophil leucocytes also fied as complications of both CD and IBD, decreased maximum pump activity by 45% antagonised FMLP responses (pA2=7-3). of the lung disease (p The BritisIh Societv of Gastroenterologyv A1337 p.g twice daily) or ranitidine (150 mg twice six weeks (829"% and 89X3(%). Patients who of Medicine, Dept of (liCnical Bactcriologi' daily). Demograiphic data wals evenly smoked were less likely to heal (p<0)-00 1). and1{ Histopathologv%, UMDS Gu(,'s and SI matched. The healing rates at four, eight. No significant difference wias detected in the Thoias' Hospitals, l ond(lonl) Fifty patients and 12 weeks were enprostil 60%O. 90%. and severity ot ulcer symptoms between the two (35 M, 15 F. meaitt age 39S5, raintge 20-60 940/ and for ranitidine 65%o, 90%o. and groups. Eight patients defaulted and eight yeairs) with NUIt) aind no recenit history of 1000(0o rcspectively. Diarrhoea was a were withdrawn because of adverse drug NSAID contisumptioni. were studied to common side effect of enprostil therapy effects, predominantly diarrhoea (five evaluate the effect of De-Nol on svymptomiis (25%). Maalox 'I'C, one ranitidine). Mlaalox TC is a and on infection with C p) 'lori(li.. All To assess the effectiveness of mainten- convenient antadcid formulation which is pattients had normal abdominal U/S and in ance enprostil therapy, half of the patients comparable in efficacy to ranitidine in the all gastroscopy revealed t10 significant were followed for one year without treat- healing of duodenal ulcer. G1 pathology. Patients were allocated ment, and the others were given enprostil 70) randomly to eight wceks treatment with [tg nightly. Endoscopy was done in both either placebo or De-Nol after which they groups atfter six and 12 months, or if ulcer Esaprazole increases gastric alkaline were re-evaluated clinically and enido- symptoms rcturned. The recurrence rate at secretion in man scopically. Antral biopsies were examined six and 12 months following ranitidine was bacteriologicailly and histologically. 670O and 750O and after enprostil 5t)00 and M (USiLANDI (Institlito di Medicinia Ititertia, Patients on platcebo aindi c-Nol did not 61%/ respectively. On maintenance enpro- Milatno, Ital') Esaprazolc, N-I(N- differ regarding sex, ige. smoking, alcohol stil, the recurrence rate was reduced to 30%o cyclohexyl-carbamoyl)methylI piperazine consumption and C pvloridiis +ve cultures aind 38%, respectively. Seven of 48 patients hydrochloride, is a novel antiulcer com- (1 1/25 in De-Nol and 8/25 in plaiccho stopped treatment because of diarrhoeai pound reportedly as effective as cimetidine group). All 19 C(P!loridiis +ve patients or abdominal cramps. So far, eight of 12 in the short term treatment of peptic ulcer. 100%') had active gastritis in contrast with patients have relapsed within six months of The drug, which has a low antisecretory only cight ( 193(%) of C p)ilorI(is -ve stopping maintenance treatment. activity, was found to exert cytoprotective patients (p<0)001 ). Dc-Nol eradicated C Enprostil is as effective as ranitidine in effects against various necrotising agents. In pyloridi. from 9 (81X .8o) Of the 11 +ve the healing of gastric ulceration, but at the order to further elucidate the mechanism of patients compatred with placcho which did 7t) Fg dosage, diarrhoea is a problem. action of esaprazole, the effect of the drug not eradicate C pvyloridi.s from any of the on gastric bicarbonate secretion has been eight +ve patients (p<0-01). In patients investigated in man. Twelve healthy volun- receiving De-Nol, compared with placcho. teers, 1i) men and two women, aged 18-56 the gastritis (p<0-01 ) and the symptoms A double blind randomised multicentre (p (CBS) on September 26, 2021 by guest. Protected copyright. pool) Patients with endoscopically confirmed increase (p<)-()l) in gastric HCO3 secre- tion, from 2-65±0-57 (mean±SD) to symptomatic duodenal ulcer were eligible A AIIMED1), S K CAIRNS, 1) VAIRA, ANI) P K for a double blind randomised multicentre 4-28±0-79 mmol/h was observed after SAL MON (Dept of (as.itroenterology', Middle- trial comparing the antacid, Maalox TC esaprazole treatment, this effect being sex Hospital, London) The role of cytopro- (three tablets one hour after meals and at detectable in all subjects. - tective prostaglandins (PG) in the patho- bedtime) with ranitidine (15t) mg twice Gastric HCO, ions are known to con- genesis of DU remains controversial, but tribute to mucosal daily). The randomisation was stratified protection by neutralis- leucotrienes ( LT) probatbly play a pro- according to smoking history. The sympto- ing back-diffusing H' ions within the mucus inflammatory role. We hatve measured the matic effects of treatment were recorded layer. Strengthening of the gastric mucus formation of immunoreactive PGE2 aind after one, two, and four weeks. Repeat bicarbonate barrier by esaprazole may LTC4 in mucosal biopsics taken from 13 endoscopy was done after four weeks when, partially account for the cytoprotective and patients with DU, both before and four if the ulcer was unhealed, treatment was ulcer-healing properties of this new thera- weeks after treatment with CBS. In all continued until a final endoscopy two weeks peutic agent. cxcept one, ulccr healed aftcr therapy. later. Multiple duodenal and antral biopsies Seventy nine patients were admitted to were incubated at 37°C in prewarmed/ the trial, 43 receiving Maalox and 36 raniti- Colloidal bismuth subcitrate (DE-NOL) in oxygcnaited (95%, 02+5/% CO,) Tyrode dine. No significant demographic differ- non-ulcer dyspepsia. Placebo controlled solution (basial release) and trainsferred to at ences were detectable between the two trial with particular reference to the role of second incubation contatining ionophonc groups. Thirty five patients taking Maalox Campylobacter pyloridis 5 !tg/ml A23187 (stimulated release). TC and 28 ranitidine completed the trial, Radioimmunoassay analysis of the super- the respective healing rates being similar at T ROKKAS, C PURSEY, N A SIMMONS. M I FIIIPE, natant showed basal synthesis of PGE2 was both four weeks (67.7%) and 73.30%) and at ANI) G 1. SILAI)EN (Gastroenterology Unit, Div significantly higher in antral thian duodenal Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from Al1338 The British Societv ofGastroenterologvJ mucosa (pg/mg WW/20 min, means±SEM) Sucralfate (SUC) v cimetidine (CIM) for the sucralfate on the intragastric pH (using a pH 1198±157-4 and 887+102-3 (p<0-02), treatment of duodenal ulcer (DU) associated microelectrode), on absorption of salicylate whereas release of LTC4 was significantly antral gastritis and on peptic activity. These parameters higher in duodenal than antral mucosa, were examined four hours after oral admin- 96± 18-1 and 56+12-2 (p<0-()1). lonophore W M iUI, S K lAM, J 110, C 1. IAI, A S F LOK, M M T istraution of test solutions. Sucralfate signifi- stimulated LTC4 generation was signific- NG, AND I.UI (DepartmenGits of Medicin]e cantly reduced the incidencc and severity of antly increased (duodenum 183 ±44-3, and Pathology, University of Hong Kong, mucosal erosions (p<0-00l) induced by p<0)1; antrum - 89+20-2, p<0-05), but Queeni Mary Hospital, Honzg Kong) Antral aspirin alone and when combined with the not the release of PGE, (duodenum - gastritis is closely associated with DU and thrce bile acids at both pHs of 1-5 and 6e5. 278±111-7 (p<0.01l); antrum 329±86-8 improves with DU healing and treatment Rats which received sucrailfate had a higher (p<0(OI) suggested a different cellular with misoprostol. We conducted a single (p<0)-00l) intragastric pH than those which origin for the two eicosanoids. Ulcer heal- blind, randomised study to comparc the did not receive this drug. Sucralfate did not ing after CBS therapy did not alter basal therapeutic effect of CIM, an acid inhibi- influence salicylate aibsorption or peptic PGE2 and LTC4 generation either in duo- tory agent (200 mg tds and 400 mg nocte) activity. Wc have shown that the protective denal or antral mucosa, but stimulated and SUC, aI site protectivc agent (1 g qid) on effcct of sucralfate against mucosal injury LTC4 formation was significantly reduced antral gastritis associated with active DU, induced by aspirin and bile acids is not pH (p<0-OOI). two atntral and two fundal gastric biopsics depcndent. The simultaneous use of drugs These results suggest that LT formation were taken during endoscopy beforc and which inhibit acid secrction, thus, may not may be of greater significance than PG after treatment. The activity of the gastritis reducc the protective efficacy of this drug. synthesis in duodenal ulcer disease. as assessed histologically by the infiltration Stimulation of alkaline production may play of polymorps was graded blindly by two a role but inhibition of pepsin and binding of pathologists as nil, mild, moderate or aspirin to sucralfate aire unlikely to bc severe. The two groups (CIM n=71, SUC factors in the mechanism of sucralfates n=69) were comparable in their clinicilI action. characteristics. Despite similar rattes of DU A single blind comparative study of miso- healing in the two groups (75(YO, 78% at four prostol to sucralfate and placebo in the weeks) the incidence of improvement of prevention of aspirin induced ulceration activity of antral gastritis (nil or mild as Effect of treatment with famotidine on endpont) was significantly higher in the T-lymphocyte populations and activity in F LANZA, K F" PEACE, 1. GUSTITUS, AND SUC (33-3%) than in the CIM (183%/) duodenal ulcer patients B DICKSON (Baylor College of Medicine, group (p<0-05) and in the healed DU group Houiston, Tv and C D Searle Skokie, II, R MOUNTFORI). A W PRI R JONES, E GROVI, the improvement was significantly higher in ECF'I, http://gut.bmj.com/ USA) We report for the first time, the the SUC (36-40/) than CIM (16-4%) group ANI) J C(OJTREI I (Universitv Department of' results of a direct comparison of the cyto- (p The British Society of Gastroenterology A13'39 sinilar to control values (13±+4(Xo non- Zluricl, Switzerland, Lilly--England) In our taken after supper ait 183(0 h. Statistical ulcer controls 12±50/). healthy controls previous studies H2-antagonists were more analysis to assess the hypothesis that 8+3% ) and did not vary significantly during effective after early evening intake than increasing doses would produce increatsilng treatment: three days - 13±6Oo; two weeks after late intake. The question arises suppression of' acidity was hy the non- - 13+6°/,, six weeks I l±5%. In conclusion whether the meal interacts with the drug. parametric PAGE test for order elects. famotidine does not modify T-lymphocyte We thus conducted a randomised double Median nocturinlul pH rose f'roni 13 populations or lymphokine production in blind placebo controlled crossover study. In (placebo) to 2-4 (92% decreiase ol icidity). duodenal ulcer patients. Immunomodula- each of 12 healthy volunteers six ambula- -(0 (99"/ decrease), aInd 6-7 (99% decreatse) tion by cimetidine may be due to molecular tory 24-h pH-metries (glass electrode in the with increasing doses of WY-45.727. Anti- rather than H-medilted effects. gastric corpus, 30) samples/minute, start at secretory effects during the day werc 4 pm) were performed. Drug serum concen- limited; 21 'o, 37%, and 75%0 decreases trations were determined in the first four respectively. Overall 24 hour median p11 hours. The following six treatments were rose from 1-3 (plaicebo) to 1-9, 3 1, and 4l5 24 hour and intragastric acidity plasma randomised: N6/D6 (nizatidine 300 mg at with 20 mg. 40 mg. aind 150 mg respectivelv. in volunteers gastrin concentration healthy 6 pm and dinner at 6 pm), N9/D6 (nizatidine Cleair dose dependenit decreasing acidity taking famotidine 40 mg nocte 30)0 mg at 9 pm and dinner at 6 pm), N6/D9, was confirmed (p<0-0001) and eflects were N9/D9, P/D6 (placebo, dinner at 6 pm) and greatest at night. Such potent suppressionl S liANZON-Mit LER, R E, P'OUNDER, S G BALI., D J P/D9, respectively. pH-medians were calcu- of gastric acidity should make WY-45,727 J AND A 0 JACKSON DAtG(iLrEISH, COWARD, lated from 6 pm to 12 pm (evening), from an effective ulcer therapeutic agent wortliv (Royal Free Hospital School of Medicine, 6 pm to 7 am (night) and from 7 am to 12 am of further study. London) Famotidine is a new H2-receptor (morning). This the effects antagonist. study compared In the evening period pH-values were on 24 h intragastric acidity and plasma higher with N6 than with P (mean values of concentration of the 7th of Effect of intravenous BMY-25368-01 (BMY) gastrin day pH-medians: N6/D6 3-5 v P/D6 1-4; N6/D9 treatment 40 mg or and ranitidine (R) on meal stimulated gastric with either famotidine 3-9 v P/D9 1-6); N9 was not different from placebo, taken as a tablet at 2100 h. The acid secretion in man P; N9/D6 was inferior to NO (N9/D6 1-7 v treatment was given in a predetermined N6/D9 3-9 and N6/D6 3-5). During the night It G DAMMANN, F BURKiiARD)i, P MUiIiF-R, B random order. Ten healthy volunteers took N6 and N9 were superior to P (NO/DO 3-8 part in the median age 22 years, SIMON, R R (CR.NSIIAW, K MANGiHANI, ANt) S 1 study: and N9/D6 3-6 v P/DO 1-9; N6/D9 3-3 and median weight 72 kg. SCIiWARJ/. (Kranikenthai.s Bellathiaen, Halm- N9/D9 3-5 v P/D9 1-5) (p<0-(0 multiple Median 24 h intragastric FRG, a1/1(1 Pharmaceutical Research integrated comparisons by Wilcoxon/Wilcox). The blurg, acidity fell from 066 pmol/h/l on placebo to effect of nizatidine ceased with breakfast. and Dev'elopmnent Division, Bristol-Mver.s 281 on 40 mg nocte. C(o, USA) In this blinded http://gut.bmj.com/ pmol/h/l famotidine Drug serum concentration peaked l120) Wallingf.ord, Conversely, median integrated 24 h plasma (BMY doses v placeho), randomised, cross- minutes earlier when nizatidine was taken gastrin concentration rose from 248 to 394 without meal than when nizatidine and meal over study, a singie iv dose of BMY (1- treatment amino-2 pmol/h/l during with famotidine. were taken together. [3-(3-piperidinomethylphenoxy) Both of these changes are significant We conclude that (1) A concomitant meal propylaminol cyclobut- -cne-3,4-dionc hydrochloride), an inhercntly long acting (P<(d)0)). slows the absorption of nizatidine and may and novel histamine Analysis of the data by 'meal-related thus prolong its action. (2) Nizatidine is H,-receptor antago- intervals' shows that the decrease of intra- nist, 50 mg of R, or placcbo was adminis- most effective when given at 6 pm together gastric acidity during treatment with tered to healthy voluntecrs. BMY was with a meal. Supported by SNF 3.827.0.80 on September 26, 2021 by guest. Protected copyright. famotidine is due entirely to a decrease of and DFG Em 36/1-3. studied at 5, 12-5, and 25 mg. Subjects nocturnal acidity - daytime acidity is received either BMY and placebo or R and unaffected by the drug. Famotidine 40 mg placebo. Six subjects were in each group nocte causes a significant increase of plasma except the BMY-5 mg group that consisted gastrin concentration during the night, of five subjects. Medications were adminis- morning and afternoon, with no effect in the Dose dependent inhibition of twenty four tered at (07(00 hours, and uniform homo- evening. hour intragastric acidity by WY-45,727 a genised meals (standardised to pH 5) wcrc Famotidine 40) mg nocte causes a signifi- new potent H2-receptor antagonist administered at 0800(, 13 00, and 180(t) cant decrease of nocturnal acidity, with a hours. Volunteers receiving 25 mg of BMY longer lasting rise of plasma gastrin concen- H MERKI, 1. WITZEI., J NEWMANN, D KAUF- were administered a 4th meal at tIS t)0 hours tration. MANN, AND J ROEHMEL (INIRODUCLD BY R P of the subsequent day. Gastric acid secre- WAIT) (DRK Hospital, West Berlin, FRG) tion was determined using an automatic WY-45,727 (Wyeth Labs) is a new furan titrator that maintained the intragastric pH H2-receptor antagonist of greater potency at 5 for two hours after administration of Optimising the effect of nizatidine on gastric than ranitidine (3-lOX). We measured the each meal. No untoward clinical effects pH: early evening meal together with the effects of increasing doses of WY-45,727 (20 were observed with either BMY or R. drug is best mg, 5() mg, 150 mg) on 24 hour intragastric Intravenous BMY is more potent than acidity in 20 normal volunteers in random and longer acting than R. A single iv dosc of P DUROUX, P BAUERFEINI). C LMD)i, H R KOil/, order under double blind conditions. pH 25 mg of BMY produces significant inhibi- I) MARGAILITII, G, DORIA, A KARPF-, PP was measured continuously by intragastric tion of meal stimulated gastric acid secre- KEO0iANIE, ANt) A 1. BlUM (Gastroenterology glass electrodes and each volunteer under- tion for 24 hours. Intravenous BMY is a OD CHUV-Lausanntie anid Stadt.spital Triemli- went four identical studies. Medication was antisecretory agent. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1340 The British Society of Gastroeniterology Omeprazole improves antral gastritis associ- daily (low dose), 20 mg daily (standard and omeprazole 2(0 mg (p=0(12). After ated with duodenal ulcer (DU) dose) and RAN 150 mg bd. Forty six adjustment for an imbalaincc att entry in potential factors affecting healing including terms of more patients with larger ulcers in W M [HUL, S K LAM, J 110, I lUI, W Y LAU, F J clinical and endoscopic characteristics were the omeprazolc 2(0 mg group, both omepra- BRANICKI, C I. [AI, A S F lOK, AND M M T NG prospectively obtained and healing was zolc groups produced significantly higher (Departments of Medicine, Surgery and assessed by endoscopy at weekly intervals healing rates at four weeks compared with Pathology, University of Hong Kong, and for at least two weeks and up to four weeks ranitidine (omeprazole 2(1 mg v ranitidine Government of Surgical Unit, Queen Mary if DU remained unhealed. The cumulative p=)-()0(l, omeprazole 4(1 mg v ranitidine Hospital, Hong Kong) Antral gastritis healing rates per protocol analysis in the p<0(-()()(5). There wats a more pronounced occurs in close to 100%(" of patients with consecutive four weeks were 43%, 77o, improvement in ulcer symptoms during the active DU. Whether gastric acid secretion 94%, and 95% for OME 1) mg (n=83), first two weeks in the omeprazole groups. A plays a pathogenetic role in antral gastritis is 49%, 86%, 93%, and 96% for OME 20 mg significant difference was shown between unknown. We carried out a double blind (n=87) and 29%, 63%, 83%, and 93% for omeprazole 4(1 mg and ranitidine (p=( ()2). randomised trial comparing omeprazole RAN (n 84) respectively. (Life table All treatments were well tolerated and (OME) 10 mg OM, 20 mg OM and raniti- analysis OME 10 mg v RAN, p<0(03, OME there was no difference in the prevalence of dine (RAN) 150 mg bd in 270 patients with 2(0 v RAN p<0(002.) There was a trend adverse events between the three groups. active DU. Healing of the ulcer was towards more rapid symptoms relief with In conclusion, omeprazole 2(0 mg and 4(1 assessed weekly by endoscopy with at least OME, particularly nocturnal pain during mg om have been shown to be superior to two antral biopsies taken to assess the the first week. In the omeprazole treated ranitidine 15(1 mg bd in promoting healing activity and degree of chronic inflammation group (combined 10 and 20 mg) healing rate of gastric and prepyloric ulcers, and there histologically by the degree of polymorph is lower in the smoker than non-smoker was a better symptom relief with omepra- and mononuclear cell infiltration respect- (p<0-0008), early than late onset (symp- zole 4(1 mg. ively and graded blind by two pathologists toms before and after age 3(1 years respect- as nil, mild moderate and severe. The sex, ively, p<0.02), remission >5 v <5 months age and maximal acid output were compar- (p<0(05) and high acid v normal (p<0(05) able in the three groups. DU healing at two by life table analysis. We conclude OME 1() Effect of omeprazole on postprandial gastric weeks was 77%, 86%, and 63% respect- mg achieved similar healing rates as OME and duodenal pH in exocrine pancreatic ively, while that at four weeks was 95%, 20 mg and both resulted in significantly insufficiency 960%, and 93% respectively. The percent- better healing rates than RAN. Smoking, age of patients with improvement in the short remission period, early onset and high G MCIAUCHLAN, (i P ( REAN, AND K F L MCCOLI. activity of gastritis in the four consecutive acid secretion adversely affected healing. (Utniversity Department of Medicine, weeks were 9%, 40%, 51%, and 530% for Western Infirmary' and Gastrointestinal OME 1( mg (n=78), 14%, 42%, 49%, and Centre, Southern General Hospital, Glas- http://gut.bmj.com/ 53% for OME 20 mg (n=81) and 2%, 23%, gow) In exocrine pancreatic insufficiency 30%, and 33% for RAN (n=82), and life Omeprazole and ranitidine in the treatment duodenal acidity (pH<4) may inactivate table analysis: OME 10 mg v RAN and of benign gastric ulcer - an international residual endogenous enzymes and gastric OME 20 mg v RAN, p<0(0I. The degree multicentre study acidity destroy oral pancreatic supple- of chronic inflammation showed similar ments. The effect of omeprazole on gastric changes. Gastric acid and smoking did not A WALAN, J P BADER, M ClASSEN, C B H W and duodenal pH has been studied in six affect the improvement of gastritis. Thus LAMERS, D W PIPER, ANt) R RU FGERSSON patients with steatorrhoea caused by despite similar DU healing rates at four (Linkoping, Sweden; Creteil, France; chronic pancreatitis. Combined glass on September 26, 2021 by guest. Protected copyright. weeks, OME 10 or 20 mg daily is signific- Munich, FRG; Leiden, Netherlands; electrodes (Radiometer GK28(1C) were antly better than ranitidine 150 mg bd in Sydney, Australia; M(ilndal, Sweden) The positioned in the second part duodenum improving antral gastritis, suggesting that aims of this international multicentre study and body of stomach and 24 h ambulatory intense acid inhibition helps to improve the were to study the ulcer healing and toler- pH measured after seven days on omepra- antral gastritis. ability of four to eight weeks' treatment zole 4(0 mg/day, omeprazole 2(1 mg/day and with omeprazole 2(1 mg once daily (om), placebo given double blind in random order omeprazople 4(1 mg om and ranitidine 15(1 with two week washout periods. The drugs mg twice daily (bd) in patients with gastric were taken orally at (1800( h and the two Omeprazole (OME) v ranitidine (RAN) for and prepyloric ulcers. Forty five centres in three hours postprandial periods after the duodenal ulcer - weekly endoscopic assess- 13 countries contributed a total of 6(12 midday and evening meals were combined ment patients of whom 2(13 received omeprazole and analysed. 2(0 mg, 194 omeprazole 4(0 mg, and 2(15 The percentage of the postprandial W M HUI, S K LAM, W Y LAU, F J BRANICKI, C L raniti'dine. period that gastric pH was below 4 ranged lAI, A S F LOK, M M T NG, K P POON, AND PJ FOK At four weeks, 59%O of patients in the from 58%-1()()% on placebo; on omepra- (Departments of Medicine and Surgery, ranitidine group were healed compared zole 2(1 mg it was O%O in three patients and University of Hong Kong, and Government with 69%o of the omeprazole 2(0 mg group 42%., 68%, and 86%/O in remainder and on Surgical Unit, Queen Mary Hospital, Kong and 80% of the omeprazole 4(0 mg group. At omeprazole 4(0 mg it was (1% in five patients Kong) To investigate the DU healing eight weeks, the corresponding figures were and 76% in one. In the duodenum, the efficacy of two to four weeks' treatment of 850%, 89%, and 960O, respectively. The percentage postprandial time that pH was OME, 270 Chinese patients with endo- healing rates were significantly higher with below 4 on placebo was 000/ in three patients scopically active DU were randomised to a omeprazole 4(1 mg both at four and eight and 13%, 15%, and 26%Yo in others, on double blind controlled trial of OME 10 mg weeks compared with ranitidinc (p=)()()1) omeprazole 20 mg it was 0%/0 in five patients Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1 34 1 and 5% in one patient and on omeprazole BY L BARBARA) (Ninleteeni Italiaii gastro- in both groups. A lower healing rate was 40 mg was (% in five patients and 14% in eniterological departments) The aims of this observed in patients with larger ulcers and one patient. The two patients with the trial were to study the ulcer healing, relief of longer treatment with H, receptor antago- highest gastric and duodenal acidities were symptoms and the tolerability of four to nist prestudy. the most resistant to acid suppression with eight weeks' treatment with omeprazole 2(0 It is concluded that both omeprazole and omeprazole. mg om and ranitidine 15(0 mg bd in patients ranitidine treatment resulted in high healing In conclusion, some patients with with benign gastric ulcers (GU). rates after two and four weeks in patients exocrine pancreatic insufficiency appear Nineteen centres participated with a total unhealed after six weeks treatment with H. relatively resistant to acid suppression with of 84 patients randomised to omeprazole receptor antagonist. oral omeprazole and even 40 mg mane may treatment and 83 patients to ranitidine not maintain postprandial duodenal pH treatment. Four and three patients in each above 4. treatment group were found to have malig- What really happens during maintenance nant ulcers and were consequently excluded therapy of duodenal ulcer? from all analyses. Serum gastrin concentrations and gastric The healing rate was significantly endocrine cell population during longterm F J S BOYD, J G PENS'I'ON, I) A JOiiNSiONI, ANI) (p<0(05) higher on omeprazole (35% K G WORMSiEY (Department of TllTherapeutics, treatment with omeprazole in man 74o, and 96%/O) than on ranitidine (9%, Ninewells Hospital, Dltidee) Current main- 53%, and 85'S) after two, four and eight tenance trial protocols do not evaluate the W CREUT7FELDT, R LAMBERTS, AND G weeks, respectively. At entry a relatively incidence of DU recurrence, the propor- BRUNNER (Departmenti of Medicine, larger portion of the patients in the omepra- tions of symptomatic to asymptomatic University of GCittingen, FRG, and Depart- zole group had small ulcers (<10 mm). ulcers at the time of recurrence, nor the ment of Medicine, Medical School, When adjustment WaS made for this proportions of asymptomatic ulcers which Hanover, FRG) Twenty four patients with omeprazole was still found to be superior to subsequently reheal, remain unchanged or or chronic gastric oesophageal peptic ranitidine in the healing of GU at all points cause pain. ulceration including four with antrectomy of observation in the Intention to Treat We have endoscopically re-examined 34 resistant to 300 mg ranitidine daily and unfit analysis. Symptoms were rapidly relieved patients at monthly intervals for up to onc for operation were successfully treated with on both treatments. Relief of symptoms was year during maintenance treatment of 20-60 for DU omeprazole (o) mg daily 13-21 faster and more extensive in the omeprazole with ranitidine 15t) mg ait night. If a painlcss months. serum Fasting gastrin concentra- group compared with the ranitidine group. ulcer was detected treaitment and lollow up tions were monitored and multiple gastric Both treatments were well tolerated and remained unchanged. We stopped the study mucosal biopsies carried out during gastro- only few adverse events were reported. in patients whose ulcers were associated scopy every three to four months and fixed Omeprazole 20 mg om has been shown with pain. The mediain follow up was cight http://gut.bmj.com/ in Bouins's fluid. Oxyntic mucosa was superior to ranitidine 150 mg bd in the months 1- stained with Grimelius silver for (range 12). technique healing of benign gastric ulcers. The incidence of recurrent ulceration was ECL-cells, antral mucosa immunohisto- 34/, at six months and at logically for G- and D-cells and analyzed by 46%/ 12 months. morphometry. The ratio of asymptomatic to symptomatic Omeprazole versus ranitidine in duodenal ulcers at detection was 5:1. Average Gastrin concentrations increased signific- monthly probabilities for events of interest antly during the first 12 weeks of treatment ulcer patients unhealed after six weeks treat- ment with H2-receptor antagonists in asymptomatic ulcers were: rehealling from 103±+14 to 205±29 pg/ml; no further 33%; unchanged 61%'; and pain 6%. The increase was seen thereafter. Volume spontaneous rehealing rate of 33%, in on September 26, 2021 by guest. Protected copyright. density of G- and D-cells in the antral FRENCHI COOPERATIVE STUDY (INTRODUCED BY A COR I1OT) (CHRU de Lille, asymptomatic ulcers means that in a 12 mucosa did not significantly change. The France) month trial with endoscopy of asympto- volume density of argyrophil cells in the We studied 151 patients with endoscopic- ally proven duodenal ulcer (greater axis matic patients at six and 12 months, recur- oxyntic mucosa increased from 0-49± 1% to rence rates would be underestimated by 0.97+0.-1"/O except in patients with antrec- >5 mm) unhealed after at least six weeks of treatment with either cimetidine 47%, and 33% at six and 12 months respect- tomy (0-23+0-04) but did not reach the ively. In order to provide accurate values of patients with gastrinoma (1-3± 800 mg (61 patients) or ranitidine 3(M) informat- mg The was tion on the incidence of ulcer recurrence, 0-23'., n=7). No clusters of argyrophil cells (90 patients) daily. study per- current maintenancc trial protocols should were observed. formed double blind and patients were be modified. It is concluded that hyperplasia of oxyntic randomly allocated to either omeprazole 2(0 argyrophil cells is mediated by the hyper- mg om or ranitidine 150 mg bid. Endo- gastrinacmia in man and antral G- and D- scopies were done on day 15 and (if cell volume density does not change during unhealed) on day 29. Endoscopic healing Effects of 'mucosal protective' and anti- longterm omeprazole treatment. was defined as total reepithelialisation of secretory drugs on assimilation of food (all) the ulcer site(s). Before breaking the bound vitamin B12 code 26 (day 15) and 36 (day 29) patients Omeprazole 20 mg om and ranitidine 150 were excluded from the per protocol J I HANSI.IP, D GIDDEN, F, J S BOYD), N MARKS, mg bd in the healing of benign gastric ulcers analysis. AND K G WORMSILFY (Departmenit of Thera- - an Italian multicentre study Healing rates after two and four week's peutics, Ninewells Hospital, Dundee, and therapy were 48% and 80X% for omeprazole Gastrointestinal Clinic, Groote Schuuiir L BARBARA, A SAGGIORO, J OLSSON, M and 46% and 75% for ranitidine (NS). Hospital, Cape Town, S. Africa) Normal CISI ERNINO, ANI) M FRANCEiSCHI (INIROD)UCEI) Relief of ulcer related symptoms was rapid assimilation of food bound vitarmin B13X Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1342 The British Society ofGastroenterology appears to require adequate acid and pepsin bicarbonate secretion (mean+SE, n=6: (Gastroenterology Units, St James's atid secretion, in addition to intrinsic factor I mg/ml=593± 118 to 611 + 163: 10 mg/ml= University College Hospitals, Lon,don,) The secretion, by the stomach. Drugs which 453±114 to 412±86 [tmol/h). Nd YAG laser can significatntly reduce inhibit gastric secretion, or have non- These results suggest that stimulation of rebleeding and mortality rates in bleeding specific B12 binding activity (R-factor-like bicarbonate secretion by bismuth does not peptic ulcers, but less expensive electrode activity), or bind with B,2-intrinsic factor occur in man despite being demonstrable in systems might be equally effective. This complex may thus impair assimilation of vitro. study is a randomised comparison of the food-bound vitamin Bl,. We have studied best electrode (HP in our animal experi- the ability of a range of 'mucosal protective' ments) with the best laser (Nd YAG in our agents to bind with B12 or B12-intrinsic clinical trials) and no endoscopic therapy. factor complex in vitro, and the effects of a One hundred and forty three consecutive range of 'mucosal protective' agents and patients with a bleeding peptic ulcer and gastric antisecretory drugs on the assimila- F- NDOSC(OPY stigmata of recent haemorrhage (SRHI) tion of egg yolk bound vitamin B,2 in accessible to endoscopic therapy were patients undergoing treatment for duodenal Potential for endoscopic therapy in primary included. Stratification was according to the ulcer disease. sclerosing cholangitis type of SRH, and randomisation was bialsed De-Nol, sucralfate, carbenoxolone and towards the new therapy (HP). The diagno- antacid-alginate preparations bound either S R CAIRNS AND P B cOFrON (Department of sis of rebleeding and subsequent manage- vitamin B,2 or B,2-intrinsic factor complex Gastroenterology, The Middlesex Hospital, ment were by a clinician unawatre of the in vitro, but these preparations did not London) Over 36 months, 17 of 23 con- therapy given. The rebleeding rate was reduce the assimilation of egg yolk bound secutive patients diagnosed PSC received significantly lower in L (20%) than C (42%O) vitamin B,2. Both ranitidine 15t) mg and endoscopic therapy. Treatment was sphinc- (p<0-05), but in HP (28%) was not signific- cimetidine 400 mg administered 90 min terotomy (SPfi) alone in five, nasobiliary antly different from either of the other before the test meal, or ranitidine 300 mg drainage (NBD) four (two with SPH), intra- groups. There was no significant difference taken on the evening before the test meal biliary steroid infusion (I-BS) five, (three in mortality rate between the three groups significantly reduced the assimilation of with SPH), endoprosthesis (EP) 10 (five (L=2%, C=9%, and HP= I%O). Coin1- egg-yolk bound vitamin B,2. Vitamin B,2 with SPH). Balloon dilatations were per- bined analysis of these results with our malassimilation is a possible consequence of formed in four patients (three EP, one previous randomised Nd YAG laser trial longterm therapy with antisecretory drugs, I-BS). with identical protocol but only two way but not with 'mucosal protective' agents. Sphincterotomy alone produced a mean randomisation showed significantly fewer L fall of bilirubin (Bil) 320O, alkaline phos- than HP rebleeds ( 14%° v 28%, p<0(05) and phatase (ALP) 29%, over 1- 11 months deaths (2% v 10%. p<0(05). The results (mean six) follow-up. Nasobiliary drainage confirm Nd YAG laser but not heater probe http://gut.bmj.com/ Effect of bismuth subcitrate on gastric provided clinical and biochemical improve- efficacy, and the combined results show bicarbonate secretion in vitro and in man ment in all patients, follow up three to nine significantly superior results with the Nd months (mean six) with mean fall in Bil YAG laser than with the heater probe. C J SHIORROCK, J CRAMPION, L GIBBONS, AND 39%, ALP 36%. I-BS was attempted in five W D W REES (Hope Hospital, Salford) The patients, successful in four, with mean mode of action of colloidal bismuth in decrease in Bil 59%'O, ALP 32%, follow up healing peptic ulcers remains unclear. We 1-28 months (mean 16). Endoprosthesis Multipolar electrocoagulation (MPEC) in have examined the action of bismuth sub- placement succeeded in nine of 10 patients the treatment of ulcers with non-bleeding on September 26, 2021 by guest. Protected copyright. citrate on gastric bicarbonate secretion; an and lowered Bil concentrations (mean visible vessels (VV): a prospective, control- important component of mucosal defence. decrease 4t)%) and ALP (mean decrease led trial Addition of bismuth subcitrate (1() to 1t) 27%h) in eight patients with substantial M) to the luminal side isolated amphibian symptomatic improvement in six, follow up 1. IAINE (INIROI)UCID 13Y .I VAIIN/UIILA) mucosa, mounted in a Ussing chamber, 1-28 months (mean nine). (USC School oj Medicine, Lose A igeles, produced a dose dependant increase in Six of nine patients given EP remained CA, USA) This study assesses the efficacy ol bicarbonate secretion (1() hM: 0-19+±004 to well without recurrence of cholangitis with MPEC in reducing the morbidity ol ulcer's 0(23±0+05: I()- M: 0 17±0-4 to 0-24+0-04; stable LFF's up to one year after stent with visiblc vessels (VV). Patients with It) M: 0-28+0-05 to 0-47+0-06 ,mol/ extraction. upper G6 haemorrhage aind (a) blood trans- cm2/h. All means +SE, n=6 and p<0-05). These results suggest that endoscopic fusions of -2 units in 12 hours: (b) systolic Using a previously published perfusion therapy may be useful, at least in the short BP s9() mm Hg, heart rate -11( beats/ technique the effect of bismuth subcitrate term, providing biochemical and clinical min, or orthostatic chainges in systolic BP (1-10 mg/ml) on human gastric bicarbonate improvement in most patients with sympto- -2() or heart rate :2(); or (c) hacmatocrit secretion was studied. Bicarbonate secre- matic PSC. drop -6%M in 12 hours were considered lor tion was calculated from the pH and pCo2 of entry (n=466). Patients werc ralndolised gastric aspirates while acid secretion was to MPEC or sham MPEC if endoscopy suppressed by intravenous ranitidine. After Randomised comparison of Nd YAG laser showed a VV in an ulcer without active a basal hour, bismuth subcitrate (1-10 (L), heater probe (HP) and no endoscopic bleeding (n=60). The patient and his mg/ml) was added to the perfusate and therapy (C) for bleeding peptic ulcer physicians were blinded regiarding treat- bicarbonate secretion measured for a ment. further hour. At concentrations within the K MA1-I1EWSON, C P SWAIN, M BLAND, J S The treatment and control groups haid therapeutic range, bismuth did not increase KIRKHAM, S G BOWN, ANI) r C NORTHFIEILD no significant differences in any ot 21 Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The Britisi Society of Gastroenterology A 1 343 characteristics evaluated at the time of was performed. Primary anastomosis randomisation. Results after entry for sham COLORECTAI- was achieved in only 47"%, however. MPEC v MPEC: rebleeding: 12/29 (410%) v Laparotomy findings were often at variance 6/31 (19%o); blood transfused: 3-0±0+7 v Acute septi iccomplications of diverticular with the pre-operative assessment. Wound 1.7±0.4 units; emergency surgery: 8/29 disease. A radical approach improves sepsis developed in 27.6%0 of cases, post- (28%) v 3/31 (10%); hospital days: 5-9+07 survval operative abscess in 15 patients, anasto- v 4-3±0+4; and cost: $5270+680 v $3780+ motic dehiscence in 12 8%Yo and stomal com- 480. Although these results appear to A P CORDERR, J WILLIAMS (INIRODUCED BY plications in 17.5%. Of the 105 pathological favour MPEC therapy. the differences are PROFESSOR TAYLOR) (University Surgical specimens available, pathology in addition not statistically significant. One death Uniet F Lev'el, Centre Block, Southampton to CDD was recorded in 19 cases including occurred in the MPEC group (without Ceneral Flospital, Southampton, and inflammatory bowel disease (four), and rebleeding); no patient died in the control Ipswich aHGospital, Ipswich, Suffolk) One carcinoma (one). There were 19 deaths in group. hundred and two patients with a final diag- series but only nine were caused primarily This interval report of an ongoing trial is nosis of. c mplicated diverticular disease by CDD. Faecal peritonitis carried the encouraging with regard to the use of undergoing urgent laparotomy because of gravest prognosis (57% mortality rate). The MPEC in ulcers with non-bleeding VV. A suspected peritonitis (n=81) or intra- audit has to date identified the necessity for larger sample size will be required, how- abdominal abscess (n=21) were studied precise definition of the complication and ever, to establish statistical significance in retrospewtivvely. Sixty two patients had pern- pathology. The need for a larger study has favour of MPEC. tonitis whic-h was faecal in 16 cases. Forty been highlighted in order that recom- one per cernt of patients had macroscopic mendations may be made about optimum colonic pern forations, 33% intra-abdominal management for each complication. abscesses atrid 42%0 colonic masses. Thirty six patientss were treated by excision or Histology and cytology compared for the exteriorisatiion of the affected colon, 41 by diagnosis of neoplastic lesions detected at proximal colostomy and drainage and 25 by Is colectomy for severe idiopathic constipa- colonoscopy drainage or laparotomy alone. Although 21 tion a success? inpatient doleaths were distributed evenly J J r TATE, A hIERBERT, AND (G T ROYIE overthesetthree groups, marked differences M A KAMM, P R IHAWILEY, AND J E LENNARD- (INTRODUCED BY I IAYILOR) (University between th(e groups in age, antibiotic treat- JONES (St Mark's Hospital, City Road, Slurgical Unit and Departtnent of Pathology, ment and seeverity of pathology made direct London) The experience of colectomy Southanipton General Hospital, Southamp- comparisonis unhelpful. Therefore, using a carried out for severe idiopathic constipa- ton) Increasing use of fibreoptic endoscopy computer nmodel, the prognostic signific- tion in one hospital over the past 15 years is in the investigation of the large bowel allows ance of tre,atment group was investigated presented. http://gut.bmj.com/ biopsies to be obtained more often than along with I12 other features which included Patients with Hirschprung's disease, previously. The small size of endoscopic age, medicaal history, operative findings and megarectum or megacolon, and secondary biopsies, however, may be less than ideal antibiotic trreatment. A significant advant- causes of constipation were excluded. All 44 for histological diagnosis. We have com- age in surviival to discharge was found for patients were women and the mean age at pared cytology of colonoscopic biopsy those treateed by excision or exteriorisation operation was 34 years. The mean pre- specimens with histological analysis. when other factors were controlled for in operative stated bowel frequency was once Seventy two biopsy specimens were this way (p)<0(05). In the absence of con- per 4-7 weeks, and abdominal pain (present obtained at colonoscopy in 38 patients using trolled trialhls, this is the best evidence of an in 970Yo) and bloating were prominent on September 26, 2021 by guest. Protected copyright. a standard 2 mm diameter biopsy forceps. A advantage for a radical approach in the features. Eighty eight per cent used laxa- contact smear was made from the biopsy treatment cDf acute septic complications of tives preoperatively. All patients had a specimen onto a microscope slide, this diverticularrdisease. normal barium enema. Colonic transit was being fixed immediately. The same tissue prolonged in 33/34 patients. Thirteen of 20 sample was sent for routine histological (65%) had inappropriate puborectalis con- examination. National audit of complicated diverticular traction on EMG with straining, and 22/30 One sample submitted for histology. and disease (73%) were unable to expel a water filled four submitted for cytology were unsuitable balloon from the rectum in a test of simu- lor cvaluation. The final diagnosis was R G TUDOR ON BEtIALF OF 1 HE SURGICAL lated defecation. carcinoma in 15 samples, benign adenoma RESEARCII SOCIFTY 'COILON CLUB' (The Eleven patients had a caecorectal and 33 in 25 and normal mucosa in 32. The sensi- General JHospital, Steelhouse Lane, patients had an ileorectal anastomosis. tivity of cytology for carcinoma was 87%. Birminghanmn) Thirty six surgeons represent- Mean follow up was 4-0 years (range two 'I'he sensitivity of histology for malignancy ing 32 hosp)ital centres in the United King- months to nine years). Postoperatively, was the same. Both techniques were 100% dom have collaborated to prospectively two-thirds of patients were able to stop specific. When results of biopsy and document tthe morbidity and mortality of using laxatives but 19 patients had diarr- cytology were combined the sensitivity complicateod diverticular disease (CDD). hoea (>2/day) and this usually persisted. increased to 1t)00). Two hundr4ed patients have been recruited Pain persisted in 70(% of patients and Cytology of colonscopic biopsies may be with a mean age of 67-8 years; 129 were remained a major problem. In a third bloat- carried out simply and rapidly and is a useful women. Sixty six per cent presented with no ing and straining persisted. During follow adjunct to conventional histology. The need previous history of diverticular disease. up five patients developed bowel obstruc- to repeat biopsies of suspicious lesions is One hundrred and twelve patients were tion and in five constipation recurred. avoided, managed b)y surgery, and in 100 a resection Eleven patients underwent further surgery Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1344 The British Society of Gastroenterology because of incapacitating diarrhoea or per- quent occurrence of reflux in this disorder. the third postprandial epoch was 100 (40)- sistent constipation. Rising of intra-abdominal pressure norm- 284) mm Hg, IBS vl 33 (15-257), NC. Preoperative physiology studies did not ally produces an increase in lower oeso- This study differs from other work in that correlate with outcome. Colectomy usually phageal sphincter pressure through a pressures were measured in the unprepared relieves constipation in these patients but vagally mediated mechanism. This response sigmoid colon. Under these physiological pain and other symptoms often persist. was subnormal in 13 patients. Efferent conditions higher intraluminal pressures vagal function, assessed by the ratio of peak than previously described in normals, and acid output after insulin induced hypo- significantly higher postprandial colonic Faecal diversion in the management of glycaemia to maximal acid output after activity in IBS were recorded. Crohn's disease pentagastrin, was subnormal in seven of 23 patients. Cardiac vagal function, assessed M C WINSLEI, ti ANDREWS, J AlEXANDER- hy heart rate variability with deep respira- Screening for colorectal cancer - an analysis WIl.LIAMS, R N AllAN, AND) M R B KFIGIII Y tion, was abnormal in six of 23 patients. In of 132 tumours (General Hospital, Birmingham) The role IBS patients with oesophagitis abnormality of faecal diversion in the management of of these tests of vagal function occurred G PYE, K C BAtLILANTYNE, AND J D IHARDCASTLL Crohn's disease has been reviewed by retro- with a similar frequency to that previously (Department of Surgery, University spective analysis of 85 patients who have documented in oesophagitis unassociated Hospital, Nottingham) One hundred and had 95 defunctioning procedures. Fifty one with IBS but abnormal vagal function also thirty two patients have been diagnosed as patients had an elective resection with a occurred in patients free from oesophageal having colorectal cancer within the test and stoma to protect an anastomosis (n=38) or disease. Impaired vagal function is common control groups of a faecal occult blood for co-e .nt colitis (n=13). Forty four in IBS. This explains the frequent occur- screening study for colorectal cancer. In the may were screen patients .. elective diversion alone as the rence of reflux in this disorder and also test group there 42 detected primary treatment for proctocolitis (n=23) be important in the pathogenesis of IBS tumours (SDT) and 32 tumours in those or perianal disease (n=-l). Significant itself. who had refused screening. Ten tumours sustained remission was obtained in both presented symptomatically in patients who groups (D=31 (70%) p<0(0l, R&D=42 had had a negative test. In the control group 48 tumours have been diagnosed. (82%Yo) p<0*0)01, median follow up 28 (6-24 Increased segmental activity and intra- months). A significant number of patients Twenty four of 42 (57%) of SDT were luminal pressures in the sigmoid colon of no longer required steroid therapy post Dukes' stage A compared with 1 1/90 (l12% ) patients with the irritable bowel syndrome: a diversion (D= 14/16 p<0Ol1, R&D=21/30, of non-screen detected tumours (NSDT), new manometric technique p<0.01). There was a significant improve- (Xy-=30; p<0()-0l). One of 42 (2-3%) of ment in post operative serum indices SDT were associated with hepatic meta- (D=ESR p<0-05) R&D=Hb p<0-)1, J ROGERS, J J MISIEWICZ, AND M M HENRY stases compared with 23/90 (26%) of NSDT http://gut.bmj.com/ (Department of Gastroenterology and (X-= 10; p<0-01). Nine of 42 (21%) of SDT albumin and ESR p<0 05. Fifty eight Nutrition, Central Middlesex Hospital, patients have undergone or await restora- were pedunculated polyps treated just by London) The pathophysiology of the irrit- colonoscopic polypectomy compared with tion of intestinal continuity, proctocolec- able bowel syndrome (IBS) is controversial. tomy has been carried out in 31 and three 2/90 (2,2°%) of NSDT (x2=14; p<0-001). We studied seven IBS patients, mean age 51 have died. Disease relapse occurred in 16 of The mean size of SDT was 31 mm compared years (31-75) and seven normal controls the 29 patients with continuity restored. with 50 mm for NSDT (t=4 2; p<0(01). (NC) 37 years (22-55) with a new technique Faecal diversion used to facilitate or limit Eleven of 42 (26%/) of SDT were histologic- of intraluminal pressure recording in the on September 26, 2021 by guest. Protected copyright. resection, for steroid side effects, to avoid ally well differentiated compared with 7/69 unprepared true sigmoid colon, using a 4- or delay proctocolectomy and for perianal (10%) of NSDT (x2=4-9; p<0-05). Three of lumen water perfused tube system placed by disease. The high rate of remission pro- 42 (7%) of SDT were fixed compared with flexible sigmoidoscopy at 50, 40, 30, and 15 duced by diversion suggests a faecal factor 22/82 (27%) of NSDT (x2=67; p<0.0 1). cm from the anus. After a 30 minute basal has a role in the pathogenesis of Crohn's Although overall benefit from population a 1000 Kcal mixed meal was given disease. period screening must be judged by longterm mor- and measurements continued for a further tality, those patients with screen detected 100 minutes. The intubated colon was tumours have better prognostic factors. treated as a study segment (sum of all four Abnormal vagal function in the irritable channels) for analysis, using Activity Index bowel syndrome [AI=area under curve calculated elec- tronically in mm Hg/min] in 10 minute H L SMARI AND MICHAEI ATrKINSON (Depart- epochs. Additionally mean amplitudes ment of Surgery, University Hospital, (MA) per channel were analysed in 10 Nottingham) Oesophageal symptoms in minute epochs. Activity index was signific- I IVER POSTERS irritable bowel syndrome (IBS) arise from antly (0)-001 The British Society of Gastroetnterology A1345 Birmingham) Six of the first 92 patients lower in PBC's (mean 8±SD 5-6 ng/ml) Sulphation and desulphation in normal transplanted in Birmingham developed a compared with controls (16-9±5-9) human liver and primary biliary cirrhosis syndrome of fulminant liver failure with (p<0-00l). In PBC's there waIs nO corre- characteristic clinical and pathological lation with serum bilirubin, length of history S IQBAI., C KVIRS,v ANI) F. IllAS (Liver Unlil, features which are presented here. The or history of bone fractures. Levels three Qulee(n Elizahbethl Hospital, Edlgbaiston, typical clinical profile was of an initially months to 41/2 years after liver transplanta- Birminghalim) We haive examined the hypo- uneventful postoperative period followed tion in 10 patients (including cight in whom thesis that cholestasis in PBC is caused by by a sudden, rapid deterioration in graft pre-operative values were available) were impairment of' sulphaite ion trainsf'er. function resulting in graft failure. All six increased (454+ 19 2) compared with pre- Sulphation of bile sailts is importaint to patients died. The characteristic patho- transplant PBC's (p<0(001) and controls facilitaite their urinary excretion whereas logical changes were those of massive (p<() 1((). sulphation of sex steroids is important in haemorrhage and hepatocyte necrosis. We have confirmed that circulating creating inactive hormone. The activities of Initially these changes were confined to osteocalcin concentrations are significantly lithocholic acid (LC) and estronc (El) centrilobular areas hut later spread to decreased in PBC. After liver transplanta- sulphotransferase and sulphaitaisc in involve entire lobules throughout the liver. tion levels are supranormal, suggesting that normal livcr (n=7) and PBC (n= 13) werc Inflammatory changes within necrotic areas bone turnover is increased. This observa- examincd. Hepatocytc cytosol wa1s analysed were usually mild. The mode of presenta- tion lends support to the hypothesis thait for sulphotransferasc activity and homog- tion in our six patients resembles other hepatic osteodystrophy maiy he arrested or cnate, prepatred from the same liver, for previously reported cases of fulminant liver reversed by liver transplantation. sulphalt.!sc. failure after liver transplantation. The Sulphotransf'erase was significaintly lowcr mechanisms underlying this process are in PBC compared with controls for both LC poorly understood and a number of aetio- (2 63±2()7 v 6 50±3 65, p<0(005) and El logical factors including ischaemia, infec- (0(33±0+29 v 1-23±0+58, p<0.0005) (nmol tion and rejection have been proposed. Liver transplantation for fulminant hepatic product formed/mg mcan ± failure protein/h, SD). None of our cases had any clinical or (FHF) El-sulphatasc activity was not signiicantly pathological features to suggest ischaemia different from normal liver) 618±+2.65 v' or infection and the changes seen histologic- C VICKERS, J NEUBLRGER, J BUCKELS, P 4.37± 184). LC-sulphatase was not detect- ally did not resemble other well recognised MCMASTER, AN[) E ELIAS (Liver Un1it, able in the one normal and one PBC liver patterns of rejection. A similar picture of Queen Elizabeth Hospital, Edgbaston, studied. massive haemorrhagic necrosis has recently Birmingham) The role of transplantation in The results indicate FHF significant deprcssion been described, however, in an animal is uncertain. The transplant unit has of LC and EI sulphotransferase activity in mode of hyperacute (humoral-mediated) very little time to assess patient suitability PBC liver. This could causc an accumulation rejection. The possibility that massive for the procedure and only a short time of the hepatotoxic sccondary bilc acid, http://gut.bmj.com/ haemorrhagic necrosis after liver transplan- period exists during which irreversible lithocholic acid, within PBC livcr and tation represents a form of accelerated neurological complications may supervene. impair conversion of free active cholestaitic humoral rejection is therefore suggested. Thus, there is a very short interval to obtain oestrogens to their inactive state. a donor liver. Thirty three consecutivc patients (13 M), median age 28 (17-64) developed grade III/IV hepatic coma because of paracetamol overdose (17), viral Natural history of primary sclerosing Circulating osteocalcin as an index of bone hepatitis (nine) and other causes (seven). cholangitis (PSC) HLA antigens as predict- on September 26, 2021 by guest. Protected copyright. turnover in primary biliary cirrhosis (PBC) Urgent transplantation was considered in 12 ors of prognosis pre- and post-liver transplantation (36°%) patents (viral five, other seven). Progressive renal impairment was present M L WIl.KINSON, P T I)ONAI DSON, B C PORT- R G P WArsoN, D COUILiON, J A KANIS, P in nine. Our criteria for liver repiacement MANN, J KARANI, ANI) ROGER WIllIAMS MCMASTER, AND F, EI IAS (Liver Uniit, Queen was age <55 years, grade 4 hepatic coma for (Gastroenterology Unit, Guy's Campus, Elizabeth Hospital, Birmingham, Royal a minimum of 24 hours and deteriorating UMDS oj Guy's and St Thomas' Hosp and Hallamshire Hospital, Sheffield) Osteo- coagulation. Cases of deliberate paraceta- Liver Unit, King's College Hosp, London) porosis is a major complication of chronic mol overdose were excluded. Continuous Survival and natural history of PSC are cholestatic liver disease. Aetiology is not medical reassessment was made up to the poorly understood and prognostic variables established and attempts at treatment have time a donor liver became available, with a have not been established. We have pre- been disappointing. Primary biliary cirrho- median interval of 40 hours (range 1i)-54). viously confirmed a positive association of sis patients have reduced bone turnover Of seven patients transplanted five (71 (0O) HLA B8 and DR3 and a negative aissocia- (Hepatology 1987; 7: 137-42). In a previous survived. All of these patients are in good tion of B 12 with PSC and suggested a report, this was associated with reduced health with median follow up eight months negative association of DR4. To exatmine circulating concentrations of osteocalcin (6-20). Three patients died awaiting aI natural history, prognostic variables alnd (Ann Intern Med 1985; 103: 855-60)) a non- donor liver and two recovered. Of 21 (64% ) their relation to HLA antigens the HLA collagen bone protein produced principally patients not considered for transplantation profiles of 54 N. European PSC patients by osteoblasts. In this study osteocalcin was 1() (47%) survived, including 54") of para- undergoing prolonged follow up study were measured by radioimmunoassay in 32 cetamol overdoses. correlated with clinical, radiological and women with PBC (ages 31-62 years, mean The results indicate that hepatic replace- laboratory profiles and with prognosis. 48) and 52 controls (women aged 35-62 ment may improve survival in selected cases Investigations included yearly liver biopsy years, mean 48). Osteocalcin levels were of FHF. and ERCP. Poor prognosis (death or liver Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1346 The British Societv ofGastroeniterology' transpl.antation) was analysed hy life tables ence of bacteriuria in SS. Persistent D A F R013[R'i'SON, S 1i ZiIANG, (GUY, ANI) -and correlated with other variables by bacteriuria was found in seven PBC, with RAI P1H WRi(iG (I)epartments o0f Medicine multiviariate analysis. Median survival was the same organism in 4/7. No CLD patient anid Microbiology, Southampton Genieral ovcr 8'/2 years. Poor prognosis was not showed persistent bacteriuria with the same Hospital, Solthiamiptoni) Autoimmune predictcd by age, sex, CUC, autoanti- organism. chronic active hepatitis (AICAH) is of bodies, piecemeal necrosis, prothrombin This study does not support a unique unknown cause. High antimeaisles antibody time, serum albumin, alkaline phosphatase association between bacteriuria and PBC. titres in AICAH suggest a possible role for or immunoglobulin (Ig) concentrations. SjS6grens syndrome does not appear to be an this virus, which is capable of persistclet 111 A B8 and DR3 were, however, associ- important factor for increased susceptibility infection, in incomplete form, in the central ated with poor prognosis and there was to UTI. In both PBC and CLD bacteriuriai is nervous system in subacute sclerosiiig significiant linkage disequilibrium between more common in elderly women with panencephalitis, despite a very high anti- thcm compared with 63 laboratory controls. cirrhosis. body response to some mealsles virus (MV) IgM rise (19/45) was associated with HLA antigens. To investigate the possibility that A I B8 and/or DR3. Poor prognosis was also persistent incomplete measles virus infec- predicted by serum bilirubin, yGT aind AsT, Epidemiology ofantimitochondrial antibody tion occurs in AICAH we have measured by histological evidence of cholestasis or seropositivity and primary biliary cirrhosis complement fixing antibodies ((TF) cirrhosis and by ERC, pairticularly extra- in the west of Scotland together with Western blot analysis ot the hepatic appearances. antibody response to meaisles in 18 AICA ItI B M GOUi)IE, G MACFARItANE, P BOYILI., A D paitients (aiuto-antibody positive. bionps proven), 19 controls with liver disease and BURI, C R GILItiS, R N M MA(SWi-FN, ANI) G WAl KINSON (Departments Medicine ntid 16 other disease controls. Very high anti- No specific association between primary olj meiasles antibodies were shown in AICAH biliary cirrhosis and bacteriuria? Pathology, Westerni Insfirtnary, tanid Cancer Surveillance Uniit, Ruchill Hospital, (geometric mean CFT 1/512 control 1/32) Glasgow, Scotland) During the period but these were confined to the nucleocap- * FIOREANI, 11 MITCHISON, R FREEMAN, sid, cellulair antigens, and polymerase with M BASSIEND)INE, ANI) 0 JAMI.S (Departments oj 1965-1980 715 patients in the West of Scotland (a region with a population of absent responses to the glycoproteill. Medicinle antd Microbiology, University of' matrix and envelope. These findinigs. Newcastle Upon Tvnze) This study aimed to three million served by a single immuno- pathology laboratory) were found to be together with the demonstration of confirm the reported association between sequences from measles virus nucleocapsid bactcriuria and PBC, and to examine seropositive for antimitochondrial antibody (AMA) using an indirect immunofluoresc- genome in the lymphocytes of 12 of these whether this susceptibility is related to liver patients suggests that persistent MV inIfcc- disease or the 'dry gland' syndrome. ence technique. Case records have been reviewed in 647 (90%) and liver histology tion may play a role in the pathogenesis ot (1) Screening study: we examined over AICAH. The correlation between MV http://gut.bmj.com/ six months 403 midstream urine (MSU) examined in 373 (52%) of these cases. The number of patients satisfying predeterm- genes encoding viral proteins, ind inti- samples from 160 consecutive unselected bodies to the proteins will be described. PBC patients (147 F, 13 M), 140 chronic ined histological criteria for the diagnosis of liver disease (CLD) paitients (65 F, 75 M), primary biliary cirrhosis (PBC) was estab- 23 primalry Sjogrens syndrome (SS) patients lished for the group in whom liver biopsies (,all women). Significant bacteriuria (> 105 were available and the results extrapolated organisms/ml) was found in 11-2%0 PBC, to provide an estimate of the frequency of Combination chemotherapy in hydatid PBC in the total AMA-positive population. disease 12l1% CLD and 43/. SS patients (NS). on September 26, 2021 by guest. Protected copyright. The prevalence of bacteriuria was higher in Between 1971-1980 when there was high women (12.2%Y PBC and 184% CLD) than ascertainment of AMA-positive individuals D IAYILOR, ) 1. MORRIS, ANI) S RIC'IIARI)S men (0% PBC and 6-6'Yo CLD). Bacteriuria the incidence of AMA seropositivity was 19 (Departmetnt of Surgers', Universits' was relalted to age (p<()-05 in PBC) and was per million per year. The estimated incid- Hospital, Nottinlgtiham) Chemotherapy of commoner in cirrhotics (PBC Stage 1 5- 100; ence of PBC was 11-4-15-2 per million per Echinoccus remains a diflicult area. We Stage IV 18-1%. CLD; precirrhotic 45%0 year and estimated prevalence 69-5-92-7 have previously reported encouraging in cirrhotic 14-6%0). E Coli wais the common- per million. There was sub regional varia- vitro ainial and clinicil results with est isolate (74%/ PBC, 63% CLD). (2) tion in the incidence of AMA seropositivity albendazole and more recently haive shown Prospective study: urine specimens were with a predominance of cases in urban/ praziquaintel to be a very activc scolicidal tested monthly (at one, three, and five industrial areas. The possibility of spacc agent ini vitro. As these two compounds are months by MSU; two, four, and six months time clustering was investigated using a completely different (bcnzimidazole/ by Uricult Dip Slide) from 29 PBC patients modification of Knox's test. No case cluster- isoquinoline). their ultrastructural eftects - eight 'early', 13 'intermediate', eight 'late' ing was shown, the observed number of appear difterent and they do not share the - six CLD and eight SS (all subjects pairs close in time and space showing good same toxicity problems, we felt that com- women). The cumulative ratte of bacteriuria agreement with the expected number bination chemotherapy should be con- of six months was 25' in early, 31%/ in assuming no inter.action. sidered. Combinnation chemotherapy has intcrmediate, 50%) in late PBC v 33%/ in not previously been studied in hydatid Cl D, 62-5% in SS (NS). TIhe prevalence of disease. Live ovine protoscoleces (f bacteriuria was higher by dip slide than Defective measles virus (MV) antigen grtatinulosis') were maintained in in vitro MSU (positive dip slides checked by MSU expression causes persistent MV infection in culture and albendazole (A) 5t)0 ug/l anid/or showed 5/16 ((31 /0) lalse positives) and autoimmune chronic active hepatitis praziquantel (PZ) 5), 2)0, l) fIg/l wias accounted for the appatrent higher preval- (AICAH) added with suitable untreated controls. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroeniterology A1347 Viability was measured by microscopy/ Estimated perfusion was 0-87 ml/min/ml Haem arginate therapy for acute hepatic eosin exclusion at three to four day inter- liver age 24, 0-70 age 91. We conclude that porphyria vals. Whilst both agents were active alone, the age related decline in liver volume, combinations reliably achieved better blood flow and perfusion may be the major K E L MCCOiL, M R MOORE, A III.RRI(K, M .1 rcsults than either drug alone (A v A+PZ component in the liver leading to the faLll in BRODIE, AND A GOLD)BEIRG (Universit y 50, p<0)-02; PZ 50 v, PZ 50+A 500, clearance of many drugs in aged man. Departmenit of' Medicine, Westerni p<0).05). Subtherapeutic concentrations of Itnfirmary, Glasgowu) Thc acute hepattic por- praziquantel when given in combination phyrias are causcd by hereditary deficicn- had a significant additional effect on viability cies of individual enzymes in the pathway of (A v A+PZ 10, p<0(05). Combination haem biosynthesis. Consequently, there is chemotherapy may allow significant IgG3 in PBC: raised serum concentrations increased activity of the initial rate control- improvements in efficacy and the avoidance and increased synthesis by peripheral blood ling enzyme of haem synthesis dclta- of dose dependant toxicity problems. lymphocytes aminolaevulinic acid (ALA) synthase, over production of the haem precursors formed P BIRD, A FLOREANI, 11 MIICHISON, 0 JAMES, before the enzyme block and impaircd AND M BASSENDINE (Departments of hepatic mono-oxygenase activity rclalted to Medicine and Immuniology, University ofj inadequate hepatic haem synthesis for cyto- Liver volume, blood flow and perfusion fall Newcastle Upon Tyne) Primary biliary cirr- chrome P450 formation. We have studied in aging man - an explanation for altered hosis (PBC) is an autoimmune disorder the effect of a new haem preparation, haem drug metabolism in the elderly characterised by positive antimitochondrial arginate (3 mg/kg/24 h iv for three days) in antibodies (AMA) and other immuno- 20 attacks of acute porphyria in six patients. 11 WYNNi., 1. 1i COPE, E MUIC'H, M D RAWLINS, logical abnormalities - noteably raised The mean urinary excretion of the haem K W WOOD)FiOUSE ANI) 0 F W JAMES (Utniversity serum 1gM. We have previously confirmed precursor ALA pretreatment was 32(1 of Newcastle Upon Tynle) It has hitherto that the AMA is predominantly of immuno- [tmol/24 h (range 180-602) and this fell to been assumed that the decreased elim- globulin subclass IgG3. We have now within the normal range (0-40) in each case ination of oxidised drugs in old age in man examined the serum concentrations of IgG3 by the third day of theratpy (p<0(001). was because ofagc related decreased specific in 104 PBC patients (diagnosed on conven- Leucocyte ALA synthase activity was 120(1 activity of human microsomal mono- tional biochemical histological and clinical nmol ALA/g protein/h (range 530-1800) xygen1asessimilar to that found in rodents; grounds), from two separate areas (70 before therapy and fell to 489 (range 215- but recent studies have shown no decline in English and 34 Italian patients- histological 720) 24 h after the last infusion. Antipyrine the spccific activities of several drug meta- Stage I, n=27; II, n=14; III, n=28; IV, t'2 (an index of mono-oxygenase activity) bolising enzymes with age in primates or n=35). A marked rise in serum IgG3 was was 18-7 h (range 7-2-41) over the 48 h man. We hypothesised that reduced observed in both English (mean 615±63'% immediately before starting therapy and fell http://gut.bmj.com/ elimination in man might be because of serum standard) and Italian (578±96) to 8-7 h (range 4-12-4) during the first 48 h decrcased liver sizc, liver blood flow, and patients versus age and sex matched controls of treatment (p<0,- 1). liver perfusion with advanced age. We (mean 70±22) (p<0-001)). Raised IgG3 These results confirm that haem arginate examined liver volume by parallel longi- was similar in patients at all histological effectively corrects the biochemical mani- tudinal beta-scan ultrasounds, using the stages. There was, however, a significant festations of acute hepatic porphyria and is method of Carr; we calculated liver blood correlation between serum IgG3 level and superior to previously used therapics. The flow from indocyanine Green clearance AMA titre (p<0(01). demonstration that impaired hepatic mono- after iv injection of 0(5 mg/kg. Sixty six To examine the basis of this raised serum oxygenase activity can be corrected by on September 26, 2021 by guest. Protected copyright. healthy volunteers (34 women) age 24-91 IgG3 (increased synthesis or altered clear- giving haem arginate indicates that the years (20 age <40, 23 age 40-65, 23 age ance) peripheral blood lymphocytes from exogenous haem is being incorporated into 65+) were recruited from hospital staff and 19 PBC patients and 18 age and sex matched functionally active hepatic haeemoproteins. local social clubs. None had hepatic, renal, controls were cultured in vitro and the respiratory or cardiac disease assessed by immunoglobulin synthesised in the super- clinical history and cxamination. All had natant was measured by capture ELISA normal blood count, liver blood tests, none specific for total IgG, IgG3 and IgG3 Kappa Nutritional support in fulminant hepatic took medications. Correlations between and Lambda chains. Primary biliary cirr- failure: the safety of lipid solutions liver volume, blood flow and perfusion with hosis lymphocytes in culture spontaneously age were assessed by Kendall's rank synthesised a higher % IgG3/total IgG than AlASTAIR FORBES, CLAIRE WICKS, WIll1IAM correlation. controls (p<0(001). This correlated with MARSHiALL, PHILIP JOHINSON, PAUI. FORSEIY, Liver volume fell from 21-4±08- ml/kg their serum IgG3 (r=0-69, p<0-001) and AND ROGER WILLIAMS (King's College body wt age <40 to 19 3+0-7 age 4(1-65 and indicated that there is increased synthesis of Hospital and School of Mediciine antd 155+t)-4 age 65+ (p<0-001). Estimated this isotype by lymphocytes in PBC. No Dentistry, Denmark Hill, London) When volume was 1470 ml age 24, 945 ml age 91 evidence for clonally restricted synthesis of fulminant hepatic failure (FHF) is pro- (linear regression). Liver blood flow fell lgG3 by PBC lymphocytes was found on longed the necessary nutritional support is from 17 6 ml/min/kg body wt age <40 to analysis of the IgG3 Kappa/Lambda ratio. hampered by concomitant renal failure 15 4 age 40)-64, 11-4 age 65+ (p<0)001). Some viruses preferentially elicit IgG3 anti- (limiting possible volumes), by insulin Estimated flow was 1260 ml/min age 24; 655 viral responses; conceivably identification resistance, and by a theoretical need ml/min age 91 (linear regression). Liver of factors which trigger this increased syn- to avoid lipid solutions (risk of toxicity perfusion fell from 0(84 ml/min/ml liver age thesis of IgG3 in PBC may provide clues to from fat accumulation and by thrombo- <40) to 0(81 age 40)-64, 0(74 age 65+. the underlying pathogenesis of the disease. cytopenia). In the present study the Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1 348 The British Society ofGastroenterology magnitude of the risk of iv lipid adminis- cirrhotics with varices and that there is a time (PT) , 17s and/or PC <80x 109/I, but tration has been assessed by acute lipid dose effect which may be of importance in no correlation with BT has been made. In challenge, and by prolonged lipid infusion the management of patients following acute 100 cirrhotics PC, PT, partial prothrombin as part of a parenteral feeding regime. Nine variceal haemorrhage and for the longterm time (PTT), and BT in minutes (simplate 11 patients with FHF complicated by renal administration of portal hypotensive drugs. General Diagnostics) were studied. Forty failure and cerebral oedemra (from para- two had a BT ¢ 10. Bleeding time correlated cetamol intoxication in eight from hepatitis with PC, above and below IOOx 10)/I A in one were given 500 ml Intralipid 1(% Prospective randomised trial of endoscopic (Spearman's p<0-(001). Of 63 cirrhotics over four hours. The median basal tri- sclerotherapy (ES) and transhepatic emboli- withPC 80x10)9/1, 19(30%/0)hadaBT>l0I glyceride level was 0(7 mM (0-4-1-7), that sation (TE) in patients with severe cirrhosis and 10 (16%) had also a PT <17s. Of 37 at the end of infusion 12 0 (7-1-22-5), aind and acute variceal bleeding. Preliminary with a PC <8)x 109/1, 17 (380/.) had a within eight hours all had levels -2-0. There results normal BT and nine (14%) had also a PT were no complications and platelet counts ¢ 17s. Forty five cirrhotics had a PT ¢ 17s of were unaffected. Four patients with P BONNIERE, J F C(LOMBELi, A CORTO-Il, M whom 22 (53%) had a normal BT; 55 had anthropometric evidence of millnutrition IIIFNRY-AMAR, C 1. IiFRMINE, AND J C PARIS PT <17s of whom 22 (4(0%) had a BT >10. went on to receive TPN which included 500 (Hepato-Gastroenterology and Radiology Cirrhotics with BT _t1), had worse liver ml Intria lipid 2("0% daily, for 7, 1(1, 15, and 41 Departments, University of Lille II, Lille function, without correlation between BTI days respectively. No complications attri- ancd Biostatistics Department, Villejuif, and PT, PTT or PC, suggesting that factors butable to the fat content were observed, France) Seventy five Child's C bleeding other than thrombocytopenia prolong BT. liver function tests continued to improve, cirrhotic patients have been randomised to This is the first report of a statistical correla- aind serial triglyceride levels did not rise ES (n =25), TE (n= 25) or to a control group tion between PC and BT in cirrhosis. A PC above 1-5 mM. All four pattients made a full (C) (n =25). Initial patient's characteristics >80 X 109/1 and/or a PT < 17s, however, do recovery and it is concluded that lipid solu- did not differ within the three groups especi- not predict a normal BT and vice versa. As tions may safely be incorporated into nutri- ally for clinical status and bleeding. plasma fraction iproducts do not correct tional support for patients with FHF. The mean time between admission and abnormal BT and platelets are not usually treatment was 8-3 h in ES patients, 8-2 h in given for PC ¢2(80x 109/l, an unrecognised TE patients, and 6-9 in C patients (NS). abnormal BT may remain uncorrected. Carbohydrate meals increase hepatic venous (1) A bleeding control was achieved in 25/25 pressure gradient (HVPG) in cirrhotics who (1()()%) ES patients, 18/25 (750%) TE have bled from oesophageal varices patients, and 19/25 (76%o) C patients Metallothionein and copper in liver disease (p=0.02). (2) The mean number of blood with copper retention: a histopathological units required two days after randomisation http://gut.bmj.com/ P A MCCORMACK, M GRA-FFEO, R D)ICK, N study 18 MORREAILE, I) WAGSIAFF, A MADDiN, N was 0(76 in ES patients, in TE patients, and 2-4 in C An MCINIYRI., AND A K BURROUGHS (Royal Free patients (p=0-02). (3) early M E, ELMES, N J MAHY, J P C(LARKSON, AND) Hospital School of Medicine, London) rebleeding during hospital stay occured in B JASANI (Department oJ Pathology, Protein but not carbohydrate or fat feeding 3/24 (12%) ES patients, 1/16 (6%) TE University of Wales College of Medicine, causcs a marked rise in hepatic blood flow in patients, and 5/17 (29(%) C patients (NS). Heath Park, Cardiff) Histochemical studies normal subjects and protein also signitic- (4) Eight patients died (32%) in ES group, of copper and copper associated protein antly increases (HVPG) in cirrhotics. We 11 patients (44% ) in TE group, and 11 (CAP) correlate poorly with hepatic copper in examined the effects of a protein free meal patients (44%) C group during the same content in Wilson's disease (WD). By on September 26, 2021 by guest. Protected copyright. (19 g carbohydrate, 5 g fat and 120 Kcal per period (NS). examining immunoreactive metall- 100 ml) on HVPG in 16 cirrhotics (15 men: We conclude that (1) ES was better than lothionein (IMT) immunocytochemically median age 49 range 20)-56: alcoholic n= 10O, TE and usual medical treatments for stop- and Cull and CAP using rubeanic acid and cryptogenic n=5, aiutoimmune n=i) who ping active variceal bleeding; moreover, it orcein respectively in 120 diagnostic liver had bled from oesophageal varices. Eight significantly reduced blood requirements. biopsies we attempt to explain this discrep- received a 600 Kcal (500 ml) and eight a (2) Although lower in ES, early death rate ancy and investigate the diagnostic value of 30)0 Kcal (250) ml) meal. Pressures were was not significantly improved by ES or TE MT immunocytochemistry. measured before and at intervals of ten as compared with control group. In normal liver (n=25) Cull and CAP minutes for one hour after the meal. were absent and cytoplasmic IMT was Hepatic venous pressure gradient increased present in centrilobular hepatocytes. In pri- in all patients after 600 Kcal rising 29%o from Is bleeding time a useful test in cirrhotic mary biliary cirrhosis (n= 14) Cull and CAP 15-6±SD 5-1 mm Hg to 20-2±SD 6-2 mm patients? were often found in paraseptal hepatocytes Hg at 30 minutes (p<0.)l) and by 22% and IMT had a strong overall distribution. to 19 1+SD 6-0 mm Hg at 60 minutes D SPRENGERS, P (RECIIl, P A MCCORMICK, N Degenerate hepatocytes in piecemneal (p<0.0l). After 300 Kcal HVPG increased MCINTYRE, AND A K BURROUGHS (Royal Free necrosis were intensely IMT positive. In in 7/8 patients, mean HVPG increased from Hospital School of Medicine, London) chronic active hepatitis (n=25) with piece- 185±SD 7-7 mm Hg by 15% to 21-2±7-1 Bleeding time (BT), a good test for primary meal necrosis IMT positive cells were mm Hg at 30) min (NS) and by 6% to haemostasis, is not routinely done in cirr- prominent against pale IMT staining of 19-6+8-2 mm Hg at 60 minutes (NS). These hotics. Bleeding time and platelet count background hepatocytes in contrast with results suggest that despite the flow results (PC) correlate directly below lOOx 109/l in WD (n=5) where all hepatocytes were in normal subjects non-protein meals hypersplenic thrombocytopenia. Increased strongly IMT positive. In sclerosing significantly raise portal venous pressure in bleeding risk is estimated with prothrombin cholangitis (n=4) and nonspecific cirrhosis Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A1349 (n=47) with cholestasis CulI and CAP were marker of hepatocellular damage, was Hg; p<0'05). Maximal increases in PSG found but IMT had no consistent pattern. measured by radioimmunoassay in 26 occurred at a median time of 20 minutes We suggest that metallothionein bound serum samples from 22 patients with after the meal and were sustained for a copper (Cul) which is not demonstrated histologically proven, autoimmune chronic period of observation of up to one hour. histochemically is detected by MT immuno- active hepatitis (CAH) and compared with The EHBF after the 80 g protein meal cytochemistry. This explains the discrep- aspartate transaminase (AST) levels at increased by 56% from a fasting level of ancy described and will be helpful in various stages of the disease. All but one 1399±SD 207 to 2474±SD 215 ml minute. separating piecemeal necrosis caused by patient were on steroid therapy and 13 were Increases in EHBF occurred within 20 WD from other causes. also receiving azathioprine. In 17 of the 26 minutes of the meal and coincided with the paired results, GST was raised compared increases in PSG. with only six AST levels. In 11 samples, These studies indicate that in patients Mitochondrial aspartate aminotransferase an abnormal GST was associated with a with portal hypertension protein meals (mAST) as a marker for alcohol misuse in normal AST concentration. All AST levels cause significant changes in portal haemo- patients with liver disease and controls in patients with GST levels below 8 ng/l (two dynamics that are dose dependent and times upper limit of normal) were normal related to increases in hepatic blood flow. C G ALVEYN, J BERESFORD, F G BULI, AND and only once when this threshold value of RAILPH WRIGHT (University of Southampton, GST was exceeded was there a correlation Southampton) Eighty three patients (51 between GST and AST. Patients with histo- Is the reduced vascular tone in cirrhosis men and 32 women) were studied, 22 with logically active CAH demonstrated caused by 'desensitisation' to sympathetic alcoholic liver disease, 20 alcoholics with abnormal levels of both enzymes but many nervous activity? normal liver function tests, 26 with non- patients with chronic persistent hepatitis and little of activity still had alcoholic liver disease, 15 epileptics on evidence A J MACGILCHRIST, D J SUMNER, J L REID, AND anticonvulsants; and 64 normal volunteers abnormal GST levels. r J THOMSON (University Department (32 M and 32 F) before and after ethanol These data show that ongoing hepato- of Materia Medica, Stobhill Hospital, challenge (1.1 g/k daily for one week). cellular damage is occurring in patients Glasgow) Severe cirrhosis is associated with Alcohol consumption was assessed by traditionally considered in biochemical reduced peripheral vascular tone despite questionnaire. Blood samples were taken remission and may explain why many sympathetic overactivity. We have investi- for routine liver function tests (LFT's), patients with treated CAH progress to cirr- gated whether sympathetic desensitisation mean red cell volume (MCV), glutamyl hosis despite treatment. may explain this anomaly. We measured transpeptidase (yGT), and mAST by the blood pressure (BP) responses to steady method of Rej. the ratio of mAST to total state intravenous infusions of the sympath- AST (tAST) was calculated. etic noradrenaline and the Effect of high and low protein meals on agonist (NA) http://gut.bmj.com/ Significant differences were observed in portal haemodynamics in patients with cirr- non-sympathetic pressor agent angiotensin the mAST/tAST ratio, the highest levels in hosis and portal hypertension II (All) in 10 severe cirrhotics (Pugh's alcoholics currently drinking heavily Grade B or C, group 1), 10 milk cirrhotics (median mAST/tAST ratio 21.6%). Those (Pugh's A, group 2) and 20 healthy controls who were drinking moderately (<80 g/day) N H AFDHAL, P A MCCORMACK, M KEOGHAN, AND J F HEGARTY (Gastroenterology & Liver (group 3), matched for age and alcohol or had stopped drinking were significantly Unit, St Vincent's Hospital & University intake. Before the study, the severe lower (14.6% and 11 8% respectively). The College, Dublin) Although splanchnic cirrhotics had raised plasma NA and ratio was significantly lower (median lowered BP compared with controls. The blood flow increases after a meal in normal on September 26, 2021 by guest. Protected copyright. 9.45%) in patients with non-alcoholic liver subjects, the postprandial increases in dose of NA or All which raised BP by disease and significantly elevated in epilep- hepatic blood flow and its relationship to 20 mmHg (PD2,,) was calculated from tic patients on anticonvulsant treatment changes in portal pressure in patients with individual dose response curves. Figures are (median 15.2%). In normal subjects, there cirrhosis and portal hypertension have not mean±SD, comparison by one-way was no difference in the mAST/tAST ratio been extensively studied. In this present ANOVA after log transformation. after one week's alcohol challenge. study the portal pressure (PSG; wedged Group Group2 (roup3 v 3 When compared with the yGT and MCV venous minus free hepatic PD210NA(4g/kg/min) 0)13+1)±1)0 1)1)7+±01-)2 01X+I±)0 1)p<) 05 the mAST/tAST ratio was a better index of hepatic pressure PD211 AII (ngkg/min) 2)) 6±21 9 6 ±+44 6 1l+ 8 p<0) l)2 venous pressure) and estimated hepatic Thus there is reduced vascular responsive- current heavy alcohol consumption than calculated using Indo- either of these standard parameters. blood flow (EHBF), ness to both sympathetic and non- cyanine green clearance, was determined in sympathetic pressor agents in severe nine patients with cirrhosis and oesophageal cirrhosis. We conclude that sympathetic varices following a 20 g and 80 g isocaloric, desensitisation may indeed occur in these Glutathione S-transferase levels in auto- isovolumetric protein meal. patients, but is not the sole explanation for immune chronic active hepatitis After the 20 g protein meal PSG the loss of vascular tone. increased by 22% from 11-6±SD 6-3 mm P C HAYES, A J HUSSEY, J KEATING, I A D Hg to 14 2±6-6 mm Hg (Student's t, BOUCIJIER, R WILLIAMS, G J BECKETT, AND J D p A 1 350) The British Society ofGastroenterology Surgery, St Jamnes'Xs University Hospital, same laser. Maximum necrosis (7x4 cms) SMAILI POSII'ERS Leeds) Jaundiced patienits exhibit at number was (achieved with 15 W for 67ff secs down INI'ESTINE of abnormalities of lipid metabolisms. eLch fibre simultaneously. These lesions for folate catabolism - These may have important implications healed safely, mainly by regeneration, with An assay implications the RDA when they require nutritional support. little systemic upset. for Plasma triglyceride (Tg) turnover was Larger volumes could be treated using M G J M J M ANI) studied in patients with obstructive jaundice more fibre insertionsi. Thermally induced COURINEY, MCPARILIN, SCOII, * (G WI IR (Dept of Clinical Medicine, Si (OJ), hepatocellular jaundice (FICJ) and necrosis has a potential for treating liver James's Hospital and Trinity College, controls with normal liver function. Paitients tumours and healing is likely to occur in a of status received an intravenous bolus of 1-2- similar way to necrosis in normanl liver. This Dlublimi) The assessment folate by laboratory based criteria is inaccurate, glycerol after pliasmalt Tg concentration was possible new treatment for ultriasonically and invasive. No measure of confirmed to be in steady statc. The deciay defincd intrahepiatic neopliasms, should costly folaite utilisation in vivo or reliable folate balance curve of pliisma radiolabelled triglyceride carry a lower morbidity than chemo- studics exist. Using radioisotopes we have ilctivity was used to obtain the fractional therapy, partial hepatectomy or liver trans- catabolic raite (FCR) and total Tg turnover plantation. shown thiat cellulair folatte catabolism involvcs cleavage at the C9-N 1t) bond with (V). subsequent urinary excretion or para- Pliasma I g turnover was reduced almost EfTect of SMS 201-995 on the growth and and its 10-fold in patients with HWJ (1-9±0 7 aminobenzoylglutamrate (pABGlu) mg/kg/h) compaircd with cointrols ( 18()+ development of hepatic metastases acetylated derivative. We hiave developed a to estimnate these 2-2 mg/kg/h) or paitients with OJ (1933+3-7 method quantitatively I) M NOJI, S A JENKINS, S (iRIMI, J YAIES, D W latter two compounds, without the use olfa mg/kg/h). The ratios of plasmaiIag turnover/ concentration suggest that patirents with OJ [)AY, .I N BAXII.K, AND (i COOKI (Uniiversity radiolabel in 24 hour urine collections in have reduced plasma clearance capatcity but Departments of' Surgery, Pathology antd animails and man. The assay involves puri- Nuclear Medicine, Liverpool fication ion normal hepatic Tg secretion. Patients with Royval by exchange chromatography Hospital, As reticuloendothelial before diazotisation and gel HCJ have reductions in both hepatic Tg Liverpool) polyacrylamide secretion and plasmna clearance. system (RES) inhibitors promote tumour chromatography prior to analysis by high growth the present study was carried out to pressure chromatography (HPLIC). The results indicate that patients with liquid establish whether an RES stimulant, SMS Daily urinary excretion (~tg/day) of HCJ and OJ may haive impLired ability to clear artificial fat emulsions from the 201-995, had any effect on the growth and pABGlu in healthy women was 28-2+9-1 development of liver metastases. Hepatic (x±SD, n=58) and in healthy men was plasma. Patients with HCJ maty be at risk of developing hepaitic steiatosis during mctaistascs werc induced in Fisher rats by 64 6±28X4 (n=42). As PABGlu represents nutritional supplemenitations due to their intraportal injection of 4x 10( Walker cells. one half of the degraded folate molecule, reduced hepatic Tg secretion. An cxperimental group (n=20) received these results indicate a daily folate catabo- http://gut.bmj.com/ 2 Ftg SMS 201-995 sc bd commencing on lism of 56 sg for these women and 129 ,tg the day of inoculation. Control animals these men. (n=20) werc dosed similarly with isotonic These excretion derived values approxi- Interstitial hyperthermia - a new therapy salinc. All rats were killed three weeks later mate 15% and 30(% of the recommended for intrahepatic neoplasms and the extent of liver replacement by dietary allowance (RDA) of folate for tumour assessed. Hepatic and splenic RES women and men respectively, suggesting a A C STEGEIR, K MATIIIEWSON, S ( BoWN, AND CG activity was determined by the uptake of substantial overestimation in the RDA. ('I ARK (Nationatl Medical Laser Centre, "9Technetium sulphur colloid and the effects on September 26, 2021 by guest. Protected copyright. Department o' Siurgery, Univer.sity College, of SMS on Walker cell growth measured Loncdon, The Ravne lntstitlute, Lonidoni) A both inl vitro and ini vivo. SMS 201-995 Incorporating lipid into soup or main course low power laser coupled to a thin flexible significantly inhibited the growth and has different effects on gastric emptying and fibre, inserted directly into tissue (inter- development of hepatic metastases (p<)-()5 nutrient absorption stitial therapy) can deliver energy to the Mann Whitney U Test). Thus in two centre of solid organs with great precision animals there was no tumour and in a K M CUNNINGHAM AND N W REA[) (Sub-Depft and without damage to overlying tissue. further 12 solitary metastases (1-2 cm of Humnan Gastrointestinal Physiology, atid This produces local thermal damage which diameter) were present. In four rats treated Nuitritioni, Uniiversity of Sheffield, Sheffield) is predictable in nature and extent. with SMS 25% of the liver was replaced by Three studies were carried out in each of six In normal rats we established that the tumour. In contrast in control rats the volunteers to investigate how lipid, given at maximumil diameter of necrosis produced degrec of liver replacement by tumour different stages during the course of a meal, with a single interstitial fibre was 18 cm, varied between 60-90/0. SMS stimulated affects gastric emptying and postprandiill with I Watt ot power tor 600s from a ND- the growth of Walker cells ini vitro but had blood glucose levels. The meal consisted of YAG laser. (Below I W less necrosis no eftect ini vivo. RES activity was stimu- 300 ml low nutrient soup, followed 20 occurred; above 1.5 W severe charring and lated by SMS, this effect being particularly minutes later by a 300 g mashed potato. vapourisation occurred around the fibre marked in the liver (liver: blood "Tc-Sc Sixty grams margarine was incorporated tip.) Healing was by regeneration. with SMS 4-41 +0-45, controls 2-20±0(41 into either the soup or the mashed potato. minimal scarring within six weeks. p<0t)2, Mann-Whitney). These results Incorporation of fat into the soup delayed I arger volumes of necrosis were pro- clearly indicate that SMS 201-995 signific- gastric emptying of the mashed potato com- duced in normal canine liver using multiple antly inhibit the growth and development of pared with the fat free control meal (ti-= treatment sites with four fibres activated experimentally derived hepatic metastascs, 114+11 v 67±7 min; p<0.05) by increasing consecutively or simultianeously from the possibly through RES stimulation. the lag phase (31±7 v 2±1 min; p<0-05), Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1351 but not affecting the slope (0-9±0.1 v I) A KEILiYx, J A ARMIiSTiEAD). ANI) A WAI KI.R- ( I ) JC true positive 13/16 (senlsitivity 0-8±0Xl"/ /min). This was associated with a SMi rii (Quleen Elizabeth lospf)ital 81"/ A1352 The British Society ofGastroenterology Intensive dietary counselling in adolescents mine release but food specific IgE measure- coeliac patients suggests that CD and DH with cystic fibrosis ments were always negative as well as the are different manifestations of the same detection of jejunal IgE plasma cells. disease process. Patients with CD and IgA J WILLIAMS, D A HANDY, P H WELLER, AND I W Gastrointestinal permeability was invest- deposits in their skin may represent a BOOTH (Institute of Child Health, University igated by the ingestion of 65 ml water hitherto unrecognised subclinical form of of Birmingham and Birmingham Children's containing 5 g lactulose, as a marker of DH. Hospital, Birmingham) Increasing energy absorption of large molecules and 5 g intake in patients with CF has been shown mannitol as a marker of absorption of small to have variable results; failure is frequently molecules. Complete five hour urine collec- A specific small bowel enema appearance in associated with poor compliance. Twenty tions were made, volumes recorded and non-responsive coeliac disease eight adolescents with CF (9-18; mean: aliquot of each preserved for sugar analysis 13.7) were studied over one year to assess using gas chromatography. N MIKiE, U UDESHI, J FERRANDO, AND P the effects -of intensive dietary counsel- In 100 healthy subjects mean mannitol ASQUITiI (East Birmingham Hospital, ling upon nutritional status. They were excretion was 14.3%0 (SD+3.3) and mean Birminghain) In untreated coeliac disease randomly allocated to three groups: group lactulose excretion was 0(30(% (SD±+020). (CD) small bowel enema shows a reduction (A) controls; group (B) received counsel- In the seven food pseudo allergic patients in the number of jejunal folds, and an ling to improve dietary intake to >130% of the mean mannitol excretion was 16.0(% increase in the ileal folds, compared with RDI (expected weight for height) using (SD+5.4) and the mean lactulose excretion normal. A unique appearance, reversal of normal foods and simple supplements; was 1-06% (SD+±055). the normal 'ejunoileal fold pattern with group (C) received counselling and also an Oral ritiometan (150() mg daily for a week) atrophy ot the jejunum and 'jejunalisation' enteric coated pancreatic enzyme supple- was associated with clinical improvement. of the ileum is rarely found in longstanding ment instead of conventional supplements. This treatment resulted in a significant untreated CD. The groups were matched for age, sex, and increase of mannitol recovery (27-5o; We have prospectively looked for this Shwachman score. SD+6.6) and in a significant decrease of reversal pattern. It was not found in 400 Surprisingly, the only group which lactulose recovery (0 62%; SD±+047). patients with various non-coeliac gastro- showed a significant change in weight when We concluded that raised gut perme- intestinal diseases, nor in eight patients with compared with the other groups was group ability to large molecules, probablv related CD who had a good response to a gluten B (mean weight SDS change±standard to inflammation mediators release, may be free diet (GFD). There was a significant deviation: Gp (A) -0-143+0 214; Gp (B) involved in the pathogenesis of food pseudo reduction in the number of jejunal folds in +0-037+0-245; Gp (C) -0-131±0-176 allergy. These abnormalities respond to the five untreated CD and 10 non-responsive (p<0-001)). Although there was also an oral treatment with ritiometan. CD patients, and a significant increase in increase in weight velocity in this group ileal folds (p of Gastroenterology, Regional Hospital, on September 26, 2021 by guest. Protected copyright. Cork, Ireland) Two previous studies found cutaneous vasculitis, two associated colonic Effect of ritiometan on food pseudo allergy no IgA skin deposits in normal relatives of carcinomas and one histiocytic lymphoma. patients with dermatitis herpetiformis Reversal of the jejunoileal fold pattern specifically identifies those coeliacs with a C ANDRE, F ANDRE, AND L DESCOS (DH). We have studied a distinct subgroup (Laboratoire d'immunopathologie of relatives of patients with DH, namely non-responsive state, who are likely to Digestive INSERM Centre Hospitalier those with coeliac disease (CD). We have suffer major complications of CD. Lyon-Sud, Pierre-Benite, France) Digestive previously reported on 119 patients with and extra digestive symptoms caused by DH, 13 (1177%) of whom had 21 relatives food pseudo allergy are identical to those of with a clinical history suggestive of CD. We Bread is digested more slowly and incom- an anaphylactic reaction but are caused by have established a histological diagnosis in pletely if made from coarse flour non-specific mechanisms. Gut inflamma- seven of these and have studied skin IgA tion may be an important factor in food and HLA typing in this subgroup. All were L J O)ONNELL, P M FMMETI, AND K W HEATON pseudo allergy. Ritiometan (INN) reduced on gluten free diets. Two had IgA deposits (University Department of Medicine, Bristol eosinophil chemotactic leucotriene genera- in the skin and one of these had DH. Six Royal Infirmary, Bristol) To discover if tion and histamine release from mast cells; were HLA B8 positive, five were HLA Al flour particle size affects starch digestibility it reduced PAF synthesis and inhibited C3 positive and all five who had DR studies we gave 400 kcal breakfasts of wholemeal activation. Its effectiveness was therefore were DR3 positive. The six probands all had bread and cheese in random order to ileo- assessed in seven patients presenting IgA deposits in uninvolved skin and five of stomates and normal subjects. Ileostomy troubles after the consumption of tyramine the six were B8 positive, four were Al starch excretion was measured for eight rich or histamine releasing foods. In these positive and of three studied two were DR3 hours postprandially using amyloglucosi- patients prick tests to food were sometimes positive. The genetic homogenicitv and the dase, also blood glucose and plasma insulin positive and related to non-specific hista- presence of IgA in the skin in some of the for three hours. With bread made from Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A1353 coarsely milled flour, starch excretion patients with normal fat aibsorption had ('linical Medicine, ('linical Microbiology (mean+SD) was 42% greater than with similar diarrhoeal symptoms (p A1354 The British Society ofGastroetnterology teers (x558+3 1 ppm), patients with func- Effects of vitamin E deficiency on small was mildly abnormal. Muscle biopsy tional bowel disorders ( x6-6+4-4 ppm), intestinal transport function showed atrophy of type 11 fibres and muscle treated coeliac patients (x9-9+8-1 ppm) selenium was )-23 g/g dry weight (adult RR: and disease controls (x7-0±6-7 ppm). No M SATO, M (OSS-SAMPSON, D PR MULLIER, AND 0(6-0)97 g/g). Chest radiograph, ECG and significant difference was found between P J MiLl A (Institute ofChild Health, London) echocardogram were normal. Fifteen grams patients with untreated coeliac disease and The gastrointestinal mucosa is vulnerable to per day sodium selenite was added to HPN bacterial overgrowth (5x 14 7± 14() ppm). damage by lipid peroxidation. Vitamin E and no other changc was made. Within The percentage of patients with raised H. (E) is a powerful membrane bound anti- three days muscle pain had improved; she fasting levels in untreated coeliac disease oxidant present in high concentration in began to crawl again and by six weeks she (58-8%) was significantly higher than that in enterocytes. We have studied the effects of was walking normally. At three months. the other groups, except for the patients E deficiency on mucosal function. Twenty plasma selenium had risen to 0(53 [tmol/I with bacterial overgrowth (43-7%). In 14 days old malc Wistar rats were placed on a and RBC glutathione peroxidase was 15 It/g coeliac patients studied before and after diet either deficient in E or one to which E Hb. Although biochemical sclenium deple- gluten-free diet, fasting H, levels decreased (l10) mg/kg) had been added. Brush border tion occurs in adults and children on long from 26-6+18 to 11-6+1) ppm, becoming membrane vesicles of small intestine were term HPN, symptomatic deficiency is rare normal only in those patients with recovery prepared by a Ca " precipitation method and poorly understood. The dramatic of intestinal lesions. Our results show that and glucose and sodium uptake measured. response to selenium repletion alonc high fasting H, levels are a frequent feature NatK+ATPase, cAMP and cGMP were suggested that it caused the myopathy. of untreated coeliac disease and that the determined in mucosal homogenates. Na+ Selenium is widely availlble in food but return to normal of these levels is predictive stimulated glucose uptake was rapid with an children with severe malabsorption on HiPN of villous regrowth. 'overshoot' in both groups but after nine are particularly at risk from scleniutn months of E deficiency maximal glucose deficiency and parenteral supplementation uptake was significantly impaired (757± 116 should be routinely considered for thesc v 1152±324 pmol/h/mg protein; mean+ 1 children. SD; n=5; p<0-05). H+ stimulated Na Inhibition of starch absorption by dietary uptake was similarly reduced (380+±148 l fibre 743+ 181, p<0-02). In the absence of a Na+ or H' gradient uptake of glucose and Na' Intestinal pseudo-obstruction: is manometry O HAMBFRG, JJ RUMESSEN, AND E GUDMAND- was not affected by E deficiency. No signifi- helpful? HOYER (INTRODUCED BY P M CHRISIIANSEN) cant differences in the Na+K'ATPase D AND (Gentofte University Hospital, Dept activity or cyclic nucleotide concentrations KUMAR, 1) 1. WINGATI, N S WIll.lIAMS, II -I of Gastroenterology F, Copenhagen, were observed. These data show that intest- H IOMPSON (Surgical and Gastroinitestinal Using the H,-breath technic, the Science Research Unils, The Lonidoni Denmark) inal transport is disturbed in E deficiency http://gut.bmj.com/ effect of three dietary fibres on starch and suggest that this is because of an effect Hospital Medical College, Lonidoni) The absorption was examined in eight subjects. on apical membrane transporters rather diagnosis of a primary disorder of small They received the test meals in randomised than on passive permeability or the entero- bowel motility is difficult and frequently order: (a) bread made of 10) g wheat flour, cyte Na+ pump. We speculate that E missed on clinical and radiological examina- coii- (b) bread made of 10) g low gluten wheat deficiency may contribute to the malabsorp- tion. Manometric evaluation may help flour, bread (a) with either (c) wheat bran, tion seen in some states of malnutrition. firm the diagnosis and indicate a specific (d) beet-fibre or (e) pea fibre, and (f) the motor abnormality so that managcment fibres seperately (15 g each). The quantity may be rationalised. We have carried out on September 26, 2021 by guest. Protected copyright. of H, excreted in excess of that produced by small bowel manometry in 14 patients (age the fibres alone was calculated. Skeletal myopathy secondary to selenium 19-60 years) with a suspected primary dis- The percentage of malabsorbed starch deficiency order of gut motility and 30 control subjects were: (a) 8%/ (4-17), (b) ()% (0-6), (age 18-55 years). Small bowel manometry (c) 12,5% (5-22), (d) 12-5% (5-20), and D A KELtLY, A SHiENKIN, A COL, AND J A was done using an eight port perfused tube (e) 12% (5-27). Low gluten bread was WALKER-SMITHI (Queen Elizabeth Hospital assembly and a low compliancc Arndorfer malabsorbed, in small amounts, by only for Children, London, and Glasgow Royal pump. Manometric evaluation confirmed three subjects, p<0-05. The increase of Infirmary, Glasgow) A two year old girl the diagnosis in 12 of 14 patients (85'Yo), and starch reaching the colon when fibre was with microvillous atrophy was maintained thus eliminated a psychiatric disturbance. added was: (c) 800% (: 14-133) p<0(05, on longterm home parenteral nutrition Motor abnormalities included bursts of con- (d) 36% (11-180) p<001 and (e) 660o (HPN). She presented with severe myalgia tractions occurring every 20)-3t) minutes in (33-163) p<001. Orocaecal transit times and regression of walking skills. Investiga- five patients, abolition of motor complexes were: (a) 360 min (210-420), (c) 165 min tions: normal full blood count, electrolytes, in one, tachygastria (5-6/min) in one (120-300) p<001, (d) 240 min (90-360) liver function tests and transaminiases. (normal 3/min), fast duodenal contractions p<0-05 and (e) 270 min (90-300) p<0 05. Serum concentrations of vitamins A, E, and (16-18/min) in two patients (normal 9-11/ We conclude that the dietary fibres B12, folate, zinc and copper were normal. min), retrograde peristalsis in one and impaired starch absorption, and this may be Plasma selenium was very low at <0-05 mol/l absence of motor quiescence following a an important factor in the regulatory effects (reference range (RR) 0 -2-() mol/l); RBC Phase III front in three patients. None of of dietary fibres on bowel function. The glutathione peroxidase was undetectable at the control subjects showed any of these gluten moiety seems to possess inhibitory l/g Hb and plasma glutathione peroxidase abnormalities. In the other two patients, qualities to starch absorption. All three was 6/1 (RR 90-35/1). RBC enzymes showed based on normal manometry, it was pOss- fibres decreased orocaecal transit time. normal B,, B., B, status. Electromyogram ible to exclude a primary motility disorder. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 1 355 Intestinal manometry is thus an essential increases stomach to caecum transit time cytes. In six of nine patients with IPD and investigation for the diagnosis and manage- (SCTT). This study aimed to investigate the EcAbs (titres > 1:64) aberrant cxpression of ment of patients with suspected primary gut nature of substances exerting this delayed DR molecules was seen in crypt entero- motility disorders. transit. Twenty two rats (250-300 g) with cytes. It can bc suggested that by analogy ileal cannulae (20 cm proximal to the with a similar phenomenon detected in ileocaecal valve) and six rats with isolated glands from paticnts with classical auto- Ontogeny of small intestinal motor activity ileal Thiry-Vella loops (7 cm) cannulated immune diseases, DR +ve crypt enterocytes for external infusion were used. After an would be able to act as Ag presenting cells, W M BISSET, J B WArr, R P A RIVERS, AND 18 h starvation, test substances were infused bypassing macrophage requirement. In the P J Mll.A (Department of Child Health, into the ileum for 20 minutes (0-3 ml/h) other three patients with EcAbs (titres Institute of Child Health, WC], St Mary's before the rats were fed 5 ml beans by <1:8) a decreased reactivity was seeni in Hospital Medical School, London) In the gavage. The infusion continued for a further villous entcrocytes. In all nine patients preterm infant the characteristic patterns of 160 min. Excreted hydrogen was monitored numerous DR +vc cells were present in the small intestinal motor activity are poorly continuously to give an index of SCTT. lamina propria compared to controls. We developed. Using continuously perfused Delayed SCTT of the bean meal was postulate that aberrant MCH molecule multilumen nasojejunal catheters we have observed during infusion of a triglyceride expression in the small intestine might studied the development of such motor (corn oil, p<002), a free fatty acid (oleic reflect loss of tolerance to luminal antigen activity in 12 preterm infants (28-42 weeks acid p<0.02), detergents (AOT, SLES which could. lead to autoimmune diseasc. gestation). Fasting activity was studied p<0-02), a bile acid (deoxycholate longitudinally on 28 occasions and on 23 p<0.05), a polyunsaturated oil (borage, blood short occasions the motor response to enteral p<0.05) and the fat analogue sucrose poly- Portal and peripheral chain fatty acid concentrations after caecal feeds was measured. With increasing gesta- ester (p<005) when compared with control (SCFA) lactulose installation at surgery tional age a clearly defined maturation infusions. Triglyceride infusion (intralipid) of fasting motor activity was seen with directly into isolated ileal loops also delayed E W POMARE, S PETERS, A R increases in: average duodenal pressure SCTT (p<001), suggesting that breakdown ANt) FISHIi (Deparl- ment Medicine, School of 2-12 mm Hg (p<0-00)1); slow wave fre- of triglycerides to fatty acids is not essential of Wellinigtbon Medicine, Wellington 2, New quency 10-5-12-5 cpm (p<0.005); propaga- for ileal inhibition of gastrointestinal Zealand) The fate of the tion index 1-5 (p<0.001) and a progression transit. major SCFAs (acetate, from random activity at 28 weeks, through In summary we have shown that a range propionate, butyrate). in man which result repetitive fetal complexes to migrating of lipid substances, detergents and bile acids mainly from the fcrmentation of carbo- motor complexes by 37 weeks gestation. when infused either directly into the intact hydrate is largely unknown. We have studied Nutritive sucking only occurred after 33 ileum or into an isolated ileal loop delay fermentation in man by measuring thesc weeks gestation. Bolus feeds appropriate to SCTF of a bean meal. SCFAs in portal and peripheral blood, after http://gut.bmj.com/ of to the infants age produced no motor response the caecal administraition lactulosc patients maintained on free in the very preterm infants (28-30 weeks) polysaccharide but with increasing gestational age food before undcrgoing elective chole- HLA D/DR Ag expression in the jejunum of cystectomy. At operation portal and (p<0)005), volume of feed (p<0-001) and children with idiopathic protracted diarr- time exposed to feed (p<0001), the length peripheral venous blood samples were taken hoea (IPD) and circulating enterocyte anti- before, and at 15 minute intervals up to 60 of postprandial activity increased (0-140 bodies (EcAb) min). Disruption of fasting activity, minutes following, caecal injection of either 20 ml sterile saline (n= 12), or 67 g (n=6) or however, did not occur when low volume on September 26, 2021 by guest. Protected copyright. R MIRAKIAN, C A RICHARDSON, J A WALKER- It) g - were continuous feeds were used. These data (n= 10) lactulose samples SMITH, S HILL, P J MILLA, AND G F BOTAZZO suggest that the development of fasting analysed by GLC. Fasting levels (n=28) (Middlesex, Queen Elizabeth Hosp5ital, and were (,umol/l, mean+SD); portal acetate motor activity and nutritive sucking is Hospital For Sick Children, London) Small gestationally dependent whereas the post- 128±70-8, propionate 34-4+23-3, butyrate intestinal villous enterocytes express Class 17-6± 18-5; peripheral acetate 1, prandial motor response is dependent on 77-2±56 II molecules whereas crypt cells do not. The propionate 37±+12, butyrate traces only. the pattern of feeding. We speculate that role of such molecules in the gut is unknown the former mirrors central and enteric After lactulose there was a rapid rise in but it has been suggested that they may be portal SCFA, with mean peak levels (tmol/ neural development whilst the latter is more involved in maintaining tolerance to oral likely humorally related. I) after 10 g lactulose being acetate 197, antigens. In some children with IPD, circu- propionate 277, and butyrate 17 3 - the lating EcAbs are present together with response was dose related. No appreciable other autoimmune manifestations. Jejunal changes in peripheral SCFA were found. Effect of ileal infusion of fats, detergents and biopsies from nine children with IPD, In conclusion, the caecal fermentation of bile acids on stomach to caecum transit time EcAbs and an enteropathy were compared lactulose is rapid in man with aippreciable in the rat with histologically normal jejunum from increases in portal SCFAs. nine controls. We studied HLA Class I and NICOLA J BROWN, A RICHARDSON, R D E II molecule expression in the enterocyte RUMSEY, AND N W READ (Sub-Department of epithelium by immunofluorescence. HLA Gastrointestinal bleeding from other sources Human Gastrointestinal Physiology and Class I products were normally expressed in in patients with colonic angiodysplasia Nutrition, The University, Sheffield) We the jejunal epithelium of IPD patients. have recently shown that ileal infusion Class II (DR complex) expression in con- A C STEGER, R B GALLIANt), A IIEMINGWAY, C B intralipid (a triglyceride) significantly trols was restricted to upper villous entero- WOOD, AND J SPE.NCFR (Depts ofSuirgery atid Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1 356 The British Society ofGastroenterology Radiology, Royal Postgraduate Medical cystic fibrosis failed to respond when chal- Cystic Fibrosis Unit, Qlueen Elizabeth School, Hammersmith Hospital, London) lenged with the intestinal secretagogues Hospital for Children, London) Lactose In 5% of patients with gastrointestinal acetylcholine and prostaglandin E,, while intolerance has been described in children haemorrhage, the cause is obscure. Angio- control tissues exhibited a rise in potential presenting with cystic fibrosis, but little if dysplasia is increasingly found on colono- difference and short circuit current in any has been written about cow's milk scopy or angiography to be the commonest response to these agents. Both groups of protein intolerance in this disease. Children cause of bleeding in this group. Angio- tissues generated an increased potential with cystic fibrosis commonly present with dysplasia may be present, however, but not difference and short circuit current associ- failure to thrive. Causes include poor actively bleeding. ated with sodium linked glucose absorption. dietary intake, recurrent chest infections, In 71 patients with colonic angiodysplasia These results demonstrate for the first time and pancreatic enzyme insufficicncy. Itf and GI bleeding, 31 stopped spontaneously. that the defect in chloride transport children attending a paediatric cystic fibro- Of 40 that came to laparotomy, 31 had a observed in other epithelia in cystic fibrosis sis clinic continued to gain weight at less right hemicolectomy. In seven a small also exists in the jejunum and could con- than the normal velocity, even after ade- bowel lesion alone was removed (Meckel's tribute to the intestinal effects of the quate treatment for the above problems. diverticulum four, ileal carcinoid one, disease. The technique used should permit small bowel biopsy was performed (seven jejunal A-V malformation one, duodenal further studies of the basic defect and may cases). In five (aged less than one year) a diverticulum one). In two patients, both a be of diagnostic value. patchy enteropathy compatible with a histo- right hemicolectomy and excision of small logical diagnosis of cow's milk sensitive bowel lesions was performed. enteropathy, was seen. In all cases removal In the right hemicolectomy group, three of cow's milk (and lactose) from the diet died and seven rebled, four needing further Incidence, morbidity and mortality of resulted in improved weight gain, and stool surgery. In the small bowel lesion group, Crohn's disease in Scottish children consistency. Three underwent repeat small two of seven rebled, and one underwent a bowel biopsy which was normal. Four toler- right hemicolectomy. Neither of the two ROGER BARTON, SANDRIA GILLON, AND ANNF ated cow's milk by three years; the fifth patients having both lesions removed FERGUSON (Universitv of Edinburgh and remains on the exclusion diet at a year old. rebled. Western General Hospital, Crewe Road, On review of the clinical features, all had In 40 patients with angiodysplasia who Edinburgh) From Scottish hospital had cystic fibrosis diagnosed within a few came to surgery, 16 (45%) had a second inpatient records from 1968-1983, 282 weeks of birth. Three of the five had pre- lesion and four (10%) required further children were identified with the onset of sented with meconium ileus (overall only surgery. If the cause of GI haemorrhage is Crohn's disease (CD) at or before age 16. 10% do so). uncertain, full investigation including The incidence has increased four fold from Cow's milk elimination has a significant laparotomy is essential. If a synchronous 6-6/million age <16 in 1968 to 26-4/million impact on failure to thrive in some patients small bowel lesion is found it should be in 1983. This increase occured within the with cystic fibrosis (1:30 attending our http://gut.bmj.com/ removed at the same time as the colectomy. ages of 9-16, CD remaining rare under the clinic). Presentation with meconium ileus age of nine. A representative sample of 68 appears to be common in this group. cases was investigated in detail. Small bowel biopsy is an essential investi- The mean age at onset was 12-6 years, gation in those with cystic fibrosis with poor with a follow up of 7-05 (SD±4-2). Each growth in spite of adequate treatment. child spent 81-5 days (range 7-322) in PAFDIATRIC SFCTION hospital, with a mean of4-4 admissions up to the age of 20 years alone. Disease distribu- on September 26, 2021 by guest. Protected copyright. Absence of secretory response in jejunal tion and presenting features were similar to Simplified and accurate oral pancreatic biopsies from children with cystic fibrosis published large adult series. Forty patients function test for use in children (72°/0) have already required surgery, C J 'I'AYI OR, P S BAXTER, J HIARDCASTLE, AND P T 14-5% (10) have a permanent stoma. J W L PUNTIS, J 1) BFRG, 1) SU F, AND I W BOOTil HIARDCASTLE (Depts of Paediatrics and During the period of the study there were (Institute of Child Health, University of Physiology, University of Sheffield, five deaths, a mortality rate of 7/0. Birmingham, Birmingham) The use of 14-C Sheffield) The demonstration of reduced This unbiased, unselected cohort of labelled PABA in conjunction with the BT- chloride absorption and secretion across Crohn's patients show no unusual features PABA (Bentiromide) screening test for sweat duct and respiratory epithelia in cystic of the disease itself when presenting in pancreatic insufficiency (P1) is unacceptable fibrosis (CF) suggests that the disease childhood (although of course there are in children. We substituted p-aminlo- results from a specific defect in chloride significant effects on growth and nutrition), salicylic acid (PAS), a structural and permeability. Although GIT manifestations however, a substantial social and clinical pharmacokinetic analogue of PABA. for of the disease are common and secretory morbidity and mortality is seen. 14-C PABA. This modified test was evalu- processes in the normal intestine exten- ated in 28 children with PI (25 cystic fibrosis, sively studied no attempts have been made two Shwachman's syndrome, one pan- to identify a possible intestinal chloride createctomy), aged 17 months- 16 years, transport defect in CF. Cow's milk sensitive enteropathy: an together with a group of 20) control patients To address this problem the secretory important cause of failure to thrive in cystic aged 4 months-1 I years, shown to have activity of jejunal biopsies from children fibrosis in childhood normal pancreatic function by pan- with cystic fibrosis has been investigated creozymin secretin testing. After an over- using a modified Ussing chamber tech- S M HIll.l, M B MEARNS, AND J A WALKER-SMITH night fast, BT-PABA (15 mg/kg) with 4 5 nique. Samples from three children with (Academic Department of Child Health and mg/kg PAS was administered with a stand- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1 357 ard breakfast of cereal and milk. Following hood DU and adult DU. Unlike adults, earlier, based on strict diagnostic criteria. this, a six hour urine collection was made. paediatric patients not only have excessive The subjects had ranged in age from 7 to 14 After the alkaline hydrolysis of PABA and acid and gastrin response to stimulation, (median 12) years at diagnosis and from 25 PAS conjugates, urine samples were they also have increased basal acid and to 38 (median 3(0) years at follow up. Nine assayed by HPLC. The PABA Excretion gastrin secretion. The prognostic value of (47%) had had a proven ulcer on investiga- Index (PEI) was derived from the ratio of acid study in childhood DU is unique. tion, since entering adult life. Ten (53'.) PABA/PAS urine concentrations. The Findings of gastrin study in childhood DU, were no longer prone to recurring episodes mean PEI in patients with P1 was 19 (range never reported previously, suggest that this of abdominal pain but four of these had 4-60) and for controls, 87 (range 66-140), gastrointestinal hormone is implicated in undergone vagotomy and pyloroplasty for with complete separation between patients the pathogenesis of the disease in more than intractable symptoms in the past. Thus, with PI and those without. We conclude half of the patient population. only six patients (310%) appeared to have that the exocrine pancreatic status of child- made a lasting and spontaneous recovery. ren may be quickly and accurately determ- Complications such as haemorrhage, ined by a six hour oral test incorporating Campylobacter associated gastritis in penetrating duodenal ulcer, severe pyloric BT-PABA and PAS. children stenosis or perforation had occurred in 10 (53°%). Seven (37%) had undergone M J MAlHONY, J WYATT, AND J M LI5FLEWOOD surgery, and in two of these cases more than (INTRODUCED BY J KM.ILEHER) (Departments one operation had been performed. Fifty Pathophysiology of childhood duodenal eight per cent of all complications suffered ulcer of Paediatrics and Pathology, St James's University Hospital, Leeds) Gastric coloni- and 89% of all surgical operations per- sation by Campylobacter pyloridis is formed were in patients over the age of 21 P K H TAM (INIRODUC[F) BY PROFESSOR years. Our findings firmly reinforce the view R SH1IEL1DS) (Department of Child Health, strongly associated with non-auto immune gastritis in adults, where its significance that paediatric peptic ulcer disease fre- Royal Liverpool Children's Hospital, Alder quently persists into adult life and a risk of Hey, Eaton Road, Liverpool) Very little remains controversial. Its importance in children is unknown. Since 1981, 38 child- potentially life threatening complications pathophysiological data on childhood duo- remains many years after diagnosis. denal ulcer exist. Is the childhood condition ren presenting with persistent epigastric similar to or different from the common pain (aged 1-16, mean 10(3 years, 21 boys) adult disease? We studied gastric acid secre- have undergone upper gastrointestinal tion, emptying rate and serum gastrin con- endoscopy with gastric biopsy at this Gastro-oesophageal reflux in the preterm centrations in a group of children with hospital. These biopsies were studied retro- infant primary chronic duodenal ulcer and a group spectively for C pyloridis colonisation using the modified Giemsa technique, and for the I W of normal children as control. S.l NFWFIL, BOOIHi, M E I MORGAN, ANI) A S http://gut.bmj.com/ Both BAO and MAO were significantly presence of inflammation (Whitehead's MCNEISH (Regionial Neonatal Intenisive Care higher in DU (n=30) (mean±SD= classification). C' pyloridis colonisation was Unit, Birmingham Maternity Hospital, anid 0 16±0 12 mmol/kg/h, 0-55±0+16 mmol/ detected histologically in 9/38 (24%) cases, Institute of Child Health, University of kg/h respectively) than in normal (n=33) six of whom were boys. All patients were Birmingham, Birmingham) The incidence, (t)09±0*06 mmol/kg/h, 0-30±0-11 mmol/ aged 1t) or over, 9/28 (32%) being positive severity and importance of gastro- kg/h) (p<0-01). In addition patients with in this group. Eight of the ten patients with oesophageal reflux (GOR) in the pre-term more severe disease (n= 15) had higher chronic gastritis were C pyloridis positive; infant is unknown. Twenty four hour intra- MAO (0-63+0-17 mmol/kg/h) than those one of six cases showing only small focal oesophageal pH monitoring was performed with mild disease (n= 15) (0-47+±017 mmol/ accumulation of lymphocytes was positive, using a novel 1 mm antimony pH electrode on September 26, 2021 by guest. Protected copyright. kg/h) (p<0 02). while all 21 with normal gastric histology (Synectics Medical) and lower oesophageal Gastric emptying rates were similar in were negative. We detected C pyloridis in sphincter pressure measured. DU (median=6-8 min) and normal (7-0 32% children aged 10 or over endoscoped Fifty six measurements were made on 34 min), (p>0-01). Fasting serum gastrin con- for epigastric pain. The association between patients (postconceptional age: median 31, centrations were significantly higher in DU Cpyloridis and chronic gastritis in children, range 26-29 weeks). Mean (±SEM) indices (n=25) (60-4+9-7 pg/ml) than in normal in whom gastritis is generally uncommon, of GOR were as follows: 12-1+2 episodes of (n=25) (38 0+4-2 pg/mI) (p<0(05). supports a causal relation between the GOR per 24 h; pH was <4 for 45 ±0/ 9'Yo Integrated gastrin response to meal stimula- bacteria, gastric inflammation and epigastric of the total time; the longest episode during tion was also significantly higher in DU symptoms. each recording was 17±4-6 min. There was (14-9+2-2 ng min/ml) than in normal no correlation between GOR and post- (6-45±0-9 ng min/ml) (p<0.001). There conceptional age, gestation, or lower oeso- was no significant correlation between acid Peptic ulcer in childhood: the longterm phageal sphincter pressure. secretion and gastrin levels. prognosis The effect of nursing care upon GOR was Of the 25 DU patients, 11 had hyper- assessed. Gastro-oesophageal reflux was gastrinaemia (mean±2 SD) alone, six had M S MURPHIY AND F. J EAS[HAM (Department of most likely to occur at the time of physio- acid hypersecretion alone, two had both Child Health, Royal Victoria Infirmary, therapy, oropharyngeal suction, and nappy hypergastrinaemia and acid hypersecretion Newcastle upon Tyne) Information is change (p<0(001), and was increased after and only six had both normal gastrin and limited concerning the longterm prognosis feeds (0-05 A 1 358 The British Society ofGastroenterolog,x six infants with recurrent apnoea had mark- endoscopic intubation for inoperable oeso- propagating swallows, and confirnied the edly severe GOR (p<0.00(). A rapid reduc- phageal carcinoma. It was not possible to manometric diagnosis of achalasia (6/6) and tion in the frequency of apnoea followed directly randomise into laser versus intu- diffuse oesophageal spasm (2/4). The abolition of GOR with thickened feeds. bation, as most patients were not suitable remaining three patterns of abnormal OE l These results provide important physio- for immediate intubation (because of com- did not significantly correlate with specific logical data and have implications in the plete obstruction or tortuous tumour). manometric parameters or symptonil score. nutritional care of the very low birth weight Patients were randomised into laser The solid bolus oesophageal transit test baby. followed by repeat laser endoscopy every provides an objective screening test of oeso- four weeks (L), or initial laser therapy to phageal motility disorders and should be ensure a suitable lumen to allow dilatation performed before oesophageal manometry. and intubation (1). Forty five consecutive patients were treated (20)1 2(01 and five exclusions). Swallowing ability was H2 antagonists in oesophagitis: can physio- OESOPHAGUS recorded on a 0)-4 scale (0=swallowing all logical studies predict the response? solids, four=total dysphagia). Quality of Factors influencing survival in oesophageal life was assessed by the QL index (scale I) A F ROBTIRSON, M A ALDERSIFY, 11 cancer 1)-11)) and a linear analogue self assessment SHEPIIPRI), R S lLOYD, AND C 1. SMI-I1I1 ()('- (LASA, scale 0)-20)0)). Mean swallowing partment of' Medicinie I1, Southainpton A WAI SON (Royal Lancaster Infirmary, grade pretreatment was 2.9+±).8(L) and General Hospital, Southampton) The Lancaster) Survival after resection for 2-8+0-9(I) (NS). The best post treatment response to H. antagonists in reflux oeso- oesophageal cancer is poor, five year survi- was 0.9+0.9(L) and 16±1)5(1) (p<().002). phagitis is disappointing with only 50)%/ val rate (5YSR) seldom exceeding 15% in The QL and LASA improved by 017 and of patients healing. In an attempt to the West, although 5YSR greater than 50%)' 13-1(I) and by one and 20-1(L). Seven identify factors predicting response we for superficial lesions is reported from (I) and three (L) developed recurrent have measured; ambulatory oesophageal Japan. It is unclear whether this relates to dysphagia with seven (I) and two (L) having pH, oesophageal manometry and fasting earlier detection or a different form of the complications. Laser therapy offers more serum gastrin concentrations in 28 disease. This study was undertaken to effective palliation for matlignant dysphagia patients with reflux oesophagitis, before investigate the relationship between than intubation. and during treatment with ranitidine tumour staging and survival in 49 patients 31)1) mg bd. Fourteen patients healed undergoing resection between 1975- 81 pre- endoscopically at six weeks (group A) viously presented to this Society. Forty and 14 had residual oesophagitis (group three of these have now been followed for at Manometric interpretation of the oeso- B). Group A were characterised by a least five years and stratified according to phageal egg transit test: a useful screening lower serum gastrin level before treat- http://gut.bmj.com/ cell type, depth of tumour invasion and test for oesophageal motility disorders ment (4-52 pmol/l; 24-10): mean and contiguous lymph node status. range) and group B (11*1 pmol/l; 3-5-21: Five year survival rate in resected C A ERIKSFN, R J 010LDSWORti, D SUTITON, p<0-05) and showed a marked reduction patients was 14 3%, overall and 16.3% in N KENNFDY, AND A CUSCHIERI (Departments in acid reflux on treatment to near those surviving resection, representing of'Surgery and Nuclear Medicine, Ninewells normal values. Mean /O time below pH4 29-4% for squamous and 7-7%/ for adeno- Hospital & Medical School, Dundee) The fell from 14-9 to 4-2 in group A (p<0-05) carcinoma. Nodal involvement occurred in use of manometry to detect oesophageal but was not affected in group B ( 14-2- disorders in its 58-8%Yo of squamous and 80-7% of adeno- motility requires expertise 15-6, not significant). Severity of reflux. on September 26, 2021 by guest. Protected copyright. carcinoma, where 5YSR was 10% and 0'/o performance and interpretation. The oeso- degree of oesophagitis, lower oeso- respectively. In node negative cases, 5YSR phageal egg transit test (OET) uses a phageal sphincter tone (Group A 27-8 mm was 57. 1% for squamous and 40% for standardised 99mTc solid egg bolus to Hg, group B 26-8 mm Hg), age, sex, adenocarcinoma. 23-6(o of squamous and objectively and physiologically evaluate smoking, obesity, duration or severity of no adenocarcinomas were confined to the oesophageal transit. We assessed the symptoms were not significantly associ- oesophageal wall, 5YSR in this group being oesophageal motility of 102 symptomatic ated with healing. Abnormal peristalsis 75%. patients using oesophageal manometry and was common (29 4% abnormal waves Depth of invasion and nodal status are OET. Of 32 patients with normal OET, 10 group A, 36% group B, NS) but did not better prognostic discriminants than cell (310%) had abnormal manometry (7/11) inhibit the response to ranitidine, and type. Survival in the minority of lesions being diagnosed non-specific oesophageal did not improve with healing. Healing detected early is comparable to that of motility disorder). Of 70 patients with with H. antagonists in oesophagitis is Japanese series and to equivalent stages of abnormal OET, 51 (730%) had abnormal due to reduction in acid reflux, with no other tumours. manometry (x2=1582, p<0-001). The effect on oesophageal motility. The computer generated condensed image response cannot be predicted before defined five different transit patterns: treatment. Laser therapy or intubation for palliation of normal (n=32); oscillatory (n=21); non- malignant dysphagia clearance (n= 16); 'step' delay (n= 16); miscellaneous delay (n= 17). Normal OET Treatment of reflux oesophagitis with a H BARR, N KRASNER, A RAOUF, AND R J WAL KER correlated significantly with normal prostaglandin analogue (Gastrointestinal Unit, Walton Hospital, manometric parameters. Oscillatory Liverpool) A prospective randomised trial OET showed significantly more tertiary HI L SMART, P D JAMES, M AFKINSON, AND C J was done to compare laser therapy with contractions, low amplitude waves and non- IIAWKEY (University Hospital, Nottingham) Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1 359) The prostaglandin analogue trimoprostil is varices while incorrectly suggesting varices Uiit, s UMDS s St homa' Campus, of GuY & gastro protective, inhibits acid secretion in their absence endoscopically in six Thomcas'Hospitals, Lonidoni) The BBGSG's and does not reduce lower oesophageal patients specificity 910. trial was a prospective, multicentre, random sphincter tone. We therefore assessed its We conclude that ultrasound can identify allocation trial of low dose ursodeoxycholic value in reflux oesophagitis. oesophageal varices with high sensitivity acid (UDCA) 3 mg/kg/day, placebo (double Twenty two patients received trimopro- and specificity and should be specifically blind) or high fibre low refined CHO diet in stil 750 btg qds and 22 received placebo in a examined for in all patients with suspected preventing gall stone (GS) recurrence in one month double blind controlled clinical chronic liver disease. patients with confirmed complete dis- trial. Both groups were allowed antacids. solution. Ninety three patients, stratified Patients treated with trimoprostil (but not for obesity and stone free intervail since placebo) experienced a significant reduc- Prospective controlled trial of propranolol dissolution, have been followed for up to tion in the frequency of pain, from seven and sclerotherapy for prevention of rebleed- five years (28+SEM 1-5 mo) with six months (median, range 1-7) days/week (p<0.005) ing from oesophageal varices ultrasound (US) and yearly cholecysto- and in its duration, from two (1-12) to 0-5 grams (OCG). (0-6-5) hours/day (p<0-02). Both groups C VICKI-RS, J RHOI)ES, P HI111ENBRAND, There were 21 recurrences, only two reported a reduction in the severity of pain H BRADBY, P HAWKER, P D)YKIS, I CII[SNER, symptomatic, 21±2 mo (range 12-42) after and sleep disturbance during the trial but R COCKEL, D ADAMS, R VAl ORI, J DAWSON, trial entry, equivalent to 9'0±3-2'2, at 1, differences between them did not reach H O'CONNOR, AND E ELIAS (Qtueeni Elizabeth, 23-4±500 at 2, 30-5+6%/, at 3 and 35-5±7-5 statistical significance. There was a sig- Good Hope, Genieral, Sell*vOak, East at three and a half and subsequent year, by nificant reduction in the extent of oeso- Birmingham, acnd Santdwell Hospitals, life table analysis. Recurrence was greater phagitis seen at endoscopy after treatment Birmingham) Sclerotherapy is of value in and earlier by US than by OCG. There were with trimoprostil from 5 (1-9) cm to 3 (0-9) the treatment of acute variceal haemorr- four recurrences in the UDCA, six in the cm (p<0(00l). At the end of the trial eight hage although rebleeding occurs in up to placebo and 11 in the diet groups, corres- patients taking trimoprostil showed no 55% of patients. We have evaluated the role ponding to 23-5±10(8/%, 30-6±118Xo and endoscopic evidence of oesophagitis. of additional longterm propranolol to 46-4 14-2% respectively at three and a half Trimoprostil was well tolerated and further reduce the rebleeding rate and years. Recurrence rates for UDCA and diet appears to bc an effective treatment for improve survival. Sixty nine patients (41 treated groups were not significantly differ- oesophagitis. Prostaglandins may be cyto- M), admitted with bleeding varices to a ent from those taking placebo. Age, protective to the human oesophagus. district hospital, were randomised to obesity, weight change and pregnancy did receive regular sclerotherapy, plus pro- not affect outcome, but men showed more pranolol 160 mg (long acting) (n-35) or frequent recurrence than women (NS). The placebo (n=34). Median follow up was 96 stone-free interval between dissolution and and 110 weeks respectively (range 44-233). trial (median 9 mo), was important - the http://gut.bmj.com/ Ultrasound identification of oesophageal Both groups were similar for age, sex, recurrence rate at three and a half yeair varices - comparison with endoscopy aetiology, and Child's grading. being 62-9±13-4% for <9 mo and 15 7+ Interim analysis on 'intention to treat', 7-50/, for >9 mo (p<0-02). S H SAVERYMUITIU, A E A JOSEPH, AND J D 55% of propranolol and 71 % of placebo Neither low dose UDCA nor diet are MAXWI.I I. (Depcartments of Medicine II and treated patients were free of rebleeding effective in preventing GS recurrence. Ultrasoutd, St George's Hospital and (p=NS). Median time to rebleeding was 15 Patients who remain GS free for several mo Medical School, London) Oesophageal weeks (1-130) in the propranolol and nine without treatment constitute a 'low-risk' varices are an important feature of chronic weeks (1-94) in the placebo group. There group. More than 50% of patients remain on September 26, 2021 by guest. Protected copyright. liver disease and are currently recognised by were 22 deaths (propranolol 13) with GS free for up to five years. endoscopy or radiology. Because ultra- rebleeding responsible in 13 (propranolol sound is routinely used as the initial assess- nine). Cumulative per cent survival was ment of chronic liver disease the identifica- 58% in the propranolol and 72%'/ in the tion of oesophageal varices at this time placebo group (p=NS). Interdigestive gall bladder emptying and its would aid both investigation and manage- The results show that in patients under- relationship to motor activity in man ment. We have attempted to directly visua- going regular sclerotherapy after an episode lise oesophageal varices by ultrasound of variceal haemorrhage, longterm pro- S ELI-ENBOGEN, J S GRIME, J CALAM, C R examination of the lower oesophagus in a pranolol confers no additional benefit in MACKIE, S A JENKINS, AND J N BAXTI R prospective comparative study with upper survival or prevention of variceal rebleed- (Department of Surgery, University oJ gastrointestinal endoscopy in 100 patients ing. Liverpool, Department of Nucear Medicine, with suspected or proven liver or biliary Royal Liverpool Hospital, Dept of Gastro- tract disease. Oesophageal varices were enterology, Royal P G Medical School recognised on ultrasound by thickening of London) Human gall bladder emptying the oesophageal wall and irregularity of the (GBE) occurs during both digestive and air containing lumen. In seven patients GAL LBLADDER interdigestive periods. The mechanism for ultrasound was unable to adequately visua- interdigestive GBE is unknown but may be lise the oesophagus while in four patients The British/Belgian Gallstone Study Group's related to the intestinal migrating motor endoscopy was equivocal. Excluding these (BBGSG) postdissolution trial complex (IMMC) (fasting cyclic and phasic two groups ultrasound detected 18 of 22 intensity activity). Using "Tc'0-EHIDA oesophageal varices (sensitivity 82%) K HOOD, D GlIEESON, D C RUPPIN, R I1 cholescintigraphy and gastrointestinill including all patients with medium or large DOWLING, AND T1HE BBGSCi (Gastroenterology manometry, interdigestive GBE and the Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1360 The British Society of Gastroenterology IMMC were observed in two groups of at six months but partial GS dissolution at and Pathology, Royal Infirmary, Glasgow) healthy volunteers; group I, observed for 12 months. No patients with suspected non- Both increased and decreased gall bladder 134-298 minutes without stimulation (n= chol stones responded to treatment. There contraction are described in the presence of 18); group II, observed for 90) minutes after were no abnormalities of liver function or gall stones and an altered sensitivity to atropine (0-6 mg+0'3 mg/kg/h) (n=8). In serum lipids and no acquired GS calcifica- cholecystokinin has been implicated. We group 1, 17 complete IMMC cycles were tion but 11 had diarrhoea- transient in four, have examined in vitro gall bladder con- recorded. The cycle length was 100±15-5 but requiring CDCA dose reduction in five tractility and sensitivity to cholecystokinin minutes, and the lengths of the phases were; and withdrawal in two. octapeptide (CCK-8) in 42 patients with gall phase I, 35-3±6-6 minutes; phase II, (1) Pretreatmcnt SI <1 0 predicts lack of stones and in 14 'control' patients having 60(6±10 4 minutes; and phase III, 5-2±0 3 response. (2) CDCA+UDCA have lower cholecystectomy during hepatic artery can- minutes. Interdigestive GBE occurred on efficacy (44-5±12 5% at one year) but few nulation. Full thickness strips from the body nine occasions; four during phase I, and five side effects than single bile acids. (3) With- of each gall bladder were suspended in during phase II. In 10 of the IMMC cycles, drawal of treatment for non-response oxygenated Krebs' solution at 370C. Dose GBE did not occur, whilst in two cycles should be delayed until one year. response curves were obtained to CCK-8 GBE occurred twice. The relationship (10 "-10( M). The concentration of between spontaneous GBE and the phases CCK-8 required to achieve 50% of maxi- of the IMMC was random (p<025,X2 In vivo choledocholitholysis using methyl mum contraction (ED,,,) was taken as a goodness of fit). The gall bladder emptied tertiary butyl ether (MTBE) measure of sensitivity. Muscle contractility 181±0-4% of its contents (mean±SEM). was derived from the maximum contraction I, any and the muscle volume of each strip. From group the probability of GBE in G A LAFERILA, G FULLIERTON, AND W R MURRAY minute period was calculated as 0-0053. (University Department ofSurgery, Western Median contractility in the normal group Atropine inhibited GBE in all eight group II Infirmary, Glasgow) The management of was 60 g/cm (range 28-96) which wtas volunteers during the 90 minute study choledocholithiasis has been revolutionised significantly different from gall bladders period (p<0001, Poisson test, group II v by endoscopic sphincterotomy. Stone with stones (median 25 g/cm3, range 4-1t)2) group I). extraction through the sphincterotomy is (p=t)0002 Mann Whitney). There was no These results suggest that interdigestive limited by their size. If extraction fails a difference in ED,, values between the GBE (1) occurs infrequently and in small nasobiliary catheter (NBC) can be placed groups (normal: median 40-7 nM, range volume, (2) is unrelated to the phases of the endoscopically thus allowing access to the 0-05-100) (gall stones: median 40(7 nM, IMMC, (3) is cholinergically mediated. stones for dissolution therapy. We present range 9-200). our preliminary experience using the We have confirmed that gall stoncs are aliphatic ether MTBE. Ten patients (eight associated with a significant reduction in gall bladder contractility without any Bile lipid and gall stone (GS) dissolution men, two women; age range 65-85 years) http://gut.bmj.com/ were change in sensitivity to CCK-8. responses to combined chenodeoxycholic with suspected choledocholithiasis acid (CDCA) and ursodeoxycholic acid referred for ERC, six having previously (UDCA) treatment undergone cholecystectomy. Endoscopic cholangiography confirmed multiple (2-12) Stone extraction after endoscopic sphinc- K HOOD, D GLEESON, G M MURPHY AND R H large stones (diameter 15-I mm-27 5 mm). terotomy - and active policy is best DOWlINCi (Gastroenterology Unit, Guy's Post sphincterotomy extraction failed in all Campus, UMDS of Guy's and St Thomas' cases. An NBC was inserted and 24 hours D F MARTIN, J C MCGREGOR, M E LAMBERT, AND Hospitals, London) Oral CDCA dissolves later MTBE dissolution was commenced D E F [WEEDLE (Gastrointestinal Unit, on September 26, 2021 by guest. Protected copyright. radiolucent GS with moderate efficacy but using 2-5 ml of the solution every 3t) University Hospital of South Manchester, An causes dose related diarrhoea and hyper- minutes over a two hour period. average West Didsbury, Manchester) In order to transaminasemia. Ursodeoxycholic acid is of four dissolution sessions were used per evaluate a policy of primary stone extrac- free from these side effects but has lower patient. Subsequent stone assessment tion after endoscopic sphincterotomy (ES) efficacy, in part because of acquired GS revealed complete disappearance in three we have reviewed the success and complica- calcification. To minimise side effects whilst patients, significant reduction in stone size tions of this procedure in 262 patients seen in five maintaining efficacy, we gave 7 5 mg allowing subsequent duct clearance between January 1981 and December 1985. and no in two. CDCA plus 5 mg UDCA kg/day (half patients change Complica- In 85 patients whose bile ducts were cleared normal doses) to 34 patients (6 M, 28 F) tions noted were mild drowsiness (one of stones immediately after ES, acute pan- and nausea Minor aged 23-91 (median 51) yr with radiolucent patient) (one patient). creatitis developed in three (3.50/o) and in GS measuring 8 7+SEM 0 9 mm max diam transient abnormalities liver function another (1 22%) died from a pancreatic This effective in 'functioning' gall bladders. Biliary chol tests occurred in all patients. abscess after initial admission with acute be of satn index (SI), measured in 15, fell from agent, which has a low morbidity may pancreatitis. None developed any other 1 11±0 09 before (SI<1 0 in five suggesting value in the management of the frail and complication. In 177 patients whose stones non-chol stones) to 0(8±0)06 after six weeks elderly patients with large bile duct stones. were not cleared, 56 had insertion of a treatment. Fourteen were treated <6 mo pernasal catheter. Eight of these (10(2%) (surgery in four, default in three, three to developed complications, two (3.4%o) of five months treatment in seven). Of 20 Gall bladder motility in the presence of gall which were cholangitis related to tube followed >6 mo, three showed complete stones blockage or displacement. In the remaining and five partial GS dissolution correspond- 121 patients, stones were left without drain- ing to 44-4±12 5% at one year by life table G T SUNDERLANI), C Gi SUIHERILAND, AND D C age. Complications developed in 18 analysis. Two patients showed no response CARTER (University Departments of Surgery (15.2%) but eight of these had bleeding Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 1 36 1 which precluded attempts at extraction. R MILLER, D C C BARTOtO, A M ROE, N J MCC (control/haemorrhoid/incontinent; ME Four patients (3-3%) developed cholangitis MORTENSEN, AND [) JAMES (Department of (mv): lower 4-0/4-3/7-0', middle 4t)/5 55' alnd another (0(8X%) cholecystitis despite Surgery, Bristol Royal Infirmnary, Bristol 8X0", upper 5-5/12-1'/1-5", MDTC °C: intravenous antibiotics. Two patients and Department of Clinical Measurement, lower 08-/1-2'/2-2", middle )-9/1-2|/2-22, (I *6%) died. Although development of Royal Devon and Exeter Hospital, Exeter, upper 1(0/3- 1"/>4-5'). complications of ES, particularly bleeding, Devon) Water filled microballoon mano- We believe that impaired anal sensaition may lead to failed duct clearance, it appears metry systems have many disadvantages may be an important contributary factor to that infective complications are more likely and microtransducer tipped catheters the pathogenesis of faeccal incontinence. when duct clearance fails. An active policy (MTC) have been advocated as reliable Lesser degrees of sensory loss related to of primary stone extraction with the use of alternatives. Maximum resting (MRP) and haemorrhoidal prolapsc is not associated pernasal catheters or stents when this fails, maximum voluntary contraction (MVC) with incontinence in the presence of good may be expected to reduce the risk of pressures were compared using the two sphincter function. cholangitis. systems with a standard station pull through (Significant difference from controls: technique in 12 patients. There was poor a=p A1362 The British Society ofGstroenterology University, Canada) As previous reports on 115+0-5 at 120 seconds. EMG showed no due to outlet obstruction (00) as shown by defecography suffer from the absence of change in puborectalis/anal sphincter failure to evacuate rectal contents on datita on normal subjects, we recruited 48 activity during the instillation of barium. proctography or by electromyographic healthy young adult student volunteers (25 Expulsion of barium was achieved by evidence of increased puborcctalis activity men and 23 women) to undergo a defeco- further increasing anorectal angle to 134±5 on attempted detecation (n =26). Alternat- gram. For the procedure, after coating of degrees and decreasing anal canal pressure ively, patients may have colonic inertia (CI) the rectal mucosa with liquid barium, a to zero mm Hg as a consequence of aboli- as demonstrated by failure to achieve an barium paste was inserted into the rectum. tion of puborectalis/external sphincter increased motility index after rectal The external anal orifice was marked with EMG activity. These results suggest that bisacodyl or where passage of radio opaque barium ointment, and women inserted a elevation of the levator ani occurs before markers is delayed (n=4). Some paitients contrast soaked vaginal tampon. Video relaxation of the puborectalis during have both 00 and Cl (n= 10). Anorectal fluroscopic recordings in the lateral position defecation. Failure of this coordinated myectomy (ARM) gives good results in with 10() mm spot films were taken at rest, activity may be the basic abnormality in piatients with 00 whereas subtotal with contraction of pelvic muscles, on patients with symptoms of obstructed colectomy is reservcd for patients with Cl. straining and during defecation. Twenty defecation. We hiave reviewed the results of ARM for variables were measured directly using a 00 with normial transit (60% 100% centimetre midline scale. Ten radiographic marker passed in five datys) and those with appearances were also recorded and 00 and/or CI (less thian 60%'/ markers graded. Does the position of the patient influence the passed five days). ARM aIchieved passage T'he results indicate the range of norm- results of anorectal manometry? of at least three stools per week without ality to be much wider than previously laxative in 1t) of 12 patients (83%O) with 00 realised; for example 44% of men and 45%0 K YOSHIOKA, V POXON, AND M R B KEIGHILI Y who have normtil transit compared with of women had a high grade intusussception, (Surgical Department, The General only eight of 16 patients (500/%) with 00 77% of women had an anterior rectocoele Hospital, Birmingham) We have compared and/or Cl. Six patients with 00 and/or (moderate to large in 9/23). The mean measurement of pressures at 2, 4, and 26 cm CI have subsequently required subtotal pelvic descent from rest in women was 2-0 from the anal verge using an open tipped colectomy which restored bowel habit to cm and greater than 3 cm in 23%. In men perfused catheter in three groups of normal in five paitients (83%O) and none the mean was 1.9 cm, with 20()/ greater than patients: controls (n= 1), constipation developed incontinence after a previous 3 cm. Four subjects had an open anal canal (n=21) and incontinence (n= 14). Pressures ARM. at rest with apparent incontinence. Caution were measured at rest (R), during maxi- must be exercised in overinterpreting mum pelvic floor contraction (Sq) and defecograms of patients. attempted defecation (St) in the left lateral (LL) and seated position (S). No significant Clinical and physiological evaluation of http://gut.bmj.com/ difference between the seated and lateral postanal repair position was observed at 2 cm in all groups. Physiology of defecation - the importance of At 4 cm, there was no significant differ- K YOSHIOKA, (G IIYILAND, ANI) M R B K(GilIl I-EY the levator ani muscles ence in control group, whereas significant (Surgic al Department, Th)e Genierail differences were observed in the group of Hospital, Birmin1gham) Postanal repairl I (G FINILAY, K (CAR'I'ER, AND) I MCILOED (INTIRO- patients with incontinence (R:p<0(025, (PAR) is used for treatmenit of idiopathic D)UCIH) BY D C CARTIFR) (University Dept Sq:p<0).0)25) and the group of patients with faecal incontinence (IFI) on the premise that Slurgery, Royal Infirmary, Glasgow) constipation (R:p<0(025, St:p<0.()5). At it restores a deficient anorectal angle. We on September 26, 2021 by guest. Protected copyright. Coordinated relaxation of the puborectalis/ 26 cm pressures were significantly greater in have rcviewed the longterm results of PAR anal sphincter muscles resulting in an the seated position for patients with incon- in 124 patients between 1976 and 1986. Wc obtuse anorectal angle is necessary for tinence (R:p<0.01, Sq:p<)-0 1). Compli- have measured anal and rectal pressurcs, unobstructed defecation. The factors which ance (ml/cm H20) did not differ significantly rectal compliancc, anal and rectal sensattion initiate this mechanism are unknown. We with position in controls (LI-848, and performed proctograms before and used videoproctography. micropressure S= 13-08), incontinence (LL= 14-82, three months after operation (n=9). transducers and EMG to simultaneously S=16-34) or constipation (LL= 10-97, Results arc compared with age and sex study anorecal angle, intrarectal/anal canal S=11-77). Measurement in the left lateral matched controls. Only 24 (34%O) of the 79 pressures and external sphincter/ position is unphysiological and differs sig- patients followed for more than three years puborectalis/levator EMG in five normal nificantly from the seated position particu- claimed complete continence. Although 50 patients. The call to stool was initiated by larly in incontinent patients. (69%/) were improved, soiling occurred in the instillation of 180 ml barium (1-25 43 (62%O) and 4t) (56(%) continued to wear mg/ml) over a 120 second period. Observa- pads. Resting (R) aind squeeze (S) anal tions were made during the insitillation aind canal pressurcs were significanitly lower in voluntary expulsion of barium. Physiological parameter should dictate the IFI thanl controls (R:49-7 v 83-0, p<0-0l, The instillation of barium produced (a) a surgical management of longstanding idio- S:77-2 lo 130(9, p<0-005) there 'was no mean fall in anal canal pressure from 40± 16 pathic chronic constipation significiant improvement in anal pressures mm Hg (mean±SE) to 13±8 mm Hg. (b) A after PAR (R before and after: 49-7 v 47-3, rise in intrarectal pressure from 0 to K YOSIIIOKA AND M RB KEIGHLEY (Surgical S before and aifter: 77-2 v 691, NS). 30(5+12 mm Hg (c) An increase in Department, The General Hospital, Furthermore there was no objective anorectal angle from 86±5 degrees to Birmingham) We have found that idio- improvement in anal sensation (lower zone 103±7 degrees at the call to stool and pathic longstanding constipation may be before and after PAR: 137 mA and 144 mA, Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A1363 NS). The resting anorectal angle was sig- ascertains the nature and proximal extent of pressure: 60 (0-120) cm HO l' (1(00-21(0), nificantly more obtuse in IFI than controls the motility response to sacral nerve root p<0.0)021. Rectal sensation was similar in (130.6 v 114-1, p<0-025) but PAR had no stimulation in six male paraplegic subjects. both groups. This is the first report of a influence on resting angles (pre and post: With endoscopic access, pressure record- significant sensory deficit in the anal canal in 130-6 v 131-8, NS). Although incontinent ings were taken from the transverse colon combination with a motor neuropathy in a patients have obtuse anorectal angle post and continued distally using conventional group of patients with primary neuropathic anal repair is associated with no physio- manometric methods. There was a pressure faecal incontinence. logical change and results were disappoint- increase in response to S2 and S4 (15±10 cm ing. of water) but S3 stimulation caused the greatest pressure response (45+2() cm of Sensorimotor pelvic floor neuropathy: a water). This response affected all of the left comparison of diabetes mellitus and idio- Action of cisapride on intractable constipa- colon but in three subjects began 10 cm pathic faecal incontinence tion associated with spinal and pelvic nerve proximal to the splenic flexure confirmed injury radiologically. In the lower left colon the J ROGERS, J J MISIEWICZ, AND MM HENRY motor responses were peristaltic propa- (Department of Gastroenterology atnd N R BINNIE, P EDMOND, AND A N SMITHI (Spinal gated distally between three pressure trans- Nutrition, Central Middlesex Hospital, Injuries Unit and Castro-intestinal Unit, ducers in series. This study establishes that London) Diabetic neuropathy is common, Western General Hospital, Edinburgh) the extent of colonic motor response to but pelvic floor function has not been invest- Interruption of the parasympathetic nerves sacral root stimulation extends from or even igated in this condition. We studied 21 to the colon, in the spinal canal or in the proximal to the splenic flexure and suggests diabetics (DM), mean age (range) 55-3 pelvis, results in lessened colonic motility that the S3 root is the dominant spinal nerve (36-72) years, 18 patients with idiopathic and constipation. Simulating nerve stimula- root for elicitation of motility responses in faecal incontinence (IFI), 54.1 (25-83) tion by the release of ACH at the myenteric the left colon. years and 11 age matched controls. All plexus should correct the colonic dysmo- diabetics had peripheral sensory neuro- tility. Cisapride releases ACH at the pathy but none had faecal incontinence. myenteric plexus. Oroanal transit time Combined sensorimotor deficit in primary Pelvic floor motor function was assessed by (OATT) has been studied in 15 patients neuropathic faecal incontinence calculating fibre density (FD) from single who related the onset of their constipation fibre EMG of external anal sphincter; to the time of spinal cord injury (n=10) pudendal nerve terminal motor latency J ROGERS, J J MISIEWICZ, AND M M HENRY or pelvic surgery for hysterectomy (n=5), (Department of Gastroenterology, Central (PNTML); and anal canal manometry. before and after oral administration of Middlesex Hospital, London) Patients with Sensation was assessed by balloon disten- cisapride. During the study each patient idiopathic faecal incontinence (IFI) often sion of the rectum and mucosal electro- acted as his/her own control. Before report that they have no sensation of sensitivity (MES) of the anal canal. FD was http://gut.bmj.com/ cisapride, both groups of subjects showed impending or actual incontinence. We have significantly (p<0-01) increased in DM and delayed OATT (spinal group 187±87 studied 11 patients with IFI, eight women, IFI compared with controls [median hours, hysterectomy group 130+76 hours) mean age (±SD) 56-2±16-9 yrs and nine (range): 1-82 (1-42-2-57) and 2 07 (1-21- the passage of the 'Hinton markers' as a normal controls (NC), four women, 56-6± 2.37) v 1-38 (1-06-1-60))], respectively. bolus in 1-7±0-5 stools. With cisapride 15-9 yrs with techniques of mucosal electro- Mucosal electrosensitivity showed a signifi- there was a significant reduction in OATT sensitivity (MES) and rectal distension for cant (p<0.0l) sensory deficit in the upper, (spinal group now 125±73 hours; hyster- the quantitative assessment of anorectal middle and lower thirds of the anal canal in ectomy group 81+31 hours) and the sensation. Pelvic floor motor function was DM and IFI compared to controls, 18-2 on September 26, 2021 by guest. Protected copyright. markers passed in 3-2+ 14 stools. The assessed by calculating fibre density [(FD), (3-1-13-5) mA and 11-2 (5-2-25) v 5-3 motility effect is predominantly on the an index of denervation/reinnervation], (3-4-6-9); 6-2 (2-7-10-7) and 7() (2-1-21.4) colon as the small bowel transit was 3-2±1-3 from single fibre EMG's of the external anal v 3-7 (1-7-7-2); 6-2 (2-9-17.5) and 5-7 hours before and after cisapride 2-8±0-7 sphincter; pudendal nerve terminal motor (8-2-21-6) v 4-0 (2-0-6-2)J, respectively. hours. Faecal water content in stool speci- latency (PNTML); and anal canal Pudendal nerve terminal motor latency and mens remained unchanged (62.5% and manometry. manometry were similar to controls in DM. 630o). Mucosal electrosensitivity showed a sig- In IFI PNTML significantly (p<0(01) nificant (0.001 A1364 The British Society ofGastroenterology W M SUN ANI) N W READ (>Sub-Department of threshold volume for perception, desire to Road, London) There is no information on Huimlatn Gastroinitestinal Physiology and defecate and for discomfort or pain were all the IAS in neuropathic faecal incontinence. Nutrition, K Floor, Royal Hallamshire significantly lower in IBS patients than in Six women with major neurogenic faecal Hospital, Sheffield) Anorectal pressures at normal subjects. Nicardipine significantly incontinence were studied by anal mano- rest, during squeeze and straining to blow increased these volumes in IBS patients but metry, pudendal nerve terminal motor up a balloon were measured in female not in normal controls, and also reduced the latency, external sphincter (EAS) single patients, six with full thickness rectal pro- contractile and symptom response to a meal fibre EMG, and IAS surface EMG. An IAS lapse (RP), 12 with anterior mucosal pro- in IBS patients. The results from this study biopsy obtained during postanal repair lapse (AMP), and six with solitary rectal suggest that nicardipine could reduce the (PAR) was tested in vitro for myogenic tone ulcer (SRU) and in nine female, age activity of colonic smooth muscle in both (response to noradrenaline and isoprena- matched normal subjects. The minimum normal controls and IBS patients, and also line) and activation of neural elements basal pressure in RP (9±t)05 cm H.O, reduce the hypersensitivity of the rectum in (response to electrical field stimulation mean± SEM; p<0(001), AMP (18±3 cm IBS. [EFSI and dimethylphenylpiperazinium H.O; p<0.02), and SRU (20±2 cm H,O; [DMPP1). Electron microscopy (EM) was p<0.05) were all significantly lower than in carried out on each specimen. Seven normal subjects (28±6 cm H.O). The patients undergoing rectal excision were A histopathological study of severe constipa- squeeze pressure was significantly lower used as controls. in RP (52+3 cm H2O; p<0(02), AMP tion Pudendal neuropathy was present in all (58+7 cm H.O; p Effect of nicardipine on anorectal function in ganglionosis (one), and 'constipated' (14). M A KAMM, P R HAWLEY, AND J E LENNARD- on September 26, 2021 by guest. Protected copyright. normal controls and IBS patients There was close correlation between the JONES (St Mark's Hospital, City Road, two methods for recognising abnormal London) Patients with severe constipation W M SUN, A EDWARI)S, AND N W READ (Sub- colonic innervation. Four of the seven often do not 'relax' their pelvic floor during Dept of Huiman Gastroinitestinal Physiology patients, however, with a normal histo- defecation. Lateral division of the and Nutritioni, K Floor, Royal Hallamshire chemical appearance (all slow colonic puborectalis and upper external sphincter Hospital, Sheffield) Nicardipine is a calcium transit) had abnormal neurofilament 'stain- muscles was performed in an attempt to antagonist, which reduces smooth muscle ing'. The histopathological appearance at restore defecatory function in a group of contractility by inhibiting the entry of the resection margin related to the clinical these severely constipated patients. calcium into cells. A randomised double outcome. The combined use of these two The operation was carried out in 18 blind study was carried out on 18 patients techniques on resection specimens from patients, all women. Mean age was 32. with irritable bowel syndrome (IBS) and on patients with chronic constipation identifies Patients with Hirschprung's disease and 1() normal controls to compare the effect of more subtle abnormalities of colorectal secondary causes of constipation were a single dose (20 mg daily) of nicardipine on innervation than routine histological excluded. Fifteen patients had severe idio- subject's sensations and pressure responses methods. pathic constipation with normal barium on the anorectum to serial inflation of a enema, and three patients had a mega- rectal balloon with increasing volume of air rectum or megarectum and sigmoid. The and to ingestion of fatty meal. In normal operation was performed unilaterally in 12 controls, nicardipine significantly reduced Internal anal sphincter (IAS) function in and bilaterally in six; three patients had the the postprandial rate of rectal contractions, neurogenic faecal incontinence operation performed twice (on the same though it had no significant effect on the side). anal and rectal responses to rectal disten- R J NICHOLLS, D Z lUBOWSKI, D E BURL1EIGH, Three patients reported symptomatic sion with volumes of up to 200 ml. The AND M SWASH (St Mark's Hospital, City improvement (one bilateral, two unilateral Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1365 division). Improvement did not correlate The normal colon is therefore capable of defunctioning efficiency of the loop with a change in the EMG activity or generating high pressure peristaltic waves ileostomy was assessed in 23 patients. Six balloon expulsion. which correlate with effective transport patients experienced episodes of defecation The operation did not alter the mean of colonic contents. There was a clearly but only three had signs of stomal retrac- stated interval of 11 days between bowel definable abnormality in all the patients. tion. actions. Two patients no longer required Assessment of colonic transit in response to The defunctioning efficiency was assessed laxatives postoperatively. Three patients a standard chemical stimulus enables the by a modified radio-isotope and dye tech- showed a change to puborectalis relaxation delineation of functionally abnormal nique. Efficiency was assessed in the supine on EMG postoperatively and four were able regions. position to maximise overflow (n=7) or to expel a balloon only after operation, but during unrestricted activity (n= 16). these changes did not correlate with The median defunctioning efficiency symptomatic improvement. Mean resting (MDE) in the absence of defecation was anal canal pressure was unaffected by Discrimination is not impaired by excision of 99-99°, (99-95-100-0) irrespective of body surgery, but the maximum squeeze pressure the anal transitional zone after restorative position. In three patients with defecation was significantly decreased from 89-7±12 1 proctocolectomy and ileo-anal anastomosis but no stomal retraction, the MDE was (mean±SEM) to 48-5±7-4 (p<0-01). Four 99-97% (99-97-1000-). Defecation con- patients had slight mucous incontinence as a M R B KEIGHIIEY AND M C WINSIET (The tinued despite split ileostomy formation and result of surgery, but none had major soil- General Hospital, Birmingham) The anal all three underwent proctocolectomy for ing. transition zone (ATZ) is richly innervated acute distal disease. In three patients with The operation produced symptomatic by sensory nerve endings and is often not defecation and stomal retraction, the MDE improvement in only three of 18 patients involved in ulcerative colitis. It has been was 84-7% (31.16-99-0). After stoma but there was no major morbidity. suggested that the ATZ should be pre- revision the MDE improved to 99-99% served in patients having restorative (p<0-0)1). In the absence of stomal retrac- proctocolectomy and ileoanal pouch tion, the loop ileostomy achieves almost anastomosis. We have studied eight complete defunction, regardless of whether Dynamic colonic scanning - defining the patients before and after ileoanal pouch the proximal limb is dependant, and con- regional defect in severe idiopathic constipa- anastomosis to determine the influence of tinued defecation is secondary to active tion excising the ATZ on anal sensation and distal disease. Defecation is only due to ability to discriminate gas from solid stool distal overflow if there can be associated M A KAMM, D G IHOMPSON, J E LENNARD- postoperatively. Anal sensation was stomal retraction and this is cured by stoma JONES, E WAI KER, 1 BINGIIAM, R SOBNACK, measured in the anal high pressure zone as revision. AND N W GARVIE (St Mark's Hospital, City defined by manometry using a unipolar Road, London ECI V 2PS and the London constant current stimulator. The median Hospital, Whitechapel, London) We have threshold sensation in the lower zone of the http://gut.bmj.com/ developed a technique which enables the anal canal postoperatively was 62 mA Factors influencing the outcome of restora- delineation of functionally abnormal compared with 134 mA postoperatively tive proctocolectomy colonic regions and applied it to patients (p<0-02). Mid zone and upper zone thres- with severe idiopathic constipation. hold values had a median of 67 mA and 77 MC WINSLET, R F1.INN, AND M R B KElGilil'Y Six healthy volunteers and seven patients mA preoperatively but sensation was (The General Hospital, Birminigham) were studied. A multilumen PVC tube was unrecordable (>150 mA) after restorative Factors influencing the outcome of restora- swallowed and its progress to the caecum proctocolectomy (p<0.0 1). Despite the tive proctocolectomy in 40) patients monitored by screening. 99mTc-DTPA was objective loss of sensation in the upper anal followed up for a median of 20 (6-46) on September 26, 2021 by guest. Protected copyright. injected into the right colon, followed by canal, only one of the eight patients was months has been assessed by univariate and bisacodyl solution, a powerful colonic unable to discriminate gas from semisolid multivariate analysis. The variables stimulant. Transit was monitored by gamma stools three months after operation, soiling assessed included age, sex (F=2 1), previous camera, and in four subjects proximal was reported in only one patient, none colectomy (n= 15), covering ileostomy colonic pressures were simultaneously were incontinent and all were able to (n=35), rectal cuff preservation (n= 13), recorded. defer defecation for more than one hour. endoanal mucosectomy (n= 15), type of In the controls bisacodyl caused high Although the excision of the ATZ impairs pouch (S-=, W=8, J=31), diagnosis pressure peristaltic waves associated with anal sensation, functional results do not (UC=30, polyp=3, megarectum =4, rapid transport of isotope to the rectum. appear to be impaired. Crohn's disease=3), vascular mobilisation Patients showed a spectrum of abnormal (n=20), experience (last 20 cases), and response, from slow transit involving the complications: pelvic sepsis (n=12), anal whole colon to slow transit involving the left stenosis (n=9), fistula (n=8), obstruction colon only. The range of hepatic flexure to Aetiology of continued 'defecation' in the (n=6). Failure was defined as pouch rectum transit time was 1-10 mins in the presence of loop ileostomy excision intubation or continued proximal controls, and in four patients was 14-25 stoma (n=9). The complication score (t)-8) mins while in three patients the isotope M C WINSLE'I', Z DROHL, A ALLAN, J included: bleeding, sepsis. stenosis, fistula did not reach the rectum by two hours ALEXANI)ER-WILLIAMS, AND M R B KEIGHLEY and obstruction. The functional score (p<0-01). In addition to delayed movement (General Hospital, Birmingham) A loop (0-12) assessed frequency, use of pads, of the 'isotope head', patients demonstrated ileostomy is the defunctioning procedure of urgency, soiling, incontinence, discrimina- impaired transport of the bulk of the isotope choice but may not guarantee complete tion, use of anti-diarrhoeals and dietary mass. defunction. To evaluate this criticism the restriction. Failure occurred in two patients Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1366 The British Society ofGastroenterology with Crohn's disease and seven with ulcera- H R JENKINS, U SCIINACKENBERG, AND P J days with an elemental diet (Ensure, 1500 tive colitis and was significantly more MILLA (Institute of Child Health, London) A KCal/d) supplemented by Golytely 2 L/d in common after endo-anal mucosectomy major function of the colon is the conserva- one patient and activated charcoal 20 g/d in (53% v 4%, p<0).01), rectal cuff preserva- tion of salt and water which may be aided by the other patient resulted in persistently low tion (46% v 11l o, p<0)(5), and pelvic sepsis short chain fatty acids. The only previous breath H2 with a mean of 13 ppm (3-38) (37% v 4%, p<0.01). The complication studies of the mechanisms involved in and 12 ppm (5-21) as shown on daily breath score was only increased after endoanal infants have been in vivo where electrical H2 monitoring. Symptoms improved and mucosectomy (3 v 0, p<0(05). Only pelvic gradients influence ionic movements. We sequential plain abdominal films showed sepsis (10 v 1, p<0.01) and fistulae (10 v 1, have carried out a more detailed study of virtually complete regression of cysts. p<0.05) influenced the functional score. transport in isolated human infant colon This well tolerated treatment resulted in a Hospital stay was significantly prolonged using a Ussing Chamber and voltage clamp marked reduction of H2 production prob- after preserving the rectal cuff (39 v 23 days, procedure. Stripped L side colonic mucosa ably by depriving H2 producing bacteria of p<0.05), endoanal mucosectomy (40 v 23 (n=6 pairs) was mounted and bathed in substrate. We assume that this reverses days, p<0.01), pelvic sepsis (48 v 23 days, Krebs solution. Under short circuit con- concentration gradients from cyst to bowel p<0.01), and fistulae (49 v 24 days, ditions Nat (3-45±1 53 [lmol/h/cm2 mean resulting in disappearance of the cysts. p<0.05). 1 SD) and Cl ((0-63±3.61) were absorbed and a residual ion flux consistent with Segmental colonic transit in ulcerative colitis HCO3 secretion approximates Cl absorp- - effect of Asian versus Caucasian diet tion. Short circuit current (3-8±0+28) COIORECTAI 11 approximates net Na' movement. Sixty millimoles acetate increased Na' absorp- Colonic cellular proliferation rates in R C SPILl.ER, H H TAY, D B A SILK, AND J J MISIEWICZ (Department of Gastro- tion (3-45+ 153 to 7-74±2-25, p<0(05) by a normal subjects: the effect of the faecal enterology, Central Middlesex Hospital, large increase in mucosa to serosa flux stream Acton Lane, London) Recent reports that (7 24±0 92 to 13 55±1 62, p<0.01). The increased net absorption of Na+ was M WINSIET, A Al LAN, DENISE YOUNGS, AND proctitis is associated with delayed colonic ' transit have not allowed for the known markedly reduced by 10 M amiloride M R B KEIGHLEY (The General Hospital, effect of dietary fibre. In the present study (7.74±2.25 to 1-75±1 72, p<0.01) which Birmingham) The role of the faecal stream segmental colonic transit, three day stool was also associated with a marked reduction in maintaining colonic mucosal cellular weights and fibre intake have been assessed in tissue conductance. These data clearly kinetics was assessed by measuring the cell in 26 patients, 14 with proctitis, 11 with show that in the infant Na+ is absorbed birth rate (crypt cell production rate - proctocolitis. Ten were taking an Asian and electrogenically and C1 electroneutrally in CCPR) of normal rectal mucosa in 10 exchange for HCO3 unlike in vivo where patients undergoing faecal diversion by 16 a Caucasian diet. There was no differ- http://gut.bmj.com/ ence between the two diet groups in sex Cl moves according to the electrical ileostomy for incontinence (n=6) or protec- ratio or disease distribution and activity as gradient. Short chain fatty acids favourably tion of an anastomosis (n=4). Rectal assessed endoscopically. Twenty radio- influence Na+ salvage and do so via the biopsies were obtained before diversion and opaque pellets were ingested at 900 am on amiloride sensitive Na' channel. Thus two, six, and 12 weeks afterwards. The days 1-3. Mean transit in hours was 1 2 x the bacterial metabolism of carbohydrate in the effect of restoration of intestinal continuity number of pellets seen within each segment infant colon may be important in the con- was assessed at the same time points in nine on a radiograph taken at 9 00 am on day 4. servation of salt and water. patients undergoing closure of ileostomy Patients taking a traditional Asian diet (post incontinence procedure n=4, post had larger stool weights, 278±19 g/24 h, anastomotic protection n=5) CCPR was on September 26, 2021 by guest. Protected copyright. (mean±SEM) n= 10, compared with those assessed by an in vitro stathmokinetic Breath hydrogen monitoring in Pneumatosis method with vincristine induced metaphase taking a Western diet, 160±24 g, n=16, coli p<0-01. Total colonic transit was corres- arrest. Faecal diversion was associated with pondingly faster (12+6 v 32+3 h, p<0)01), a significant fall in CCPR from 3-4±1-0 M SCHLUP, G 0 BARBEZAT, AND V S CHADWICK prediversion to 1-2±0-4 at two weeks, correlating inversely with stool weight, (Department of Medicine and Wellcome r=0-56, p<0O1. The difference in fibre p<0 05. The CCPR subsequently increased Institute, University of Otago, Dunedin, to 1 7±0+4 at six weeks, and 3-3±1 5 at 12 intake (28±4 v 20±2 g) was not significant New Zealand) Intestinal gas producing suggesting that other factors- for example, weeks. Restoration of intestinal continuity bacteria have been implicated in the patho- was not associated with a significant change spices are responsible for the accelerated genesis of Pneumatosis coli. Previous colonic transit. The extent of disease per se in CCPR. Faecal diversion causes a signifi- reports of high hydrogen (H2) content cant transient reduction in rectal CCPR. did not influence transit. The difference in within cysts and breath of some patients transit between active (12-6±3.2 h, These data suggest that the faecal stream n=10) prompted us to investigate two female has a tropic effect on mucosal cellular and inactive disease (31±4 h, n=20) was, patients (aged 57 and 47 years) with colonic however, not significant. Thus in our proliferation. The mechanism of this pneumatosis coli presenting with tenesmus phenomenon is unclear. patients diet appears to have a more power- and rectal bleeding. In both patients mean ful influence on colonic transit than their fasting breath H2 concentrations were disease. raised: 75 ppm (range 65-87) and 49 ppm Effect of dietary fibre supplementation on (41-54). A bowel lavage (Golytely, 4 L in colonic pH in healthy volunteers Mechanisms of transport of sodium and four hours) reduced breath H2 from 65 ppm chloride and the effects of short chain fatty to 15 ppm and from 42 ppm to 1() ppm within G PYE, J CROMPTON, D F EVANS, A G CLARKE, acids in the human infant colon 12 hours. Subsequent treatment for seven AND J D HARDCASTILE (Department of Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A1367 Surgery, University Hospital, Nottingham) patients subsequently had colonoscopic malignancy is still subject to debate. One There is evidence of suggest that intra- polypectomy. On average after admission factor which may influence the outcome is luminal pH<6-5 may inhibit the formation positive scans were performed earlier 4-3 the presence of vascular or lymphatic of carcinogens and hence be protective days (range 0-5-14 days) than negative invasion. against colorectal cancer. The capacity of scans 6-7 days (range 1-14 days). We have examined the clinical and histo- fibre to lower luminal pH may, therefore, W'Technetium scintigraphy is a useful logical features in 7t) malignant polyps be of significance in preventing colonic procedure and has a high diagnostic yield. It removed at colonoscopy. Thirty six were malignancy. allows preoperative identification of bleed- judged to have carcinoma in situ, of which The ability of dietary fibre supplementa- ing sites and should be used early when 35 had no further therapy. One had an tion to acidify the colon has been studied in bleeding is still occurring. anterior resection with no evidence of eight healthy volunteers. Gastrointestinal malignancy. There were no polyp related pH was measured using a pH sensitive deaths during follow up (24-48 months). Of radiotelemetry capsule and portable Left sided colonoscopy as screening pro- the 34 who had invasive carcinoma, 15 were recording equipment. Subjects were cedure for colorectal neoplasia in asympto- judged to have had incomplete removal studied twice before dietary supplementa- matic volunteers >45 years either endoscopically or histologically, all tion, twice during the four week period of had surgery - seven had no evidence of supplementation of 30 g/day with isphagula D P FOI FY, P DUNNE, M O BRIEN, J CROWE, T W tumour, all alive and well (12-55 months). husk (Fybogel) and once afterwards. O'CALLAGHAN, AND J R LENNON (Louth Eight had tumour present: six Dukes' A There was a significant reduction in mean Hospital, Dundalk, Depts of Gastroenter- alive and well (24-48 months). One Dukes' colonic pH in both the right and left sides of ology and Pathology, Mater Misericordiae B, died 10 months and one Dukes' C alive the colon (6-5 to 5-8, p<0-001; 7-3 to 6-6, Hospital, Dublin) Screening colonoscopy to 36 months. p<0-01) after Fybogel compared with con- splenic flexure (left sided colonoscopy) was Nineteen were judged to have had com- trol values. A reduction in the percentage of offered to 738 asymptomatic volunteers plete excision and 17 had no further treat- time with pH>6-5 was also observed (52% >45 years in an area with high mortality ment. Thirteen alive and well (12-56 to 21% right; 78% to 54% left). Colonic pH rate for colorectal carcinoma. Five hundred months) two had surgery. Both had residual had returned to near normal within two were accepted and examined without pre- tumour with evidence of vascular invasion. weeks of cessation of dietary supplementa- medication by an Olympus 100 cm colono- These results suggest that invasive tion. scope after preparation by Fletchers enema. carcinoma can be treated by polypectomy This study shows that isphagula husk can Splenic flexure was reached in 435 patients, only if vascular invasion is excluded. If in significantly acidify both right and left colon descending colon in 49 with average doubt laparotomy is indicated. and that these effects are short lived. duration of examination eight minutes. Examination failed in 16 patients. All http://gut.bmj.com/ polyps were biopsied and if adenomatous or Juvenile polyposis - a precancerous condi- Role of in vivo "'technetium labelled red >5 mm subsequent full colonoscopy/ tion blood cell scintigraphy in lower gastro- polypectomy was done. Of 180 patients with three had 86 intestinal haemorrhage polyps, carcinoma, adenoma, J R JASS, C B WILLIAMS, B C MORSON, AND H1 J R 45 hyperplastic and 35 had miscellaneous BUSSEY (St Mark's Hospital, City Road, lesions. The adenoma group 64 J F SHARP, J P NEOPTOLFMOS, M NICHOLSON, comprised London) Juvenile polyposis coli is inherited E M WATKIN, AND D P FOSSARD (Departments men (prevalence 20%) and 22 women (pre- as an autosomal dominant condition and valence had of Surgery and Radiology, Leicester Royal 12%). Thirty patients (35%) colorectal polyps number between 5-300. on September 26, 2021 by guest. Protected copyright. Infirmary and Leicester General Hospital, more than one adenoma and 14 (16%) had Patients usually present in the second Leicester) Twenty eight patients with major adenomas >1 cm. Full colonoscopy in 94 decade with profuse rectal bleeding. rectal bleeding had in vivo 'mtechnetium patients showed adenomas proximal to Although the juvenile polyp is a pertechnetate (395-590 mBQ) labelled red splenic flexure in nine. hamartoma, associated colorectal malig- cell scintigraphy in an attempt to identify Our study shows that of 500 asympto- nancy has been described. the haemorrhage site. Serial scans (0-35 matic volunteers >45 years, 0-6% had One thousand and twenty five polyps hours) were taken using a large field gamma malignant and 17-2% potentially malignant from 85 patients with juvenile polyposis camera (106 counts). lesions in the left colon. The procedure, left have been examined. Eight hundred and Three patients were children. There were sided colonoscopy, was acceptable (compli- thirty four were typical juvenile polyps; 7t) 17 male and eight female adults, mean age ance 68%) and well tolerated. (8%) showed mild and six (1%) showed 72-4 years (range 51-91 years). The average moderate dysplasia. None showed severe haemoglobin at presentation was 9-5 g/dl dysplasia. One hundred and sixty eight were (range 5-4-13-5 g/dl). The mean transfusion Colonoscopic management of malignant designated as atypical juvenile polyps. was 8-2 units (range 3-20). polyps - an audit These were multilobated or papillary and Twenty nine scans were performed; 22 comprised relatively more epithelium and were positive and in all these the site of I M CHESNER, S MULLER, M EGAN, J NEWMAN, less stroma than the typical variety. Fifty haemorrhage was identified either during AND E T SWARBRICK (East Birmingham (30%) showed mild, 25 (15%) moderate the episode of bleeding (n=14) or subse- Hospital, Selly Oak Hospital, Birmingham and three (2%) severe dysplasia. The quently (n=8). The bleeding site was con- and Newcross Hospital, Wolverhampton) remaining polyps included 21 adenomas firmed by colonoscopy, arteriography or at Colonic polypectomy is now accepted and two hyperplastic polyps. Sixteen laparotomy. Seven patients had negative management for polyps, however, its role in patients had a colorectal cancer. Two scans, no bleeding sites were found but two the management of polyps with invasive cancers were confined to the head of a Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1368 The British Society ofGastroenterology polyp, one being a typical juvenile polyp phases of the cell cycle (GI, G2, S and M). In four patients the total tumour volume showing mild dysplasia and the other a We used a monoclonal antibody to K1-67 was assessed before and after treatment, the villous adenoma showing severe dysplasia. and an immunohistochemical assay to study volume removed was 5-1±2 cc (3-4 treat- The mean age of patients with cancer was 34 cell kinetics in fresh frozen sections of ment sites each session). One tumour could years (range 15-59). normal colon (12), colonic carcinomas (30) not be detected endoscopically, endosono- It is concluded that juvenile polyposis is a and colonic adenomas (27). The K 1-67 graphically, or on biopsy after treatment rare but important precancerous condition score represented the percentage epithelial (follow up five months). One patient with a and that affected patients require careful cell nuclei which stained positively. large tumour required two units of blood surveillance and genetic counselling. The K1-67 score ranged f'rom 30 to 95 two days after the second treatment. Photo- (mean 58) in carcinomas, 24-78 (mean 47) dynamic therapy is a promising method of in adenomas, and one to 20 (mean 7-8) in treatment for small colorectal cancers. Desmosomes and human colorectal cancer normal colons. The K1-67 positivity in the normal colons was confined to the lower third to half of the crypt. contrast J E MARSTON, D R GARROI), F P PARRISH, ANI) By Anal leukoplakia I TAYILOR (University Surgical Unit, South- adenomas showed positivity throughout ampton General Hospital, Southampton) including the surface epithelium. Wide- D R DONALTDSON, J R JASS, AND C V MANN (St Reduced adhesion between malignant cells spread staining was also noted in Mark s Hospital, City Road, London) Anal may result in some becoming dislodged, carcinomas. leukoplakia is a rare and ill understood thus contributing to metastases. Desmo- No correlation was noted between K 1-67 condition. The clinical findings and path- somes are adhesive intercellular junctions score, histologic architecture and degree ology of 27 patients have been reviewed in between epithelial cells. The presence and of dysplasia in adenomas and similarly no order to assess the results of treatment and distribution of desmosomes in 47 primary correlation was noted between the histo- the association of' the condition with anal colorectal cancers, eight peritoneal recur- logic grade or dukes staging in carcinomas. cancer. rences, and six liver metastases were The study of cell kinetics using KI-67 Patients presented with pruritus or an studied using fluorescent staining with immunostaining in tissue sections provides anal lump. Ages ranged from 31-79 (mean antidesmosomal antibody. Desmosomes new insights to the evolution of colonic 60 years) and the M:F ratio was 20:7. were present in all tumours investigated, adenomas and adenocarcinomas. Examination revealed hard, granular white including metastases. In moderately well plaques surrounded by moist, thickened differentiated tumours the distribution perianal skin. The lesion was either well was identical to uninvolved mucosa. The Photodynamic therapy (PDT) for colorectal circumscribed or circumferential. The fluorescence was confined to opposing cancer histological findings were characterised by lateral membranes, being intense in the hyperkeratosis, acanthosis, 'spiky' down- http://gut.bmj.com/ subapical regions and reduced towards the H BARR, S G, BOWN, ANI) N KRASNER (Th1e growth of rete ridges and a band-like bases of the cells. In poorly differentiated Gastrointestinal Unit, Walton Hospital, chronic inflammatory cell infiltrate at the tumours cell polarity was lost and desmoso- Liverpool and The National Medical Laser dermo-epidermal junction. There was a mal staining was evenly distributed around Centre, Dept of Surgery, University College, synchronous keratinising squamous cell the cells. The desmosomal distribution in London) Photodynamic therapy is a tech- carcinoma in nine patients (M:F=5:4, mean primary tumours and metastases was nique for local tissue destruction with light age 57 years) which was usually well essentially similar. after prior drug sensitisation which has differcntiated. A tenth patient (female) The stability of desmosomal junctions to selectivity for malignant tumours. Animal developed a perianal squamous cell on September 26, 2021 by guest. Protected copyright. reduced extracellular calcium was also experimental studies show that colonic carcinoma I1 years after the diagnosis of studied. In normal epithelium, junctions tumours necrose and slough whereas leukoplakia - the patient having defaulted remained intact for at least 1-5 hours: normal colon heals by regeneration without from follow up for four years. Patients with between malignant cells, not only desmo- risk of perforation. We treated eight and without cancer were treated by surgical somes but entire cell contacts were dis- patients (four men, four women) aged excision±skin flaps or grafts, but leuko- rupted within 30 minutes and resulted in 43-88 years with colorectal cancers, inoper- plakia recurred in the majority of cases, release of viable cell clumps. This differen- able because of metastases (four), severe often repeatedly. This study has shown that tial adhesiveness of tumour cells in vitro cardic disease (three), or refusal of surgery anal leukoplakia is frequently associated may be of significance in understanding the (one). Five were below the peritoneal with squamous cell carcinoma and the con- development of colorectal metastases. reflection (6-13 cm from anus) and three dition recurs despite recourse to aggressive above (18-31 cm). Each was photosensi- surgery. Patients need careful follow up and tised with 2-5 mg/kg haematoporphyrin current surgical therapy requires re- Immunohistochemical analysis ofcell kinetic derivative (HpD) iv and treated two and evaluation. parameters in colonic adenocarcinomas, eight days later with 630 nm red light from a adenomas, and normal colons dye laser, delivered via a 0-4 mm fibre passed through a colonoscope and inserted Intraoperative pelvic cytology accurately P JOHNSTON, M O BRIEN, P D)ERVAN, J CROWE, 1-5 mm into the tumour. Total energy at predicts those at risk of developing local J l,ENNON, AND D N CARNEY (Departments each site was 50 J. The depth of invasion, recurrence of colorectal cancer of Gastroenterology, Pathology and assessed by endosonography in six patients Oncology, Mater Misericordiae Hospital, ranged from 0(7-3-2 cm. The mean depth of CHRISTINE HAIL, S H SIlVERMAN, JANET Dublin) The K1-67 antigen is a nuclear tumour removed at each treatment site was MOORE, H TJHOMPSON, AND M R B KEIGHLEY antigen expressed in the proliferative 0-54±0-28 cm (one week after treatment). (The General Hospital, Birmingham) Much Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 1369) attention is currently being paid to the tion will allow accurate diagnosis and per- prospective survey of the indications lor importance of lateral clearance during mit a more rational treatment plan to he endoscopy, findings, and consequential operation for colorectal cancer in order to adopted. changes in management which hatve occur- prevent local pelvic recurrence. We have red as a result of upper G1 endoscopy in this examined 50 patients using intraoperative group of patients. cytology to detect residual pelvic disease Fistulae in anorectal sepsis: the relevance of Approximately 30 HIlVah patients cur- and report the correlation between positive microbiology and necessity of repeat exami- rently aittend the genitourinarv medicine cytology and the incidence of local recur- nation under anaesthesia clinic of whom 50 have AIDS. A turther I Il rence. The first 25 patients were examined AIDS patients have previously been by imprint cytology of tumour bed biopsies M C WINSILET, N S AMBROSE, AND A ALLAN treated, and 36 subjects have beeii end(lo- which were then submitted for histological (Selly Oak, General and Queeni Elizabeth scoped. (19 AIDS). The indications for examination. The second 25 patients were Hospitals, Birmingham) Isolation of colonic endoscopy were x-ray negative dyspepsil studied by scrape cytology of the four aerobes (CA) or 'gut specific' bacteroides (16), abnormal barium swallow/meal ( I I), quadrants of the pelvis and histology was (GSB) from anorectal pus is reported to be intractable dysphagia ( 10), Lupper gastro- considered positive if there was tumour indicative of a fistula, and in the absence of a intestinal bleeding (four). Abnormalities present in the perirectal fat. Eleven of the demonstrable fistula is a specific indication were found in 14/17 HIlVab cases, (82'%), 50 patients had positive cytology. Two died for repeat examination under anaesthetic (x--ray negative dyspepsia 7/9, intractable in the immediate postoperative period; (EUA) to reduce recurrence. To confirm dysphagia 4/4, abnormal harium meal 3/5). there were five local recurrences in the these proposals a retrospective review of The findings in eight HIVab patients (47(%). remainder at a median follow up of 20 103 patients with cultured anorectal pus was resulted in the diagnosis of AID)S; (four months. Of the 39 negative patients, nine performed: perianal abscess=65, ischio- Kaposi's sarcoma (KS), two oesophageal were considered positive on histological rectal abscess=38. Incision and drainage cytomegalo virus (CMV) ulceration, one criteria, with one local recurrence. There (I&D) was performed in 67 patients, and gastric lymphomra, one oesophageal tuber- were four local recurrences in the 30 combined with EUA in only 36. A fistula culosis). The remaining six patients hiad patients negative on both criteria, a highly was demonstrated perioperatively in seven oesophageal candidiasis. significant difference (0.5>p>0(25 X2). We patients (I&D=4, EUA=3) and in 11 at Endoscopic and histologicall confirmiationl conclude that intraoperative cytology pre- follow up (I&D=10, EUA=1), median of suspected gastrointestinal KS was dicts those at risk of developing local pelvic three (1-36) months. CA/GSB were iso- obtained in five AIDS patienits, and the recurrence. It is more important to detect lated in 71 patients (68-90%). Only 12 of 18 remaining 14 subjects had oesophageal malignant disease remaining in the patient patients with a fistula had CA/GSB present. ciandidiasis (six), bleeding peptic ulcer than that removed with the histological Of 59 patients (83%) with CA/GSB but no (three), oesophageal CMV (two). alnd specimen. overt fistula only eight required further normal examination (three). surgery, with 51 (71-8%) requiring no We conclude that a high diiagnostic yield http://gut.bmj.com/ further treatment, median follow up two is obtained at endoscopy in AID)S and (2-4) years. Isolation of CA/GSB is sugges- HiVab subjects with upper gastrointestinal tive but not diagnostic of a fistula. An initial symptoms, leading to changes in mianaige- Endoluminal ultrasound in benign anorectal EUA should be performed to exclude a ment in more than 50," of patients disease fistula but irrespective of the culture a examined. second EUA is not indicated as most A DOBI.F AND A J W SIM (St Mary's Hospital, patients remain asymptomatic. Occult London) The role of endoluminal ultra- fistulae are not responsible for the high on September 26, 2021 by guest. Protected copyright. sonography in the management of rectal incidence of recurrent sepsis. Experience with small bowel endoscopy in carcinoma is well established. This tech- Kuwait nique has not, however, been evaluated in benign ano rectal disease. Sixteen patients BASIL Al.-NAKIB, S RAI)IIAKRISIINAN, ILABIBA with a variety of benign anorectal diseases IAMIN, S M All, ANI) Y 0MFR (Al-Ainiri have been studied with the Bruel and Kjaer Teaching Hospital, Ku wait anid Kuwait 1846 type ultrasound scanner. The sites of EN DOSCOPY (ancer Control Centre, Ku wait) Endo- eight abscesses, three ischiorectal, three scopic examination of' the small bowel intersphincteric and two extrasphincteric, Diagnostic yield of upper gastrointestinal beyond the ligament of Treitz's is done and a fistula-in-ano were correctly demon- endoscopy in human immunodeficiency rarely, because of the relative infrequency strated. Three solitary rectal ulcers were virus antibody positive patients of small bowel disease and lack of a suitable shown to be mucosal lesions, as was a equipment. Over a two year period, we benign tubulovillous adenoma. Muscular I G BARRISON, S M FOSTER, J R W HARRIS, A J have done 180 such endoscopic examina- defects were seen in one patient with a PINCHING, AND J G WALKFR (Departments of tions in 120 patients. A pediatric colono- complete anal sphincter division, in two Gastroenterology, Genito- Urinary Medicine scope (Olympus PCF) was used als a jejuno- patients with colorectal anastamotic defects and Clinical Immunology, St Mary's scope by the push type method, and the and by study of in vitro sphincter division in Hospital and Medical School, London) jejunum up to 60 cm from the duodeno- an abdomino-perineal resection specimen. There is considerable concern about the jejunal flexure was exatmined with target The results of this pilot study clearly show risks of endoscopy in human immunode- biopsies. Abnormalities were present in 81 the capability of endoluminal ultrasono- ficiency virus antibody positive (HiVab) (69%) patients. In the 19 patients who had graphy in defining the pathological anatomy patients and some doubts about the diag- immunoproliferative small intestinal disease of benign anorectal conditions. Such defini- nostic yield. We report the results of a (IPSID), four endoscopic groups could he Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1370 The British Society of Gastroenterology described. Among the 17 patients who had bouginage of oesophageal stricture (four). one hour after colonoscopy were scored for subtotal villous atrophy, the mucosa looked Results were uniformly satisfactory. In gaseous distension and operator question- almost normal endoscopically in the child- particular, we have found that stricture naire evaluated adequacy of procedure and ren, while oedema, diffuse nodularity and management was markedly improved by technical difficulty. ulcerations as seen in IPSID was observed the use of the new technique of balloon During colonoscopy mean pain score of in three adults. A large jejunal polyp was dilatation. We had no morbidity. 1-7 for air and 1-8 for CO, were similar. At found to be the source of an obscure gastro- six and 24 hours, gas passed with air was intestinal bleeding. In addition, six patients greater (p<0()01). At six hours pain score who had duodenojejunal Crohn's disease, Gastric vascular ectasia: nine cases and was 0 and 0)8 (p<0-001 ) and at 24 hours was two with schistosomal jejunitis, and one treatment by laser photocoagulation 0) and ()-7 (p<)-0)( 1) for CO, and air respect- with Henoch-Schonlein purpura were diag- ively. Forty five radiographs were evaluated nosed by jejunoscopy and histology. Thus J E COXON AND D F BEC[KILY (Plymotuth in five categories- 16 of 17 with CO, in the direct examination of the mucosa with biop- G(eneral Hospital, Plymouth, Devon) first three (no gas to slight excess) and 28 of sies was of significant value in our region, Gastric vascular ectasia (watermelon 28 (p<0-001) with air in the last two where a variety of small bowel pathology stomach) is a cause of chronic severe upper (moderate to severe excess). There was no exist. gastrointestinal blood loss. The condition is difference in operator evaluation for air or rare with only 17 previously recorded cases. COl. We present nine further cases and suggest: Insufflation with CO, causes less pain to (1) The condition may be more common patients and no extra difficulty to endo- Paediatric upper GI endoscopy - an experi- scopists. We recommend its routine use in ence of 531 cases than supposed. In four of our cases the typical appearances were described at colonoscopy. P K H TAM (INTRODUCED BY PROFESSOR R a previous endoscopy but the condition SHIELDS) (Division of Paediatric Surgery, was not recognised by the endoscopist. Department of Surgery, University of Hong (2) There may be an association with A study of intracolonic hydrogen and Kong, Queen Mary Hospital, Hong Kong, pernicious anaemia. Three of our cases methane concentrations in patients present address: Department of Child were receiving B12. The median B12 of the Health, Alder Hey Children's Hospital, other cases was only 202 (range 163-256). J CROWE, J LENNON, AND E A (GAiI.AGHFER Eaton Road, Liverpool) Reports on the use All but one of the patients had a microcytic (Gastrointestinal Uniit, Mater Misericordiac of flexible GI endoscopy in the paediatric anaemia at the time of diagnosis but of five Hospital, Dublin, Ireland) Samples of intra- population have been scarce. Our experi- patients who had a previous unrelated colonic gas were obtained during routine ence of 531 examinations on 364 children admission, four had had an MCV greater colonoscopy from three groups of patients- (age range 1 month-16 years) in the past 12 than 95. One patient had antiparietal cell namely, polyethylene glycol (PEG) (n=23, http://gut.bmj.com/ years represents one of the largest series antibodies. (3) The treatment of choice is a samples=38), phosphate enemia (n=34, available and illustrates the advantages of distal gastrectomy, performed successfully samples =41) aind mainnitol (n =4, samples= having such a service in a regional centre. in two of our patients. Four patients refused 8). Chromatograph analysis was done on The vast majority of our procedures did or were not fit for surgery and in three of each sample for nitrogen, oxygen, methane, not require anaesthesia. Indications these patients the condition was treated by hydrogen, carbon dioxide and water. Air included upper GI bleeding (99), abdomi- laser photocoagulation of the affected insufflation was used during each pro- nal pain (168), foreign body ingestion (76), portion of the stomach using a NdYAG cedure. In the PEG group, potentially vomiting (10), dysphagia (5), reassessment laser. Blood loss measured with Cr5' label- explosive concentrations occurred in six of on September 26, 2021 by guest. Protected copyright. (149), miscellaneous (24). Findings were led red cells in ml/day was significantly 38 samples. 1-10% relative concentration. chronic peptic ulcer (47), gastroduodenitis reduced by photocoagulation (before 140, In the phosphate enema group, four of 41 (59), neoplasm (5), foreign body impaction 80, 72-5; after 0)4, 0-56, 1-85). gas samples had 1-1(0% relative concentra- (19), varices (7), stricture (4), normal (201), tion and in the mannitol group two of eight recurrent disease (32), healing pathology samples. No sample had potentially explo- (114), miscellaneous (59). GI bleeding had CO2 v air - an evaluation of discomfort after sive concentrations of methane. All prep- the highest diagnostic yield (84.8%0). colonoscopy arations were judged to be good by the Routine endoscopic assessment of response endoscopist. All patients had a coexisting to ulcer therapy was valuable in detecting J A WIlSON, i, J IRVINE, R (GOODACRE, J oxygen concentration of 50/O or more, recurrence (27/47) and guiding treatment. O'CONNOR, AND G STE,VENSON (Divisions of necessary for combustion of hydrogen or The only pitfall associated with flexible Gastroenterology an1d Radiology, McMaster methane in their explosive ranges. endoscopy was the failure of detection of University, Hamiltoni, Ontario, C'aniada) These results show that pockets of gas recurrent tracheo-oesophageal fistulas in Much of the discomfort after colonoscopy is containing potentially explosive concentra- two infants. In this age group, the available caused by air insufflated endoscopically. tions of hydrogen may occur in the colon endoscopes are still not optimal for this Carbon dioxide (CO,) is absorbed more after preparation with PEG, mannitol or purpose. ERCP was successfully performed rapidly than air from the colon and may phosphate enema, and that carbon dioxide in 11 children with biliary and pancreatic cause less pain. Fifty six patients under- (an inert gas) insufflation should always be problems and gave useful anatomical infor- going colonoscopy were randomised in used if diathermy is to be used. mation to guide management. double blind fashion to insufflation with air Therapeutic procedures (55) included or CO. Symptoms were evaluated by injection sclerotherapy (32), foreign body questionnaire at one, six, and 24 hours after Radial pressures during stricture dilatation removal (19), and endoscopic-guided colonoscopy. Abdominal radiographs taken with bougies and balloons Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A1371 J G C COX, G K BUCKTON, AND J R BENNErr complications (11-3%) including five with 1 M DIAS, S R CAIRNS, P R SALIMON, AND P B (Hull Royal Infirmary, Anlaby Road, Hull) empyema (4.7%0). Analysis of clinical, COTTON (Department of gastroenterology, It has been suggested that balloon dilatation haematological and biochemical factors The Middlesex Hospital, London) During a of oesophageal strictures may be gentler together with ERCP findings revealed pre- three year period to February 1987, 624 than bougienage, and that less force is existing cholangitis to be the only factor of patients underwent successful endoscopic needed. To assess this pressure recordings any value in predicting gall bladder sphincterotomy for common bile duct were done during bougie dilatation in eight complications. (CBD) stones. Ninety of these patients had patients with benign oesophageal stricture These results suggest that an active policy incomplete duct clearance at the first (mean stricture diameter 7-25 mm). Initial of CBD stone clearance should be followed attempt, principally because of the stone dilatation was carried out with Celestin and that clearance should be confirmed as size, and had one or more endoscopic dilators. The dilatation was completed with far as possible. Mortality from post-ES prosthesis (EP) inserted into the CBD. a size 58 Fr Eder-Puestow bougie specially complications might be further reduced by There were two procedure related deaths, modified with a side hole catheter use of other non-operative interventional one limited postsphincterotomy haemorr- implanted at its waist, connected to a techniques. hage and one failed stent insertion. pressure transducer; pressure recordings Follow up of 31 patients (mean age 71 1 were made throughout the dilatation. The years) given EP as a temporary measure was pressures measured were the final dilating Endoscopic management of large (>2 cm) up to 3-1 months (mean 2-5). All patients pressures for each dilatation. The results CBD stone associated with recurrent subsequently had complete duct clearance, showed that in five out of eight patients this pyogenic cholangitis 19 endoscopic and 12 at laparotomy. There pressure exceeded 49 kPa (370 mm Hg) and were no deaths. Twenty five patients (mean in the three other patients was an average of J WC LEUNG, SC S CHUNG, S D MOK, ANI) A K C age 83-8 years) considered unsuitable for 31 kPa (230 mm Hg). Li (Combined Endoscopy Unit, Prince of further endoscopic or surgical therapy In 45 strictures (mean diameter 7-6 mm) Wales Hospital, The Chinese University of were given EP as definitive treatment and dilated by a 20) mm balloon, the final dilating Hong Kong, Hong Kong) The technical followed-up to 37-9 months (mean 18-1). pressure was up to 151 kPa (1133 mm Hg) in difficulty and risk involved with endoscopic During follow up three patients have died 39 patients and between 151 and 30)2 kPa stone extraction increases with size of the from non-biliary diseases, and only two (2266 mm Hg) in six patients. Dilatation common duct stone. Stones >2 cm are have required endoscopic stent changes for was incomplete in one patient in each traditionally referred for surgery. Patients cholangitis. There were no biliary related group. with recurrent pyogenic cholangitis often deaths. Very high pressures are used in both have large, muddy, calcium bilirubinate These results suggest that when stones forms of stricture dilatation. Balloon dila- stones as the cause of biliary obstruction. can not be removed endoscopically: (1) tation may be inherently safer and more From January 1985 to November 1986, we temporary stenting permits further elective effective as these pressures are applied only had 32 patients (M= 12, F=20); age 36-85, endoscopic or surgical therapy; (2) long- http://gut.bmj.com/ in a radial direction, but this awaits confir- mean=69 years), with CBD stones greater term stent placement may provide a useful mation. than 2 cm (greatest diameter 2-0-3-6, therapy for poor risk surgical candidates. mean=2-8 cm). The mean diameter of the distal CBD was 1-)6 cm; 47% had signifi- cant cardiorespiratory problems. Seventeen Endoscopic sphincterotomy for common bile (53%) had acute suppurative cholangitis Open access colonoscopy: a single investiga- duct calculi in patients with gall bladder in requiring emergency drainage with a naso- tion for suspected colonic neoplasia situ considered unfit for surgery biliary catheter. Stone extraction was on September 26, 2021 by guest. Protected copyright. attempted with large (6 cm) baskets and JJ T TATE AND G T ROYI.F (INTRODUCED BY B R DAVIDSON, J P NEOPTOLEMOS, AND D 1. mechanical lithotripsy after sphinctero- I TAYLOR) (University Surgical Unit, Royal CARR-ILOCKE (Departments of Surgery and tomy. Chemical dissolution was performed South Hampshire Hospital, Southampton) Gastroenterology, University of Leicester, with 1% EDTA solution infused via the It has been suggested that colonoscopy Leicester) Endoscopic sphincterotomy (ES) nasobiliary catheter. should be the primary investigation of was attempted in 106 patients with common Sixteen (50(%) had duct clearance after a occult or overt colonic bleeding. We report bile duct (CBD) calculi and gall bladders mean of 2-8 sessions (range 1-5) with no the results of providing an open-access present who were considered unfit for mortality. The main reason for failed duct colonoscopy service to general practitioners surgery on the grounds of age and frailty clearance was the lack of space within the for such patients. alone (35%) and/or the presence of major CBD to open the basket. Sixteen with failed All general practitioners in one health medical problems (65%). Endoscopic duct clearance underwent surgery (explora- district were advised of the service by letter. sphincterotomy was successful in 105 cases tion of CBD one, choledochoduodenos- Patients were sent an appointment to attend (99%). Early ES related complications tomy 15) with two deaths. for colonoscopy without prior hospital occurred in 21 patients (19-8%). There We conclude that a combined use of large interview, sigmoidoscopy or barium enema. were 12 hospital deaths (11-3%) of which baskets and chemical dissolution with I % In a 12 month period 138 referrals were five were due to biliary causes (4-7%). EDTA and if necessary, mechanical litho- received from 53 general practitioners. Complications were more frequent in tripsy can remove CBD stones of >2 cm Colonoscopy was performed on 131 patients in whom initial ES did not clear the with safety. patients (age 19-83, median 63 years). Six CBD (p<002) and mortality was greater in patients did not attend and colonoscopy was those without confirmation of CBD clear- contraindicated in one. The entire colon ance (p<0()1) unless operated upon. Endoscopic prosthesis for common bile duct was examined in 92% and there were no Twelve patients developed gall bladder stones complications. Findings were carcinoma in Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1 372 The British Society ofGastroenterology 12 patients (Dukes' stage A =4, B=3, Fructose and sorbitol malabsorption in lated hernias 59 (25%), volvulus 10 (4'S), C=5); adenomatous polyps in 22; diverticu- patients with functional bowel disease acquired megacolon 6 (4%/O ), pseudo- lar disease in 35; colitis in 9 and no abnorm- obstruction 4 (2(%), faecal impaction 6 ality in 53. J J RUMESSIN AND) [(UDMAND-HOYER (INTRO- (30/O%), and miscellaneous 18 (6"%). The peak We conclude that open access colono- DUCED BY P M CIIRISIIANSiN) (Dept oJ incidence of obstruction due to adhesions, scopy has provided a rapid, safe and com- Sulrgical Gastroenterology, Hvidovre hernias and intra-abdominal malignancy plete examination of the large bowel with a University Hospital, Denmark and Depart- each occurred in the eighth decade of high detection rate for neoplasia (26%) and ment of Gastroenterologx, and Internal life. Urgent surgery (within 48 hours of has combined treatment (polypectomy) Medicine F, Gentofte Hospital, University of admission) was performed in 300% of with diagnosis in two thirds of these cases. Copenhagen, Hellerup, Denmark) The adhesions (22), 61%o hernias (40), and 30%o absorption capacities and the symptom pro- intra-abdominal malignancies (18). Overall duction of fructose, sorbitol, fructose- mortality was 11 '4%o (26 deaths) and post- Open access fibresigmoidoscopy: a com- sorbitol mixtures and sucrose was investi- operative mortality was 12-3% (19 deaths). parative audit of efficacy gated by means of hydrogen breath tests in Twenty two patients required a total of 2993 25 consecutive patients with functional inpatient hospital days as a result of 1. KAIRA, W R PRICE, B J M JONES, AND A N bowel disease. A 25 g dose of fructose was intestinal obstruction. Strangulated hernias HlAMLiYN (Department of Gastroenterology, malabsorbed by 13 patients, in seven of and large bowel malignancy still account for Russells Halland Wordsley Hospital, Dudley these the absorption capacity was below over 50%, of all cases of intestinal obstruc- Health District, Dudley) We studied 541 15 g. In contrast, malabsorption of sucrose tion in the UK today. A more aggressive open access referrals and compared them to was never seen. Fructose malabsorption approach aimed at earlier detection and 495 hospital initiated fibresigmoidoscopies caused significantly increased abdominal elective treatment of both conditions should over five years. Though the number of open distress compared with the group of patients be balanced against the risk of postoperative access fibresigmoidoscopies doubled over with complete absorption of fructose or morbidity + mortality in what is pre- this period, diagnostic yield remained compared with ingestion of sucrose. A 5 g dominantly an elderly age group. unchanged at 40(% and was similar to the dose of sorbitol was malabsorbed by eight of yield in hospital initiated procedures. the fructose malabsorbers. Mixtures of 25 g Colorectal carcinoma was seen in 64 open fructose and 5 g sorbitol caused significantly access compared to 47 hospital referred increased malabsorption and abdominal Studies on the genesis of colic patients, the proportion of Dukes' A lesion distress, and in eight of the fructose mal- M A STCOKES, K J MORIARTY, AND B N being similar in both groups (34%S0). absorbers the effect on malabsorption was CATCIIPOILt Carcinoma was not seen in patients under more than additive. (Departments of Surgery anid Medicine, Universities of Manichester anid 40 years of age. Fibresigmoidoscopy was These results show that malabsorption of http://gut.bmj.com/ unsatisfactory in 54 (open access 31, small amounts of fructose, sorbitol and We.stertn A lstralia, Hope Hospital, Salford) 'Colic' is a clinical term hospital 23) and pathology was missed in 12 mixtures thereof is significant and which has defied definition. We (open access seven, hospital five) patients. symptom provoking in patients with func- precise have examined the motor events in the gut There were no significant operator differ- tional bowel disease. The findings may have associated with ences. direct implications for the dietary guidance simulated 'colic'. Two 5-lumen tube systems, a were High diagnostic yields were associated to a major group of patients with functional each carrying balloon, with diarrhoea and rectal bleeding (900%), bowel disease and raise the possibility of used. One lumen inflated the balloon while rectum in two sensed pressure proximally and two altered blood per (95%) and rectal defining separate entities this disease on September 26, 2021 by guest. Protected copyright. bleeding associated with pain (100(%). Low complex. distally to it by suitable ports, which thus yields were associated with abdominal pain assessed contractions over 24 or 32 cm of as sole cause of referral (0%), constipation gut. Sensing channels were water perfused (9.3%) or abdominal pain with constipation (0(2 ml/min) and recorded via transducers (8-2%). Diagnostic rate was significantly Current spectrum of intestinal obstruction on a rectilinear polygraph. 'Colic' was low in open access patients under 40 years of induced by balloon inflation followed by age (19-22%). Ci P MCEN'I'EE, D PENDIR, r) MULVIN, M saline bolus injection via the port immedi- Referral was considered justified in 475 MCCUIIOUGH, S NAIEDEDR, S PARAH, M S ately orad to it. Studies were made of the (87:8%) patients and only 54 (16'6%1o) BADURDEEN, V FERRARO, C ClHAM, N GIIAI.11AM, duodenum, jejunum, ileum and colon, AND P MA'ITHEWS or patients with a normal endoscopy required (North Tees General, passing the tube system orally, via stomas further investigations. Darlington Memorial, Bishop A ucklaind per rectum. We conclude that open access fibresig- General, Hartlepool General Hospitals) This (1) Pain was invariably associated with a moidoscopy is effective and cost efficient. prospective study was set up to accurately rise of baseline pressure, indicating contrac- Appropriate patient selection on basis of determine the current spectrum of intestinal tion in a gut segment, at least 6 cm and age and symptoms can reduce referrals by obstruction in the UK. During a 12 month sometimes 32 cm long. (2) With pain, basie- '85-1 38% and improve diagnostic yield by 25% period (1 Aug July '86) 228 patients line pressures varied widely between without affecting sensitivity. required a total of 236 admissions to one patients. (3) Solitary painless contraction of four neighbouring district general waves of >25() mm Hg occurred. (4) Dura- hospitals serving a total population of tion of pain was similar in both small (44+ 13 591 000- an overall incidence of 39-9 cases sec, mean+SD) and large (38±17 sec, per 100 t)00 per annum. Aetiological factors mean ±SD) intestine. (5) Location of pain, included adhesions 75 (32%), intra- referable to gut segments, was variable; FUNCTIONAL BOWEI. abdominal malignancy 61 (26%), strangu- with increasing severity, pain spread across Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A1373 the midline. We suggest a definition of using the HAD scale and the General ing. Six of the 19 cases had a smooth muscle 'colic' as 'a phasic pain usually lasting less Health Questionnaire. Their psychological disorder- for cxample, visceratl myopathy. than one minute with a slow rise to maxi- state was assessed preoperatively and six to inclusion bodies etc. which could only bc mum severity and a similar decline'. 12 months postoperatively and the results diagnosed on electron microscopy. Our compared with a group of age/sex matched data suggest that the vast majority of' allied controls (n=5-). Statistical analyses were functional bowel disorders can be diagnosed Mouth-to-caecum transit time in man is performed using the Mann Whitney U two by examining a full thickncss rectal biopsy reduced by a novel serotonin M-receptor tailed test. Constipated patients had signifi- by immunocytochemistry, silver impregna- antagonist cantly higher HAD depression scores com- tion and electron microscopy. pared with controls (6 (2-12) v 4 (0-8), L MELEAGROS, B KRFYMANN, M A GHATEI, AND p<0)-(5). Patients who were improved S R BLOOM (Department of Medicine, Royal (n= 13) by operation could be identified Postgraduate Medical School, Hammer- preoperatively by significantly lower HAD anxiety scales compared with those who smith Hospital, Du Cane Road, London) GASTROI)UODEINAL The novel selective serotonin M-receptor were not improved (n=8), 8 (3-14) 15 (5-HT3) antagonist ICS 205-930 (Sandoz) (1t)-19), p<0-()2) and by significantly lower HAD depression scores (4 (2-12) v 7 Effect of indomethacin and ranitidine on enhances gastric circular muscle contrac- gastric acidity tions in vitro and gastric emptying in vivo in (5-I1), p<0'01). Operation itself, how- guinea pigs, being 100 and 5() times more ever, had no influence on psychological scoring. Incontinent patients did not differ R P WAIL, P PRICIIARD, r DANESHMINI), N potent than metoclopramide. We therefore SMITH, AND M I ANGMAN (Department oJ investigated its actions in eight fasted from the controls using the parameters tested and the group improved by operation Therapeutics, University Hospital, Notitig- normal volunteers (ages 23-33) in a ham) The non-steroidal anti-inflammatory randomised double blind crossover trial. (n= 14) could not be identified preopera- tively. agents have been implicated in the patho- After an initial rest period ICS 205-930 20 genesis and complications of peptic ulccr. It mg or placebo were administered by slow iv These data indicate that only constipated patients have a personality disorder and is unclear which mechanisms are involved, injection (time 0). At + 15 min the subjects but increased acid secretion could be one. consumed a test breakfast (530 kcal) includ- that those likely to be improved by opera- tion can be identified beforehand. Indomethacin enhances histaminergic and ing a glass of orange juice containing 25 ml basal but not food stimulated acid secretion. lactulose and were studied for a further 18X) Prolonged unbuffered acidity is also an min. Mouth-to-caecum transit time was important factor in peptic ulcer treatment. estimated by breath hydrogen analysis of 5 Diagnosis of allied functional bowel dis- We have therefore investigated the effects minute 20 ml samples of end tidal exhaled orders using monoclonal antibodies and of indomethacin and ranitidinc on noctur- http://gut.bmj.com/ air using an electronic monitor. A sustained electromicroscopy nal gastric acidity in 1i) normal volunteers. rise in breath hydrogen of 3 ppm or more Each underwent four randomised studies was considered significant. Blood samples P PURI, T FUJIMOTO, AND BRIAN LiAKE (C after seven days treatment with indometha- for gut hormone measurements were taken FEIGHERY) (The Children's Research Centre, cin (50 mg tds) and/or ranitidine (300 mg at at intervals throughout. ICS 205-930 pro- Our Lady's Hosp for Sick Children, 1900 h), or placebo (double-dummy). duced a significant decrease in mouth-to- Crumlin, Dublin 12 and The Hosp for Sick Acidity was measured on half hourly caecum transit time (mean ±SEM min): ICS Children, Great Ormond Street, London) aspirates of gastric contents from 1900 h to 205-930 93±8, placebo 121±9 (p<0-05 There are a number of conditions which ()800 h. Environmental conditions including on September 26, 2021 by guest. Protected copyright. paired t test). Drug administration did not clinically resemble Hirschsprung's disease meals were identical on each study day. alter the gut hormone profile. We have thus despite the presence of ganglion cells on Median acidity (range) during the night shown that ICS 205-930 significantly rectal biopsy. These conditions have been (220() h-080() h) was 41-7 mmol/l (67-6- reduces mouth to caecum transit time in classified on the basis of symptoms under 25-1) on pla/pla; 39-8 (63-1-24-0) on ind/ man. various names such as pseudo Hirsch- pla; 0)'36 (21.3-0)-) on pla/ran; 0)77 (43-7- sprung's disease, chronic adynamic ileus t)-0) on ind/ran. Ranitidine significantly and chronic idiopathic intestinal pseudo- decreased acidity irrespective of con- Do patients with disordered defecation have obstruction. There have been no systemic comitant indomethacin treatment (p<0)-01, a primary personality disorder? studies to date to distinguish these condi- Wilcoxson) and indomethacin alone did not tions from one another. We examined significantly affect acidity. This suggests S E FISHER, M R B KEIGHI.EY, K BRECON, V biopsy and surgical specimens from 19 cases that ulcerogenic effects of indomethacin are SMART, AND H ANDREWS (Department of of allied functional bowel disorder by not due to increased acidity and that raniti- Surgery, The General Hospital, Birming- enzyme histochemistry (AChE), silver dine should be effective therapy even in ham) It is uncertain whether patients with impregnation and electron microscopy in an patients receiving indomethacin. disordered defecation have a personality attempt to establish the most appropriate disorder. We investigated patients with diagnostic procedure. A monoclonal anti- chronic constipation (n=21) and faecal body D7, produced in our own laboratory is Isolated duodenal tamponade in the treat- incontinence (n=29) who were offered a good marker of the autonomic nervous ment of bleeding duodenal ulcer surgical treatment. Patients were sub- system. This unique antibody distinguishes divided into those whose symptoms were various neuronal abnormalities of the bowel T V lAYl!OR AND A 1. BLOWER (Department of controlled by surgery and those who were except abnormalities of the argyrophil Surgical Gastroenterology, Manchester not improved. Patients were investigated plexus which are diagnosed by silver stain- Royal Infirmary, Oxford Road, Man- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1374 The British Society ofGastroenterology chester) The overall mortality for bleeding operation in the intervening period, how- pathophysiological basis is not known. To duodenal ulcer remains today, as it has ever- either hemigastrectomy or pyloric investigate this, 30 patients (male. 95% age: throughout this century, at 10%. Endo- reconstruction. The endoscopic proven 35 23+1 79, smokers 33.3%) with active scopic methods of arresting haemorrhage recurrence rate for HSV was 5%. DU. documented endoscopically were have appeal but none, including laser, has Although HSV is a technically more recruited for the study. The MAO, the been shown substantially to reduce mor- demanding procedure we regard it as a parietal cell sensitivity to gastrin (D,"C), tality. A simple, low cost, easily available clearly superior operation to TVP in almost fasting and meal-stimulated gastrin method of isolated duodenal tamponade all respects and longterm follow up supports responses were measured. During endo- has been designed and investigated. A this optimism. scopy, three biopsies were taken from the balloon surrounding a central flexible, but body of the stomach for the estimation of non-collapsible tube fits over the distal 7 cm histamine and 2 from the antrum for the of an end-viewing gastroduodenoscope. Nd-YAG laser therapy in patients with estimation of mucosal gastrin. Seven non- This can be easily introduced into the duo- gastric and duodenal malignancies - an ulcer subjects (age 42 7±7-0, male 43%, denal cap on the initial diagnostic endo- initial experience 28-6%YO smoker) were recruited as controls. scopy and if active bleeding is present it is The results (expressed in mean+SE) showed that MAO was significantly higher inflated by means of a 70 cm tube. The J R ANDFRSON AND C G MORRAN (University device fits neatly in the cap and cannot be Department of Surgery, Royal Infirmary, in the smokers (32-3±3-5 mmol/h) than the dislocated after removal of the endoscope. Glasgow) Thirty patients (24 men and 6 non-smokers (24 8±1 9) (p<0)05). The A standard 1 cm diameter deep ulcer was women) of mean age 67 year (range 48-84) mucosal gastrin content was significantly created in the duodenums of four anti- with gastroduodenal malignancies were higher in the smokers (74.2±16 2 fmol/mg) coagulated dogs. A steady rate of blood loss referred for laser therapy. The reason for than non-smokers (41.7±5.9) (p<0(05) and (12 ml/15 minutes) was achieved over four referral was inoperability (n=14) unfit for both were higher than the controls (15.4+ consecutive 15 minute periods before crea- laparotomy (n=7), widespread metastases 5-7) (p<0)01). In both smokers and non- tion of duodenal tamponade by the balloon. (n=7) and refused surgery (n=2). The smokers the mucosal histamine (28.3+3.4, Haemorrhage was immediately completely tumour sites were fundus in 12 (involving 28-8+5-1 ng/ml), fasting gastrin level arrested and haemostasis remained cardia in 10), body in four, proximal two (5.1+0 5, 5 3+0 8 nmol/l), meal stimulated throughout the rest of the experiment. Two thirds in two, distal two-thirds in five, gastrin response (1.51±0.15 and 1 68±0-29 high risk patients on ventilators were antrum in three, total stomach in three, and nmol/min/l) and Ds(C (144.6±36.1, treated by tamponade which immediately 2nd part duodenum in one. The major 156-3±66-3 ng/kg/h) were similar. We con- arrested haemorrhage from their duodenal symptoms for which relief was sought were cluded that the increased MAO in smokers ulcers, one had a further small bleed follow- bleeding in 21, dysphagia in 11, and vomit- is associated with increase in antral gastrin, ing removal of tamponade. ing from gastric outlet obstruction in eight. suggesting that the latter is important in the http://gut.bmj.com/ On average two laser sessions (range 1-7) pathogenesis. were given to each patient. Is highly selective vagotomy (HSV) a good Relief of symptoms was achieved in 19 of operation for duodenal ulcer (DU)? A longer the 21 patients with bleeding, 10 of the 11 Basal and stimulated plasma gastrin in duo- look at the answer patients with dysphagia with recurrence of denal ulceration (DU): correlation with symptoms needing Celestin intubation in failure of H2 receptor antagonists (H2RA) K S DUA, M KORUT}{,. P W BRUNT, AND N A four, and in five of the eight patients with and with recurrent ulceration (RU) after MATHESON (Departments of Surgery and gastric outlet obstruction. Partial relief of highly selective vagotomy (HSV) on September 26, 2021 by guest. Protected copyright. Gastroenterology, Aberdeen Royal outlet obstruction was obtained in two Infirmary, Aberdeen) Highly selective patients who were able to manage fluids K S NAIK, M LOGOPOUIOS, J N PRIMROSE, R l vagotomy is now well recognised as a treat- only. Seventeen of these patients have, to BLIACKEl71, AND D JOHNSION (University ment for DU although the long term date, died with a mean survival of nine Department of Surgery and Anatomy, The efficacy is less well established. We have weeks. The mean survival of the remaining University, Leeds and Leeds General previously resported the early results (at a 13 patients is 28 weeks (range 3-76 weeks). Infirmary, Leeds) The aim was to determine mean of five years postoperatively) of 137 Palliative laser therapy offers relief of the influence of gastrin and the proposed patients operated on by one surgeon and symptoms to a significant number of 'G-cell hyperfunction' in H,RA resistance randomly allocated to either HSV or truncal patients with gastroduodenal malignancies and recurrence after HSV in 71 DU patients. vagotomy and pyloroplasty (TVP). Highly unsuitable for surgery, in whom therapeutic Basal (BG) and integrated gastrin responses selective vagotomy was significantly options are otherwise limited. to meal (IGRM) and insulin (IGRI) were superior in Visick grading (p=0-05) and measured before and after HSV for DU. side-effects - for example, diarrhoea, BAO, PAO (Pentagastrin) and PAO p=-0.01. Smoking affects mucosal gastrin and gastric (Insulin (I)) were measured pre- and post- We have resurveyed the same patients at acid secretion in duodenal ulcer (DU) operatively. The pre-operative response to a mean of 11 (minimum eight) years post- H.RA was recorded. Patients were followed operatively. There is no difference on blind W M HUI, M CHAN, AND S K LAM (Departments up for five years to detect RU. There was no assessment using rigorous Visick grading of Medicine and Clinical Biochemistry, difference between BG, IGRM and IGRI in between HSV and TVP (Grades 1+11, University of Hong Kong, Queen Mary H.RA resistant and non-resistant or RU and 75-4% and 74 5% respectively). Nearly Hospital, Hong Kong) Smoking adversely non-RU patients. There was a positive one-fifth (18X6%) ofTVP patients (but none affect the healing of DU and smokers have a correlation between preoperative IGRM of the HSV patients) had required re- higher maximal acid output (MAO) but the and postoperative BAO (p= )02). Inte- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 1 375 grated gastrin responses to meal correlated T J CROFTS, R J C STEELE, S C S CHUNG, K PARK, prove more effective in medical manage- inversely with percentage reduction in AND A K C LI (Department of Surgery, The ment, 38 patients with REO were treated BAO postoperatively (p=0'02). An inverse Chinese University of Hong Kong, Hong with omeprazole (OME) 40 mg daily for up correlation was observed between both pre- Kong) With the establishment of H. to eight weeks. Endoscopy, clinical assess- operative and postoperative IGRM and receptor blockers in the treatment for duo- ment and laboratory studies were done at PAO(I) (p=0-03). A positive correlation denal ulcer combined with the use of effec- the start, at four weeks and at eight weeks was shown between postoperative IGRI tive antibiotics, we studied if surgical inter- (if unhealed earlier). Oesophagitis was and postoperative PAO(I) (p=0 03). vention is always indicated for patients with graded 0-4. The demographic features G-cell hyperfunction is not an important perforated duodenal ulcer disease. were: mean age 61 years; males 50%; cause of resistance of H,RA or of RU after Eighty four consecutive patients with smokers 32%; regular NSAID users 11%; HSV. Correlations between preoperative definite diagnosis of perforated duodenal obese 47%; mean duration of symptoms 9-9 IGRM and postoperative BAO and per- ulcer were randomly allocated to one of two years. Cimetidine treatment, before OME centage reduction in BAO have been treatment groups, surgery or non-operative therapy, was on average: at 1-6 g daily, demonstrated. Some of the acid response to (antibiotics, nasogastric suction and H2 18 months; at 2 g, 16 months; at 3-2 g, insulin after HSV appears to be mediated by receptor blockers) treatment. The types of five months (total 39 months). Endoscopic gastrin. surgery performed depended on the patient appearances improved in 28 patients after fitness and the surgeons' experience. All four weeks' treatment and in a further seven conservatively treated patients were by eight weeks. The cumulative changes at Recurrence of duodenal ulcers during managed by one team and constantly eight weeks were: healed 42%; almost com- maintenance treatment assessed. If there was no improvement by 12 pletely healed 45%; unchanged 13%. hours after admission, they were referred Symptoms were completely relieved in J PENSTON, D CARTER, AND K G WORMSLEY for surgery and deemed a failure of con- 58%, improved in 32%, unchanged in 80%. (Ninewells Hospital, Dundee) The clinical servative therapy. Adverse events were infrequent and did not course of 413 patients with endoscopically There was one trial exclusion leaving 83 require discontinuing OME. There were no healed duodenal ulcer has been studied. patients for analysis; 40 in the conservative clinically significant changes in haema- Thirty seven of the 339 patients (11%) group and 43 in the surgery group. Both tology or in biochemistry. Of 28 patients receiving maintenance treatment with an groups were comparable for age, sex, ulcer- returned to maintenance CIM, 50% were in H, receptor antagonist suffered their first ogenic factors and presence of coexistant remission after 1-19 months. In conclusion, relapse during the first year; 44/268 (16%) disease. omeprazole heals or improves oesophagitis during the second year; 21/168 (13%) Ten patients (25%) failed on conserva- and relieves symptoms when refractory to during the third year; 11/105 (10%) during tive therapy but 75% of patients did not high dose cimetidine. the fourth year and 3/51 (6%) during the need surgery. fifth year. Sixty three per cent of first Overall mortality was 4-8% and equal in http://gut.bmj.com/ relapses were asymptomatic. After endo- both groups. Comparison of morbidity scopically confirmed rehealing of the first between conservative therapy versus Omeprazole or ranitidine in the treatment of - relapse, 50 patients again received main- surgery as measured by abscess formation reflux oesophagitis result from a double tenance treatment with 150 mg ranitidine at (6 v 2), hospital stay (12 days v 8-8 days) and blind, randomised, Scandinavian multi- night while 46 patients received mainten- duration of antibiotic treatment (7.8 days v centre study ance treatment with the increased dose of 5-7 days) all favoured the surgery group. L LUNDELL, 0 FAUSA, AND S SANDMARK 300 mg at night. During the first year after However a subgroup was identified in which rehealing, 3/46 (7%) patients receiving 150 conservative management may be indicated (INTRODUCED BY A WALAN) (Dept ofSurgery II, Sahlgrenska Sjukhuset, Goteborg, Dept on September 26, 2021 by guest. Protected copyright. mg ranitidine at night relapsed, compared in preference to surgery. with 0/43 receiving 300 mg ranitidine. The of Medicine A, Rigshospitalet, Oslo, and subsequent relapse rates were 1/26 (4%) Dept of Otorhinolaryngology, Regionsjuk- and 1/34 (3%) during the second year of huset, Orebro, Norway) One hundred and further maintenance treatment and 2/17 fifty two patients with erosive and/or ulcera- (12%) or 1/17 (6%) during the third year, tive oesophagitis were randomised to treat- respectively. OESOPHAGUS ment with omeprazole 20 mg, once daily or We conclude that maintenance treatment ranitidine 150 mg bid. Endoscopy was done is effective in sustaining remission of the Value of omeprazole in the management of immediately before entry and after four and majority of patients with duodenal ulcer. erosive oesophagitis refractory to high dose eight weeks' treatment together with assess- The relapse rate during maintenance treat- cimetidine ment of symptoms. Macroscopic healing of ment decreased significantly during the oesophagitis was defined as complete course of time. Patients who developed K D BARDHAN, PAMELA MORRIS, MARY epithelialisation of all oesophageal lesions. recurrence during maintenance treatment THOMPSON, D S DHANDE, R F C HINCHLIFFE, M One hundred and forty four patients com- seemed more likely to remain in remission if J DALY, N J H CARROLL, AND CATHERINE pleted the first four weeks of treatment a higher dose of gastric secretory inhibitor KRAKOWCZYK (District General Hospital, according to the protocol and the healing was used for treatment. Rotherham and Astra Clinical Research rates were 67% for omeprazole and 31 % for Unit, Edinburgh) Refractory erosive oeso- ranitidine (p=0'00(1). The same great phagitis (REO) is defined as persistence of differences in healing rates were seen also Prospective randomised controlled trial of ulceration or erosion despite treatment with after eight weeks treatment; 85°% and 50% conservative therapy versus surgery for per- cimetidine (CIM) 3-2 g daily for :'3 months. for omeprazole and ranitidine, respectively forated duodenal ulcer To assess if greater acid suppression might (p A 1376 The British Society ofGastroenterology Omeprazole gave also a faster and more H 1. SMART AND MICHIAEL ATKINSON (Depart- (800 ml) attached. Gastric corpus fundus substantial improvement in reflux symp- ment of Surgery, University Hospital, pressure was recorded during distension of toms. In the overall evaluation of symp- Nottingham) Antacid and alginate or the bag with 460±(30 ml (mean+SD) of air toms, treatment with omeprazole was dimethicone combinations are perhaps over 30 seconds. Pressure indices (median: superior to ranitidine already after one superior to simple antacids in treating range) derived from areas under the week and throughout the study. Heartburn oesophagitis. As there is a lack of data on pressure curves were: HV; 12-7 (7.5-17. 1) resolved completely in 77% of patients these combinations we have performed a cm H,O and GOR; 9-1 (6-4-13.3) cm H,O receiving omeprazole during the first four study comparing two commonly prescribed (p<0(02 Mann Whitney U test). No correla- weeks compared to 36% in those receiving preparations. Fifty three patients with tion was found between pressure indices ranitidine (p<0.-)001). There were no symptomatic, endoscopically proven oeso- and age, sex or body weight. adverse events or clinically significant phagitis were randomly allocated to receive The result was unexpected. It is, how- changes in the laboratory screen attribut- Asilone gel (28) or Gaviscon liquid (25), 10 ever, consistent with reports of delayed able to the trial medications. The present ml qds for eight weeks. Symptom assess- gastric emptying in patients with GOR. study has shown that omeprazole 20 mg ment and endoscopy were performed at the once daily, is superior to ranitidine both in start and end of the study. Both groups were promoting healing and relieving symptoms comparable for age and sex distribution, Patterns of acid reflux in complicated oeso- in patients with erosive and/or ulcerative alcohol and tobacco consumption, baseline phagitis oesophagitis. symptoms, endoscopy and biopsy scores and withdrawals (three per group). After D A F ROBERTSON, M ALDERSLFY, H SHEPHtERD, eight weeks treatment both agents signific- AND C L SMI1H (Department of Medicine II, antly (p<0.01) improved symptoms, Southampton General Hospital, Southamp- Cisapride and gastroesophageal reflux in Asilone gel (79%/) being significantly ton) Oesophageal manometry and 24 h children with or without neurological dis- (p<0t)-5) superior to Gaviscon liquid (52%) ambulatory pH recordings from the distal orders in relieving heartburn. Only Asilone gel oesophagus were performed in 25 patients (38%) produced a significant (p<002) with complications of oesophagitis G S Cl-ARKE, B SANDHU, N GILBERTSON, AND improvement in endoscopic oesophagitis (stricture, Barrett's oesophagus or oeso- M J BRUETON (Dept of Child Health, West- from baseline scores. Asilone was also phageal ulcer) and compared with 25 minster Children's Hospital, London) superior to Gaviscon (29% v 8% ) in patients with uncomplicated oesophagitis. Cisapride was used to treat 22 children who improving histological scores but this differ- Acid reflux was more severe in the compli- had significant gastroesophageal reflux ence was not statistically significant cated group with 26-20% of time below pH 4 demonstrated by 24 hour pH monitoring. (0-05 The British Society ofGastroenterology A 1377 of Gastroenterology and Medicine, Royal >pH 4) and acid shift (per cent time A1378 The British Society ofGastroenterology motility. Frequency, duration and ampli- University Hospital, Nottingham) Dys- useful means of estimating normal ranges tude of primary peristalsis (PP), secondary phagia for solids is a common problem which demonstrate high sensitivity and peristalsis (SP), and tertiary contractions following antireflux operations and we have specificity. (TC) at 14 cm were quantified for one previously reported a high incidence after minute after balloon inflation under base- insertion of the Angelchik antireflux pros- line conditions, and again after intravenous thesis (ACP). To study this problem we Transthoracic colon interposition for benign injection of 10 mg C. Traces were analysed have performed a marshmallow/barium oesophageal stricture blind with regard to treatment. While C had swallow (MMBS) in the early postoperative no significant effects upon PP or TC, SP was period and at subsequent follow up. The P E BURKE, E MCGOVERN, AND K M SHAW significantly stimulated, SP/min increased oesophageal transit time of the marsh- (INTRODUCED BY G MCENTEF) (Royal City of from 0 (0-1) to 1 (0-4)*, with a duration/ mallow was recorded (normal <1 min). Of Dublin Hospital, Baggot Street, Dublin) min of 0 (0-1-8) increasing to 3-3 (0-10-7) 40 patients we have initial post operative Thirty four consecutive cases of trans- sec* and a maximal amplitude increasing MMBS in 36 patients and of these 24 (66%) thoracic oesophageal resection with colon from 0 (0-20) to 37-5 (0-180) cm HO* were prolonged. We have then repeated the interposition were reviewed. There were 20 after injection of C. The drug may therefore MMBS in 21 patients at a median of 33 men and 14 women ranging in age from two reduce nocturnal acid reflux time by stimu- months (9-48) and this long term MMBS to 83 years (mean 51.4). Causes of strictures lation of SP. (All data as median and range, was prolonged in 15/21 patients (71%). In included: reflux oesophagitis (30), corrosive *p<0.01, Wilcoxon signed rank test.) addition three patients had the ACP ingestion (two), achalasia (one), and removed for severe dysphagia before repeat tracheo-oesophageal fistula (one). The examination was performed. Of eight mean duration of symptoms was five years, Manometric findings in patients with the patients with a normal MMBS postopera- and 18 patients had previous unsuccessful globus sensation tively seven of these remained normal at surgery. A left thoracotomy with the left long term follow up and of 13 patients with colon mobilised through the diaphragm was J C LINSELL, A ANGGIANSAH, AND W J OWEN prolonged transit postoperatively, all always performed. There was one post- (Department of Surgery, Guy's Hospital, remained abnormal. We conclude that operative death (2.9%). Six postoperative United Medical and Dental Schools, St oesophageal transit of solids is significantly complications developed (17.6%), only Thomas St, London) Studies using water slowed by the ACP in many patients and three of which were attributable to the perfused oesophageal manometry systems that this is not a transient postoperative thoracotomy. No anastomotic breakdown have suggested that the globus sensation phenomenon. occurred. Three recurrent strictures may be a manifestation of an oesophageal developed (9%): two oesophagocolic in motility disorder either of the oesophageal children, which were revised surgically, and sphincters or of the body of the oesophagus. one gastrocolic in an adult which required a Using a Gaeltec system of six intra- Expression of normal ranges in 24 hour http://gut.bmj.com/ intra-oesophageal pH monitoring single dilatation. Four patients were lost to oesophageal microtransducers we have per- follow up, and five were asymptomatic until formed manometry on 18 patients (median death. Over 70% of patients have been age 53 years) whose major symptom was LR JENKINSON, T L NORRIS, AND A WATSON (Royal Lancaster Infirmary, Ashton Road, symptom free during a mean follow up 'globus' and who had normal oesophago- period of eight years and all are satisfied scopy and indirect laryngoscopy. Using a Lancaster) The advent of 24 hour intra- oesophageal pH monitoring has revolution- with the result of their operation. station pull through technique the mean Thoracotomy for oesophageal resection lower oesophageal sphincter pressure ised the diagnosis of gastro-oesophageal reflux but there is still no uniform method and left colon interposition is associated (LOS) was significantly lower in the globus on September 26, 2021 by guest. Protected copyright. for the expression of normal ranges. Data with few postoperative intrathoracic patients than in 12 normal controls (p<0-02 and does not predispose to using Wilcoxon's rank-sum test). Four from healthy subjects are usually skewed complications towards zero and the use of the conven- proximal stricture formation in adults. The patients had abnormal motility of the oeso- high level of patient satisfaction confirms phageal body; two having diffuse oesopha- tional ±2 SD from the mean produces negative lower limits. We have investigated that the left colon is an excellent visceral geal spasm and two non-specific motility oesophageal substitute. disorders. There was no significant differ- the use of percentiles as an alternative ence between upper oesophageal sphincter means of expression. pressures in either globus patients or con- Twenty six healthy volunteers underwent trols. Three patients had abnormalities of manometry and 24 hour ambulatory pH Laparoscopy, ultrasound or CT in the detec- upper oesophageal sphincter function. Our monitoring. The upper limits of normality tion of intra-abdominal metastases for oeso- findings suggest that patients with the were estimated from the 90th percentile. phageal cancer? globus sensation do have oesophageal Subjects with two or more abnormal values abnormalities. The finding of hypotensive in either the upright or supine periods were I WAll, DOROTHY ANDERSON, I STEWART, LOS pressures suggests a possible associa- classified as 'refluxers'. Fifty patients with G BELL, AND J R ANDERSON (Departments tion with gastro-oesophageal reflux. endoscopic oesophagitis were then evalu- of Surgery and Radiology, Glasgow Royal ated using this technique. Two (7-7%) con- Infirmary and Inverclyde Hospital, trols were classified as refluxers (specificity Greenock) A number of non-operative Dysphagia for solids is a longterm effect of =92%) and four patients as normal (sensi- options are now available for the palliation the Angelchik antireflux prosthesis tivity=92%). The positive and negative of obstructing carcinomas of the oesopha- predictive values were 93% and 86% gus or cardia. The accurate identification of C S ROBERTSON, D L MORRIS, S AMAR, AND J D respectively. intra-abdominal dissemination is therefore HARDCASTLE (Department of Surgery, We conclude that percentiles provide a important in planning management. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A1379 This prospective study evaluates the cases but was seen in only 12 benign cases Slotervaart Hospital, Amsterdam, Sophia accuracy of ultrasound, CT and laparoscopy (p A1380 The British Society ofGastroenterology progress up the oesophagus in 11 patients for high or low oesophageal lesions, though Twenty patients with endoscopically proven but such progression did not increase the repeated treatment may be necessary. oesophageal variceal bleeding originating risk of malignancy (x2=0O94; p=ns). During from within 2 cm of the OG Junction, were the study eight patients developed severe randomised to receive either 20 mg meto- dysplasia in the columnar epithelium, two SMS 201-995 in the management of variceal clopramide iv or placebo in a double blind progressed to carcinoma in situ and in three bleeding manner. Fifteen minutes after administra- patients an invasive adenocarcinoma tion each patient was re-endoscoped to developed. Diagnosis depended largely R K MCKEE, S D PRINGLE, 0 J GARDEN, A R document whether bleeding had stopped. upon biopsy evidence, as in only one of the lORIMER, AND D C CARTER (University All patients then received sclerotherapy. Of three patients was there macroscopic evid- Departments of Surgery and Medical the 10 patients who received metoclopra- ence of malignancy. These figures indicate Cardiology, Royal Infirmary, Glasgow) mide, nine had stopped bleeding compared that carcinoma occurred once in every 56 Pharmacological arrest of bleeding from to four of the 10 who received placebo patient years follow up, and the relative risk oesophageal varices remains a desirable but (p Atkinson tube (Squam/Adeno/Extrinsic oesophageal varices in 417 episodes of on September 26, 2021 by guest. Protected copyright. 4/6/3) and 14 the tumour probe (5/7/2). which the time of onset was available in 397: Stricturing was upper (AT-1, TP-2), middle Can metoclopramide arrest active bleeding 114 (29%0) with only melaena and 232 (AT-8, TP-2) or lower (AT-4, TP-10). from varices? A prospective controlled trial (58%) with only haematemesis before Three patients were transferred from their admission. The 24 hourly distribution initial treatment groups: one AT to TP S W HOSKING, W DOSS, H EL-ZEINY, M S showed a biphasic pattern with 46% of the (tube displacement), two TP to AT (one BARSOUM, AND AG JOHNSON (Kasr El Aini bleeds occurring between 7 and 10 am refused repeat endoscopies, one probably Hospital, Cairo and Royal Hallamshire (n= 107) and between 20 and 22 pm (n=76). undertreated). Hospital, Sheffield) Active bleeding is still The Poisson heterogeneity test (Armitage Probe treated patients ate a more varied present in 30(% of patients reaching hospital 1972: p 214) was used to assess non random diet, though timed solid swallows showed after variceal haemorrhage. Balloon distribution assuming that the onset of no difference between the groups (95% tamponade, vasoactive therapy or immedi- bleeding would be equally distributed conf limit AT v TP -36 to 9-0 v -04 to 2-2 ate sclerotherapy are not always available throughout 24 hours. The asymmetric dis- mm/sec). Six patients required repeated or effective and an alternative simple tribution was significant for the whole group probe therapy. Complications seen: measure is needed. Previous studies have (p<0-001) and for the subgroups: haema- Atkinson tube group- two perforation (one shown that pharmacological constriction of temesis only (p<0-01) and melaena only pre-insertion dilatation), two tubes dis- the lower oesophageal sphincter (LOS) (p<0001). The time of onset was the same placed, two obstructed by food; Probe causes a marked reduction in flow and for patients who started bleeding in hospital group - one perforation (pretreatment pressure in submucosal varices proximal to or at home. dilatation), one persistant dysphagia. LOS. As 90(% of variceal bleeds occur We do not have an explanation for this The tumour probe and Atkinson tube within the zone encircled by the LOS, we observation but clearly the biphasic diurnal give comparable palliation and appear com- investigated whether such constriction pattern of onset of bleeding from oeso- plimentary. The probe offers an alternative would arrest active variceal bleeding. phageal varices in cirrhotics may have Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroetterology A 1381 relevance to the pathogenetic mechanisms was placed around the bile duct in the Basal pancreatic protein secretion was not related to variceal bleeding. region of the liver hilum. One group of rats significantly affected by CR 1409 (251+64 received 2 ,tg SMS 201-995 sc and a further mg/30 min during saline and 163+44 mg/30 dose six hours later. A control group were min during CR 1409). CR 14(19 strongly dosed similarly with saline. Reticuloendo- inhibited postprandial pancreatic protein PANCREA'I'ICO BILIARY POSTERS thelial system activity was assessed by the secretion from 789+ 119 to 44(1+73 mg/30 hepatic and splenic uptake ofVTechnetium- min (p<0.05), bombesin-stimulated pan- Quantitative 99m-Tc DISIDA scanning in sulphur colloid ('Tc-Sc) and circulating creatic protein secretion from 1328+21( to sphincter of Oddi dysfunction (SOD) levels of endotoxin. Pulmonary function 255±37 mg/30 min (p<0(05), and cacrulein- was assessed by lung compliance, blood stimulated pancreatic protcin sccretion G M FULLIARTON, W R MURRAY, AND T IIILDITCII gases and lung weight. The establishment of from 1274±236 to 442± 147 mg/30 min (Departmenits of Surgery atnd Nuclear pancreatitis was associated an impairment (p<0.0 ). The CCK-receptor antagonist Medicine, Western Inifirmary, Glasgow) of RES activity and pulmonary function. In did not significantly influence pancreatic Sphincter of Oddi dysfunction (SOD) is a rats treated with SMS 201-995, RES volume or bicarbonate secretion. recognised cause of postcholecystectomy function (liver: blood "Tc-Sc 11-9+1-4, These studies show that CCK plays an pain but is a difficult condition to diagnosc spleen: blood 4-2+0-7) was significantly important role in the regulation of mcal and requiring endoscopic biliary manometry higher (p<()0(5) than in controls (liver: bombesin stimulated paincreatic enzyme (EBM) to confirm sphincter motor abnor- blood 0(4+0-07, spleen: blood 0.2+0.05) secretion, but is of little significance for the malities. We have assessed quantitative and the circulating endotoxin levels signific- regulation of basal enzyme secretion and for cholescintigraphy in patients with clinical antly lower (SMS 201-995 12 3±1-6, con- both basal and postprandial pancreatic and manometric evidence of SOD to deter- trols 57-8+4-8 ng/l). Pulmonary function bicarbonate secretion. mine its value as a non-invasive screening was also significantly improved (p<0(05) in tcst. SMS treated rats (compliance 0-58±0X06; Eight postcholecystectomy (PC) patients lung weight 0/o body weight 0.37±0.02) with clinical and manometric evidence of compared with controls (compliance Effect of bombesin on serum trypsin after SOD underwent quantitative 99mTc 0(83+±0)6, lung weight %, body weight various forms of gastric surgery DISIDA scans (group 1). Eight PC patients ).48±0X03). These results suggest that some with non-biliary type abdominal pain of the beneficial effects of SMS 201-995 in J KREUNIN(G, J B M J JANSFIN, AND C B Hi W (group 2) and eight asymptomatic PC ameliorating acute pancreatitis may be l AMERS (Dept Gastroeniterology- patients acting as controls (group 3) also related to stimulation of RES activity. Hepatology, University Hospital Leideni, underwent DISIDA scanning. Scinti- The Netherlands) Infusion of hombesin graphic analysis demonstrated that the T- stimulates several gastrointestinal functions to max (time in minutes maximum counts) including pancreatic enzyme secretion. As http://gut.bmj.com/ was significantly increased in group com- Studies using the CCK-receptor antagonists postprandial pancreatic enzyme secretion is pared with both group 2 (25-9±2-1 v CR 1409 point to an important role for reduced not only in patients with pancreatic 150+±1.5, mean+SEM, p<0-(1) and group cholecystokinin in the stimulation of insufficiency but also in some patients with 3 (25-9+2-1 v 130+±0-6, p<0-01). It was pancreatic enzyme secretion by bombesin previous gastric surgery, we have studied also noted that the T-max values for group 1 and a meal the effect of infusion of bombesin (6(0 pmol/ did not overlap with either those of group 2 kg/20 min) on serum trypsin levels in 1(1 or 3, SOD patients always having values A J 1 DE JONG, N V SINGFR, J B M J JANSE-N, ANI) patients with truncal vagotomy, nine with greater than the highest group 2 or 3 C B H W LIAMERS (Depts Gastroenterology- parietal cell vagotomy, eight with Billroth on September 26, 2021 by guest. Protected copyright. patient. Hepatology, Universities of Nijmegen, 1-gastrectomy, 14 with Billroth 11- We conclude that quantitative chole- Essen and Leiden, FRG anid The Nether- gastrectomy and 11 with gastrectomy and scintigraphy may be a valuable, non- latnds) Pancreatic enzyme secretion is Roux-en-Y anastomosis, and we have com- invasive screening test in clinically assumed to be mediated by both hormonal pared the results with those of nine patients suspected SOD. and nervous mechanisms. The development with pancreatic insufficiency and 11 normal of an in vivo active specific CCK-receptor control subjects. Blood was obtained before antagonist (CR 1409) enabled us to deter- and at the end of the infusion and serum Effects of SMS 201-995 on reticuloendo- mine the role of cholecystokinin (CCK) in trypsin concentrations were measured by thelial system (RES) activity in rats with the regulation of bombesin and meal stimu- radioimmunoassay. Results, expressed as acute pancreatitis lated pancreatic enzyme secretion. Six con- median and range, were analysed by scious dogs, equipped with a gastric fistula Wilcoxon's rank sum test. S A JENKINS, S EILILENBOGEN, [) W DAY, and a cannulated pancreatic duct, were Incremental serum trypsin in the patients N ROBERIS, ANI) J N BAXTIIR (Departments studied for one hour basally and two hours with parietal cell vagotomy (453; 65-20385 of Surgery, Pathology and Chemical Path- after intragastric instillation of a standard [tg/l), Billroth 1-gastrectomy (486; 115-87(1 ology, Royal Liverpool Hospital, Liver- test meal or infusion of 90 pmol/kg/h fig/I), Billroth II-gastrectomy (619; pool) The aim of this study was to establish bombesin or 30 pmol/kg/h cacrulein. In 51-1002 fig/lI), and gastrectomy with Roux- whether or not some of the beneficial effects these studies either 2 mg/kg/h CR 1409 or en-Y anastomosis (317; 19-95(1 fg/I) were of SMS 201-995 in ameliorating acute saline were infused in random order. not significantly different from the results in pancreatitis are attributable to changes in Peak plasma CCK concentrations were the normal subjects (697; 199-9975 fig/I). RES activity. Pancreatitis was induced with similar after the meal and during the infu- However, in the patients with truncal a common bile duct ligature in male Wistar sions of bombesin and cacerulein, 7.2±0.8. vagotomy incremental serum trypsin (140; rats. Twelve hours later a second ligature 8X6±0 8 and 8X1±1 2 pM, respectively. 8-43(1 fg/I) was significantly lower Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 138X2 The British Society ofGastroenterology (p<0(005) than in the normal subjects, but severely limited by the heterogeneous contraction and scarring of that area of the still higher (p hours. Additionally, groups a, b, c received p The British Society of Gastroenterology A1383 its tip. Intraluminal bowel gas and bone are their disease and pancreatic duct reflux. operative ES for CBD stones (group A) and by-passed by this technique. By applying a Men have a larger duct system and different to post-ES complications in 190 patients high frequency transducer within a few anatomical disposition of the sphincter of (group B). Complications occurred in 83 millimetres of the pancreas, high resolution Oddi which predispose to pancreatitis. patients (26%) in group A and in 32 (17O) images of the entire pancreas and ad'jacent in group B. organs are obtained in over 90% of patients. By univariate analysis age and serum The resolution achieved is better than any Computer history analysis in acalculous urea, creatinine, albumin (ALB) and other cross-sectional imaging technique. biliary pain bilirubin (BIL) were all associated with Endoscopic ultrasound is employed in the significant complications in both groups t0-20% of cases of pancreatic disorders in G T SUNDERILAND, R P KNILL-JONES, G P CREAN, (p=(003 to <0-001). In group A, however, which important imaging questions remain AND D C CARTER (University Department of only BIL, medical risk factors (MRF) and after standard investigations. We have done Surgery, Glasgow Royal Infirmary and previous use of ES, were independently over 100 such examinations, and this poster Diagnostic Methodology Research Unit, significant; the probability of complications illustrates by case studies the value of the Southern General Hospital, Glasgow) The was logit p-0-51 (MRF)+0.53 (ES)+0(003 technique for each of the six main reasons of decision to investigate acalculous biliary (BIL) -1-63 - for example, the probability referral: (1) evaluation of a pancreatic mass pain (ABP) rests on the history alone, of complications with BIL=25 ftmol/l, of uncertain nature, (2) final staging of small however, the commonly used 'biliary MRF and ES both=- was p=(- 17 and with pancreatic neoplasm prior to surgery, (3) history' has not been defined. We took a BIL=400()mol/l, MRF and ES both= I, localisation of islet cell tumours, (4) evalua- detailed history using a computer aided this was p=0 637. In group B, only BIL and tion of focal pancreatic duct abnormalities diagnostic system and compared the ALB were independently significant; logit discovered on pancreatography, (5) evalua- features present in patients seen and refer- p- 1-46- 0-107 (ALB)+0-0()4 (BIL) (for tion of early chronic pancreatitis, particu- red for investigation of ABP by general example with BIL=25 [tmol/l and ALB=40 larly the parenchymal rather than ductal surgeons (n=64) with those of confirmed g/l, p= 006 and with BIL=400( tmol/l and abnormalities, (6) evaluation of low biliary gallstone disease (n=57) and those present ALB=20 g/l, p=0 68). obstruction of uncertain nature. in 'dyspepsia' (n= 1119). We conclude that (1) all jaundiced In our institution EUS is now the most Acalculous biliary pain patients were patients with CBD stones are at risk, (2) specific imaging test in the diagnosis of diagnosed on a 'biliary history' and negative patients with medical risk factors should be pancreatic disease. investigations. The decision to operate was treated by ES, alone and (3) 'fit' patients are based on continued symptoms and 25 have best treated by surgery. come to cholecystectomy with 85% Sex differences in gall stone pancreatitis improved (mean follow up nine months). Of the 39 non-operated patients 381% Ingestion of coffee stimulates plasma chole- http://gut.bmj.com/ T V TAYLOR, S RIMMER, C P ARMSTRONG, S B improved spontaneously, 51% are cystokinin secretion and gall bladder con- l.UCAS, AND J JIEACOCK (Department of unchanged and I11% are worse. traction in man Surgical Gastroenterology, Manchester Data analysis showed close similarities Royal Infirmary, Oxford Road, Man- between ABP and gallstone patients except B R DOUGt.AS, C W KOCti, J B M J JANSEN, ANI) chester) From a computerised data base that gallstone patients had significantly C B H W l.AMERS (Depts Gastroenterology- comprising 36 pertinent items in each of 664 shorter histories and suffered more fre- Hepatology and Radiology, University patients with cholelithiasis, differences quent 'attacks' of pain. Acalculous biliary Hospital Leiden, The Netherlands) It has were studied between men and women. In pain patients were quite different to been noted that there is an association 52 patients there was a documented attack 'dyspepsia' patients. There were no differ- between coffee drinking and carcinoma of on September 26, 2021 by guest. Protected copyright. of acute pancreatitis (7-08%). Twenty five of ences between patients who had chole- the pancreas. Furthermore, ingestion of 175 men had pancreatitis compared with 27 cystectomy and those who did not. With the coffee has been held responsible for the of 489 women (p<0'0001). Although men exceptions noted, the symptoms considered induction of colics in gall stone patients. As with uncomplicated gall stones underwent important in our population for the diagno- cholecystokinin (CCK) has major stimu- surgery at a greater age than women they sis of biliary disease are present in the latory actions on both pancreas and gall developed pancreatitis earlier (p<0-00 1). A history of patients thought to have ABP. bladder, we have studied the effect of coffee history of flatulent dyspepsia, chronic on plasma CCK in five healthy volunteers cholecystitis and biliary colic was less (5 M, age 27-38 yr). After an overnight fast common in men than women with pan- Multivariate analysis of risk factors in one of three 165 ml isothermic (70°C) and creatitis (p<0-00l). Men with pancreatitis patients undergoing surgery and/or endo- isosmotic (113 mOsm/l) solutions (sodium had fewer stones in their gall bladders than scopic sphincterotomy (ES) for common bile chloride, caffeinated and decaffeinated women (X2=9'=8 p=0-002). The common duct (CBD) stones coffee) were ingested in random order. Gall bile duct and cystic duct in the pancreatitic bladder volumes were measured by real patient were more likely to be dilated J P NEOPTOlEMOS, D E SHAW, B R DAVIDSON, time ultrasonography and plasma CCK was (p<0-0001); in the non-pancreatitic group AND D L CARR-LOCKE (Departments of determined by a sensitive and specific radio- these ducts were larger in men. Pancreatic Surgery and Gastroenterology, Leicester immunoassay at -5, 0, 10, 20, 30, 40, 50, duct reflux on operative cholangiography Royal Infirmary, Leicester) Multivariate and 60 minutes. was more common both in patients with analysis of clinical, laboratory and medical Ingestion of caffeinatcd coffee induced pancreatitis 64% cf 16% (p<0 0001) and in risk factors was undertaken in relation to an increment in plasma CCK of 2.9± 11 men (p<0-0001). Men are more susceptible postoperative outcome in 325 patients pM (p A1384 The British Society of Gastroenterology feinated coffee resulted in lower, though DAN Z BRAVERMAN (INTRODUCI-D BY M 0-96±0-27) before and 0-73-1-90 cm significant (p<0(05), increases in plasma SININER) (Gastrointestinal Unit, Shaare (mean +SD= 1-16±0-29) after cholecystec- CCK (1-9±0.8 pM) and reductions of gall Zedek Medical C(entre, POB 3235, tomy (p<0-00000l Student's paired t test). bladder volume (5.8± 13 cmI). Ingestion of Jerusalem, Israel) Gall bladder contraction The magnitude of dilatation shows a posi- the sodium chloride solution failed to sig- (GBC) was measured hy real time ultra- tive correlation with time after surgery nificantly stimulate plasma CCK release sonography in 20) subjects: eight healthy (Pearson's correlation coefficient=t)0416, (0(2±0+1 pM) or to induce gall bladder controls and 12 with irritable bowel syn- p<0)'02). contraction (3.0±4.0 cm3). drome (IBS). The technique was used as We conclude that (1) the bile duct on Both caffeinated and decaffeinated previously described (N Engl J Med 1980; ERC dilates after cholecystectomy, (2) the coffee stimulate secretion of CCK and gall 302: 362). The irritable bowel patients were progressive increase in duct size with time bladder contraction. This effect is not medi- randomly recruited to the study when it was suggests that postoperative dilatation is a ated by distension or osmotic or thermic evident that they had a complete negative physiological phenomenon rather than over factors. The finding that caffeinated coffee work-up and their complaints were compat- distension during ERC. was more potent than decaffeinated coffee ible with the criteria introduced by Manning indicates that not only caffeine but also (Br Med J 1978; 2: 653). Fasting volumes other factors are involved in the coffee were twice as large in the IBS (30(37±3.0 Urgent endoscopic drainage in acute induced CCK release and gall bladder con- ml) as in the control subjects (15.15±0+69 suppurative cholangitis traction. ml, p<0-001). Residual volumes were also twice as great in those with IBS compared J W C LEUNG, S C S CiIUNG, AND A K C LI with the control subjects (12.91±2-18 ml v (Combined Endoscopy Unit, Prince of 5-6+0-58 ml, p<0-(l). Increased fasting Wales Hospital, The Chinese Univer.sity ofj Sphincter of Oddi motility in acalculous and residual gall bladder volumes in the IBS biliary pain Honig Kontg, Hong Kong) Acute suppura- are changes that may promote sequestra- tive cholangitis is caused by bacterial infec- tion of cholesterol or calcium salts in the gall tion of the biliary tract superimposed upon (i I SUNDERIAND, C G MORRAN, AND D C bladder of patients with lithogenic bile. biliary obstruction, often complicated by CAR I ER (University Department of Surgery, Impaired GBC has been previously shown septicaemia and shock. The classical treat- Royal Infirmary, Glasgow) Gall bladder in pregnant women and in people with ment is urgent surgical decompression of contraction is considered to be the source of diabetes, coeliac disease, post-vagotomy the biliary tract. Between January 1985 and symptoms in patients with acalculous biliary and cystic duct syndrome. In this study March 1987, 100 patients (44 men, 56 pain. Motor abnormalities of the sphincter GBC is shown for the first time to be women; aged 24-95, mean=69 years) with of Oddi are recognised after cholecystec- impaired in the IBS. acute cholangitis underwent endoscopic tomy but it is not known whether these retrograde cholangiography (ERC) during http://gut.bmj.com/ disorders result from surgery or pre-exist. the acute illness (mean interval 1-7 days, Using ERCP manometry we have Bile duct diameter after cholecystectomy: assessment by pre and postoperative ERC range six hours to eight days after admis- examined sphincter motility before chole- sion) with a view to urgent endoscopic cystectomy in 18 patients thought to have drainage. The causes of cholangitis were: acalculous biliary pain. The papilla of Vater S C CiUNNG,S J W C I[UNG, S D MOK, AND)A K C I (Combined Endoscopy Unit, Prince of common duct stones 85, intrahepatic stones was cannulated with a triple lumen catheter three, malignant obstruc- and a hydraulic capillary infusion system Wales Hospital, The Chinese University of eight, parasites Hong Kong, Hong Kong) Whether the tion one, uncertain three. Ninety eight per used to perfuse each channel with degassed cent of patients had pain, 85% were febrile, water. Measurements were made of the common bile duct increase in size after on September 26, 2021 by guest. Protected copyright. frequency of phasic contractions and of cholecystectomy is controversial. We com- 800o were jaundiced. Eighty seven per cent pared the greatest diameter of the bile duct had leucocytosis and 96% had deranged basal and peak pressures referenced to LFTs and 40)% were in septicemic shock. duodenal pressure. Eight patients were on endoscopic retrograde cholangiography (ERC) before and 4-12 months after chole- The common duct was successfully cannu- given bolus intravenous injection of chole- 98 The tract was cystokinin (I unit/kg) and recordings cystectomy. One hundred and fifty two lated in patients. biliary patients with uncomplicated gall stone drained by sphincterotomy alone (six), repeated three minutes later. Twelve of the catheter or 18 patients showed abnormal sphincter disease underwent pre-operative ERC. insertion of a nasobiliary (26), motility. Basal pressure -30 mm Hg was Forty three asymptomatic patients agreed both (65). Endoscopic drainage failed in noted in five patients. Peak pressures of 300 to postoperative ERC 139-398 (mean= three patients who required emergency mm Hg and greater were recorded in four 243) days after cholecystectomy. None had surgery and one died. Four died despite patients. Five patients had a frequency of common duct pathology either on pre- successful endoscopic drainage. Endo- contractions greater than 8/min and para- operative ERC or at operation. All had scopic duct clearance was achieved in 64 doxical responses were observed in five of cholecystectomy alone. Pre and postopera- patients, while 32 had elective biliary the patients given cholecystokinin. We have tive ERC of adequate quality were available surgery after the cholangitis settled with one shown for the first time prior to cholecystec- for scrutiny in 35 patients. The diameter of death. The overall mortality was 6%. tomy, abnormalities of sphincter motility in the common duct was measured at its widest Urgent endoscopic drainage of the biliary patients with acalculous biliary pain. point. Magnification was corrected for by system is indicated in patients with acute factoring down according to diameter of the suppurative cholangitis. endoscope measured on the same radio- graph. Gall bladder contraction in patients with The greatest diameter of the common Role of early ERCP and sphincterotomy in irritable bowel syndrome (IBS) duct measured 0(56-1-58 cm (mean+SD= acute biliary pancreatitis Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of GastroenterologyA A 1385 J W C LEiUNG, S C S CIIUNG, S D MOK, ANI) A K C showed increased CO, solubility: 1 13%zand enterohepatic circulation (EEHC) in mnan Li (Cotnbined Endoscopy Unit, Prince of 23% respectively for ursodeoxycholate and over 24 hours. This study aims to assess the Wales Hospital, The Chinese Universitvy chenodeoxycholate (both 150rmM) when EHC of bile using a portable giammna probc Hong Kong, Hontg Kong) Biliary diseases compared with buffer alone. and SeHCAT. Selected patients (n=8) are the commonest cause of acute We postulate that during administration were given 370 kBq oral SeHCAT. A pancreatitis. From November 1984 to of ursodeoxycholate, the radiolucent stone gamma probe wias secured ovcr McBurney's November 1986, we performed ERCP and is coated with ursodeoxycholate which point (terminal ilcum). Counts were sphincterotomy within same hospital admis- avidly solubilises CO, which will be in recorded every 15 s for 24 h on a Novo sion in 74 patients (M=20. F=54) with equilibrium with HCO3 and CO.,' CO3 Memolog 2A. Results were analysed by acute pancreatitis. the mean age was 56 will form an insoluble precipitate in the computer. There were peaks in counts of years (range 22-84). Ninety three per cent presence of Ca2' ions thus causing calcifica- two to four times the mean at between onc had hyperamylasemia; 76% had abnormal tion on the surface. Chenodeoxycholate and four hours post-SeHCAT ingestion, LFTs. ERCP was performed 7-3 days after treatment will coat gall stones with bile acid and these were followed by further peaks admission (range 1-25). CBD cannulation showing less avid CO, solubility and is less two to four hours later. Further waves then was successful in 70 (95(%O). Biliary diseases likely to act as a source of CO3 occurred with variable frequency, but of a were identified in 52 patienits (70(3°O): CBD lower amplitude. In half the patients the stones (13), IHBD stones (two), ascaris counts dropped below the mean and level- out sleep, suggesting that bile (four), gall stone (33). Three had dilated Methyl tert-butyl ether for common duct led during CBD only and eight had previous biliary stones: dissolution without radiological dis- ceased to circulate, and remained in the gyall there were con- surgery. No biliary pathology was identified appearance bladder. In the other half in 11 (including four with failed cannulat- tinuing large fluctuations in counts over- The pancreas was filled in 67 patients night, despite the fasting state. tion). J S DOOILEY, G KAYE, ANi) J A SUMMERFI-iLD and 15 had pancreatitic changes. No exacer- (Royal Free Hospital, London) Methyl tert- In conclusion, using an external gamnma bation of pancreatitis was observed. butyl ether (MTBE) dissolves cholesterol probe and SeHCAT labelled bile, we have Thirteen of the 15 patients with biliary shown that bile conltin1ues to circulate during gall stones rapidly, but common bile duct in some while in others it stones (CBD + IHBD stones) had sphincter- stones have resisted dissolution (Gastro- sleep subjects, otomy and nine had clearance of the CBD enterology 1986; 91: 1296). We have used does not. This subject merits further study, stones, two patients had residual intra- as major differences in the enterohepatic MTBE given through a nasobiliary or per- hepatic stones. Ascaris were removed endo- cutaneous transhepatic catheter to treat circulation may be relavant in a number of scopically in four patients. One patient with disease states such as bile malabsorption common bile duct stones (10-40 mm dia- a choledochal cyst and three with CBD diarrhoea and gall stones. meter) in four patients (age 43-87 years). stones (including two failed sphinctero- Increasing volumes (0-5-6 ml) were flushed http://gut.bmj.com/ underwent surgery with one death. tomy) in and out every 0(5 to one hour for six Thirty of 33 patients with gall stone under- hours. The session was terminated if the went cholecystectomy during the same cumulative loss of MTBE reached 10 ml. admission with no complication. Patients received one session a day for up to ILIVER 11 Early ERCP is safe in acute pancreatitis. four days. The maximum volume of MTBE The information obtained allows the given was 80 ml. There was no change in offending biliary pathology to be removed Longterm results of albendazole therapy of stone size on cholangiography in any within the same hospitalisation. hydatid disease: clinical and experimental patient. Duct clearance was however results on September 26, 2021 by guest. Protected copyright. achieved in three patients and in two of these, MTBE contributed to the success. In D I MORRIS, M J CiARKSON, K S RICHiARI)S, AND Ursodeoxycholate treatment and postulated the first, the composition of the stones, as [) IAYILOR (Department of Sulrgery, mechanism of calcification of previously judged by the resistance to basket closure, University Hospital, Nottinghaim) We have radiolucent gall stones had changed from rock hard to soft. In the previously reported encouraging in vitro, second, mechanical lithotripsy, previously animal model and clinical studies of the use J IIENDERSON (INI'RODUCED BY W PERCY- unsuccessful, crushed one of two large of albendazole in hydatid disease. Long- ROBB) (Dept of Pathological Biochemistry, stones. The remaining calculus (30 mm) term results, however, are unknown. Western Infirmary, (lasgow) Medical treat- passed spontaneously. Naturally infected Welsh sheep underwent ment of radiolucent gall stones is not new. In summary MTBE solubilises some radiology to identify cysts, followed by Chenodeoxycholate causes gastrointestinal common bile duct stones without any thoracotomy and needle puncture to con- side effects but not calcification of gall change in their cholangiographic appear- firm viability. Five shcep with live discase stones; ursodeoxycholate is palatable but ance. Radiological imaging alone is received albendazole 10 mg/kg by gavaige causes gallstone calcification after variable insufficient evidence on which to conclude for six weeks. Instead of immediate periods of treatment, precluding further that dissolution has failed. necropsy, as in earlier studies, we post- dissolution therapy. To investigate a poss- poned necropsy for six months to allow any ible mechanism for calcification during dis- viable material to recover. At necropsy only solution therapy we have measured carbon Enterohepatic circulation patterns in man one of five sheep was found to havc viable dioxide solubilisation by ursodeoxycholate protoscoleces. Electron microscopy showed and chenodeoxycholate solutions using D L STOKER AND J G WILLIAMS (Royal Naval complete destruction of the germinal layer tonometry against 5% CO, gas (pCO. Hospital, Haslar, Gosport, Hants) No data in almost all cysts, but some cysts from the 35-40 mm Hg). Both bile acid solutions have been published on variations in the single sheep with viable disease had a rela- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1386 The British Society ofGastroenterology tively normal germinal layer. We have now not improve survival and one shows that 139±145 omol/l compared with before treated 52 patients with albendazole. Of the rebleeding is not affected. We reviewed the urea. The serum urea fell rapidly after urea 30 treated in 1982-4 15 initially responded subsequent alcohol history and clinical was discontinued. to chemotherapy, six did not, and nine were course of 176 consecutive alcoholic cirr- Diarrhoea and vomiting commonly treated prophylactically before or following hotics after their first admission to the Royal accompanied urea therapy, requiring a surgery. Of those who responded five have Free Hospital with variceal haemorrhage. reduction in dosage. Encephalopathy subsequently recurred and two have been Exclusions: died within 30 days 66, absti- occurred in one patient. Oral urea acts as an retreated and have responded again. nent before bleed six, no follow up four, osmotic diuretic producing fall in weight We conclude that six weeks albendazole concomitant other liver disease 6-94 and improvement in hyponatraemia but therapy may not be adequate to kill all patients were followed up: median 20 without clinical benefit. hydatid cysts but that the majority do not months (range 2-97). Drinking was con- recur, and those which do may still be firmed by history, corroboration from rela- sensitive to therapy. tives and blood alcohol levels. Thirty Surgical management of bleeding oeso- remained abstinent and 64 continued to pageal varices: Warren shunt versus drink. Pugh's grading at initial presentation lienorenal shunt - 15 years' experience and length of follow up were similar in both Thyroid function as a prognostic indicator in in the cirrhosis groups. Mortality was 12/30 (40(%) J P A lODGE, A I D MAVOR, AND G R GILES abstinent and 23/64 (36%) in the drinkers. (University Department of Surgery, St Upper gastrointestinal rebleeding (exclud- R P BOILTON, L1 SHAPIRO, AND M S IOSOWSKY James's University Hospital, Leeds) Retro- (University Department of Medicine and ing peptic ulcers) occurred in 53OO (16/31) of spective analysis of patients undergoing Biochemistry, St James's Hospital, Leeds) the abstinent v, 75%o of the drinkers (48/64). lienorenal shunt (28) or distal splenorenal There was no significant difference in the (Warren) shunt (53) surgery (1971-1986) Various indices of thyroid function, includ- or rates between the ing rT3, rT,:T3 ratio and T3:T4 ratio, have rebleeding mortality revealed important predictive factors for two groups (logrank test), however, there survival, but showed no significant survival been proposed as prognostic indicators in was a trend towards a reduction in re- cirrhosis, but none gives a clear cut indica- differences between the two shunt groups tion of progress. Using an easily calculated bleeding after eight months of abstinence. over a period of up to 14 years. based Although abstinence probably has a bene- In 52 patients (64%) active haemorrhage index (Derived Thyroid Index, DTI), ficial this does not occur early enough on a single determination of the rT3:T3 and effect was the reason for operation and 17 of the T3:T4 ratios, we have prospectively evalu- to alter the prognosis after variceal bleeding 18 deaths (22% operative mortality) occur- ated 53 patients with cirrhosis of varied in alcoholic cirrhotics. red in this group. Patients in whom pro- aetiology, following patients until death or longed conservative resuscitation had been for 12 months. Nineteen patients were attempted fared worse (64% survival), as http://gut.bmj.com/ Child's grade A, 21 grade B and 13 grade C. Oral urea in the treatment of hyponatraemic did patients with poor hepatic reserve (Pugh Twenty one patients died and a further 14 ascites grade C: 32% survival). Twenty two deteriorated during follow up. The DTI was patients (27%) rebled within 30 days, 18 <2-5 in all 18 patients who remained stable P C HAYFS AND ROGER WILLIAMS (Liver Unit, after urgent shunts, and 12 died. Seven or improved, and was >2-5 in 32 of 35 King's College Hospital, London) The (110/o) of the longterm survivors have (91-40o) of patients who died or deterior- effect of oral urea in patients with cirrhosis suffered recurrent variceal haemorrhage, ated. Of 17 patients with a DTI >3-0, 14 and hyponatraemic ascites was studied in 10 with a clear relationship to shunt or portal (82-4%) died, whilst six of 15 patients patients. Conventional diuretic therapy was system thrombosis. Portasystemic encepha- on September 26, 2021 by guest. Protected copyright. (40%)) with a DTI between 2-5 and 3-0 died. discontinued once serum sodium fell below lopathy occurred in 13 survivors (20(%). Derived Thyroid Index was strongly corre- 130 mmol/l and patients randomised to We conclude that urgent lienorenal or lated with disease severity (r=0-703, receive three days of oral urea (20 G tid) distal splenorenal shunts for unremitting or p<0'00)1). One patient with a DTI value 'early', after the baseline 24 hours, and relapsing variceal haemorrhage are worth- <2-5 died, and a further two patients 'late', after a further three days without while. Selective decompression has been deteriorated. Thus, a DTI value of >2-5 treatment. Weight fell by a mean of 18±2 1 advocated as the precedure of choice, but gives a sensitivity of 91 4% and specificity of kg (SD) in all patients on urea and this the non-selective lienorenal shunt is easier 100% in the prediction of deterioration or reduction was significantly greater in those to perform and is equally acceptable in death during the following 12 months in randomised to urea early than those receiv- terms of postoperative morbidity. patients with cirrhosis, and provides a ing no therapy over the first three day simple, useful prognostic indicator. period (p=0-0)4). Serum sodium rose by 4-9±5-3 mmol/l from baseline on urea A medical/surgical team approach to the although the rise was not significantly management of acute bleeding varices Effect of continued alcohol consumption on greater compared with no therapy over bleeding and mortality after variceal three days. Urine output measured over the D MUTIMER, P D WRIGHT, J FREFMAN, t ILOOSE, haemorrhage three day period before and during urea AND 0 F W JAMES (Departments of Medicine, therapy increased from 718±202 ml to Surgery and Radiology, Freeman Hospital, P A MCCORMICK, I YIN, D SPRENGERS, N 1311+315 ml. Serum urea rose by 14-3±9-6 Newcastle Upon Tyne) While several con- MCINTYRE, AND A K BURROUGHS (Royal Free mmol/l mean from baseline and was signifi- trolled trials of different single modalities of Hospital School of Medicine, London) Two cantly higher compared with no therapy treatment for acute bleeding varices have large studies suggest that abstinence after (p=0 )03). Serum creatinine fell by 8-2+6-9 been carried out it seems likely that a variceal bleeding in alcoholic cirrhotics does [tmol/I and urine osmolality increased by treatment plan allowing the use of more Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A1387 than one method may prove more practical. that did not respond to therapy or received Inhibition of fatty acid oxidation as a cause We have evaluated the use of a 'multidisci- no therapy, and two progressed to cirrhosis. of ulcerative colitis plinary' treatment algorithm in the manage- Immuno-cytochemical studies confirmed ment of such patients. that in those clearing HBe Ag and HBV W E W ROEI)I(iER ANt) S It NANtF. (INTRODI)U( I.I) The treatment schedule is centred on DNA from the serum, HBc Ag and HBe Ag BY S C TRUEI OVE) (Department o'f SurgerY early endoscopy (by physician or surgeon were also lost from the liver. anid Cell Ph vsiology Laboratory, Univers'rity on a joint unit), with injection of varices at Cirrhosis/fibrosis (p<0 10) and abscence of Adelaide at Tlze Quleent Elizabethi endoscopy, or insertion of Sengstaken tube of orcein positive hepatocytes (p<0-05) Hospital, Adelaide, A ustralia) Studies have with subsequent endoscopic injection were the only factors to predict response. shown that ulcerative colitis is associated within 24 hours. If bleeding persists despite The studies support the view that success- with inhibition of fatty acid oxidation in initial injection (or if injection impossible) ful treatment of chronic HBV infection is colonocytes and that inhibitors of fatty acid patients are submitted to gastric devascu- associated with loss of hepatic as well as oxidation induced colitis in experimental larisation and oesophageal transection serum markers of HBV replication and is animals. The hypothesis was tested whether (GDOT) or percutaneous transhepatic followed by a reduction in hepatic inflam- a weak inhibitor of fatty acid oxidation embolisation (PTE) the latter for poor mation, preventing in some cases pro- (2-bromobutyrate, 4-mercaptobutyrate) in prognosis (modified Childs C) patients. gression to cirrhosis. conjunction with a selective stimulator of Ninety two patients seen for first time in fatty acid oxidation (sodium nitrite) could five years (1982-1986), had 131 emergency reproduce strong inhibition of fatty acid admissions with bleeding. Childs grade: oxidation in colonocytes similar to the bio- 27A, 22B, 43C (37 patients over age 60, 11 chemical lesion observed in human colitis. under age 20.) Isolated colonocytes of the rat were used to One hundred and thirty one bleeds, one measure fatty acid oxidation as "CO, death before treatment. Ninety one control- INFILAMMATORY BOWEL DISEASE POSIERS production from l-'4CJ butyrate. 4- led with sclerotherapy±tamponade--84 Mercaptobutyrate alone inhibited 14 5+ discharged, seven non-bleeding deaths. Faecal short chain fatty acids (SFA) in 2.40% and 2-bromobutyrate alone inhibited Thirty nine continued haemorrhage; 14 no ulcerative colitis (UC) and controls 31.4+1 3°/0 of fatty acid oxidation. Com- treatment died, 14 GDOT, 11 PTE. Of 14 bination of bromobutyrate and sodium GDOT bleeding was arrested in 12 (seven D A BURKE, P G R GODWIN, AND) 1 R AXON nitrite inhibited 73(0±8X5% of fatty acid discharged). Of 11 PTE bleeding was (Gastroenterology Unit, the General oxidation. Bromobutyrate inhibited keto- arrested in nine (seven discharged). Infirmary, Leeds and Department of Micro- genesis by 42 4±8+0(Y0 which was doubled Thus of haemorrhage biology, University of Leeds, Leeds) (89.3+6±5'(Y) in the presence of sodium 131 admissions the bulk of faecal controlled in 85%, discharge achieved in Anaerobes form the flora nitrite. The proposed hypothesis Was 75%. and the SFA are an end product of anaero- upheld from which it is suggested that an http://gut.bmj.com/ We conclude this 'team approach' offers bic metabolism. Little is known about the inhibitor of fatty acid oxidation from the with the best achieved in anaerobic flora in patients with UC. In vitro colonic lumen in conjunction with a stimu- results comparable work has shown a decreased ability to 'single treatment' centres and in a relatively lator of fatty acid oxidation, nitrite, known poor risk group. metabolise SFA by the colonic epithelium. to be generated from laminal cells arc To determine any disturbance in the needed to producc the biochemical lcsion equilibrium between production of meta- observed in human ulccrative colitis. bolic products and their absorption and Histological improvement after antiviral metabolism by the colonic epithelium faecal on September 26, 2021 by guest. Protected copyright. treatment for chronic hepatitis B virus levels of butyric acid (BA) and acetic acid infection (AA) were measured by head space gas Milk antibodies and circulating immune liquid chromatography in 16 patients with complexes in inflammatory bowel disease M G BROOK, 1. PETROVIC, J A MCDONALD, P J UC in relapse and 20 controls and results SCHEUER, AND H C THOMAS (Academic expressed as smol/g dry weight. In seven J MAIN, tl MCKEN/IFI, C R PINNINGTON, ANt) Department of Medicine and Department of cases SFAs were assessed before and after t) PARRA IT (Department of Medical Micro- Histopathology, Royal Free Hospital and treatment. Colitic faecal BA mean 149 and biology, Ninewells Hospital antd the Depart- Medical School, London) Sequential liver AA mean 438-5 Fmol/g were significantly ment of Medicine, Kings C(ross Hospital, biopsies taken from 50 patients with chronic higher than control BA, mean 28 ,tmol/g Dundee) IgG and IgA antibodies against hepatitis B virus (HBV) infection under- and AA mean 64-5 ftmol/g (p<0-005). whole milk and certain milk antigens were going therapy with AraAMP or alpha inter- There is a significant correlation between estimated by an ELISA in 44 patients with ferons were compared with biopsies from 25 BA and AA levels in controls p A 1 388 TI-ue British Societx oJ Gastroenterologv mean=47 ,ug/ml, range 0-1000) and ulcera- Macrophage and lymphold subpopulations andL 12 weeks after a defunctioning tive colitis (IgG mean= 192 [tg/ml, range in the granulomata of Crohn's disease ileostomy. Fhe elffect of restorationi of 0-3000; IgA mean=42 .tg/ml, range 0-660) intestinal continuity was also assessed in groups when compared with controls (IgG Y R MAFIlDA. S PATEH, K WuJ, AND I) P JE-Wi-i I. Crohn's disease (CD, n=9) and controls mean=83 ftg/ml, range 33-210; IgA (G(astroentterology U,iit, Radclitf (n=7). Predeifunction GS activity was sig- mean=8 Rg/ml, range 0-75). There was a Itnfirmary, OvJord) Granulomata arc a nificantly increased in the ICD group com- significant correlation between milk anti- characteristic feature of Crohn's disease. pared with controls (34X8±4-5; 22 9±3+4, body and CIC values for IgG in Crohn's This study describes the distribution of p<0-05). Postdefunction - there was no disease (r=0-78, p<0-01) but not in ulcera- macrophage and lymphocytc subpopula- change in GS activity in the control group tive colitis (r=-028, p>0.05). The correla- tions in the granulomrata of four paticnts but ICD activity had fallen significantly tion between milk antibody and CIC values with Crohn's disease (thrce ileall, one fronm 34-8±4-5 to 19-2±3-4 at six weeks, for IgA was significant for both Crohn's colonic). and 16-4±4-6 at 12 weeks, p<0()-. Crohn's disease (r=0-82, p<0.0l) and ulcerative Tissue was snap frozcn and 4 u sections proctitis activity had fallen significantly colitis (r=0-54, p<0-0l). stained using the peroxidasc and alkaline from 28X6+3(0 to 16-2+2-5 at six weeks, The observed correlation between CIC phosphatase techniqucs, singly or in com- p<0(l0. On restoration of intestinal con- and food antibody supports the possible bination. Acid phosphatase (ACP) and tinuity, there was a significant increase in association between CIC and food antigen non-specific estcrase (NSE) stiaining was CD from 14 7+2-5 pre-operatively to processing. In inflammatory bowel disease also performed. Monoclonal antibodies 25-5±3-7 at two weeks, p<0-0l but no increased absorption of food antigens used: RFD1 (interdigitating cells), RFD9 change in the control group. These results may generate high levels of CIC, although (epithelioid cells and tingible body macro- suggest that a luminal factor significantly their pathogenetic significance remains phages), RFD7, EB I1 (tissue macro- stimulates glycoprotein synithesis in Crohn's uncertain. phages), 3C10, Y1/82A, UCHMI (mono- discase. This finding supports the role of a cytes and macrophages), 3G8 (Fcy receptor toxic faecal component stream in the patho- on polymorphs and some macrophages), genesis of Crohn's disease. Colonic lymphocyte subpopulations in CR3/43 (HLA-DR), BT3/4 (HLA-DQ), inflammatory bowel disease IL2R (interleukin 2 receptor), T3 10 (CD4), DK25 (CD8). Personality in inflammatory bowel disease to chronic M C ALIISON, 1. W POULTER, A P DHILLON, ANI) The epithelioid cells and giant cclls were (IBD): primary, or secondary R E POUNDER (Royal Free Hospital, London) strongly RFD1I+, RFD9+, EBII+, illness? Although lymphocytic infiltration is a well- 3C1()+, YI/82A+, CR3/43+, BT3/4+-, known feature of ulcerative colitis (UC) and ACP+, NSE+, and moderately 3G8+, I) A F ROBERI'SON, J RAY, AN[) I DIAMONI) Crohn's colitis (CC), the location of T and B UCHMI+, and IL2R+. RFD7+ cells (Departments ofJ Medicine atnd Social Statis- cell subtypes and their state of activation (weakly ACP+, NSE+) only occurred at tics, UniversitY of Soutlihampton, Southamp- http://gut.bmj.com/ have not been fully characterised immuno- the periphery of the granulomata. Lympho- toni) The high prevalence of personality intro- histologically. Frozen sections of colonic cytes within the granulomata were mainly traits of neuroticism. anxiety and is well in but biopsies or resections from five patients CD4+. CD8+ cells were few and scattered version described IBD, to disease, or a with active UC, 13 with Crohn's disease mainly at the periphery in association with whethcr these arc secondary is unknown. We (five with colitis) and seven controls were RFD7+ macrophages. This distribution is primary phenomenon, and stained with a panel of monoclonal anti- in contrast with that seen in schistosomal havc measured the Hospital Anxiety bodies using an immunoperoxidase tech- intestinal granulomata. Depression scale (HAD) and Eysenck nique. The antibodies were RFT Mix Crohn's granulomatia comprise cpithe- personality inventory (EPI) measuring on September 26, 2021 by guest. Protected copyright. (recognising T cells), RFB Mix (B cells), lioid cells (RFD9+, RFD7- ) intimately neuroticism and extraversion on a linear Leu 3A (helper T cells), SN 130 (subsets of associated with CD4+ lymphocytes. scale (1-24) in 8() IBD patients, in 22 newly referred patients before the diagnosis of T and B cells) and anti Tac (a marker of T Epithelioid cells are 11 2R+ and appear to cell activation). The histologically normal be activated. IBD, and in 4(0 controls (Diabetics attend- sections and those from patients with CC ing a clinic). Inflammatory bowel disease displayed marker variations in mucosal T patients were more neurotic (mean EPI cell populations that did not correlate with 12-(0 9, p<0.05) and less extroverted (9 8 v disease activity. However enlarged basal Mucosal glycoprotein synthetase in Crohn's 12-0, p<0-05) than controls and these traits lymphoid aggregates with wide submucosal disease: a protective mechanism? are prcsent before diagnosis (EPI neuro- extension were found in all CC sections, and ticism 13 v 12, EPI extraversion 9-8 v 9-8, these aggregates contained many Tac M C WINSIET, VAILERIEi POXON, A Al.l.AN, ANI) NS). In established disease, depression positive cells. By contrast, marked mucosal M R B KEIGHili.Y (The Genieral Hospital, correlates strongly with disease activity and infiltration with all T cell subtypes, includ- Birmin,gham) Glucosamine synthetiase introvcrsion with disease duration. Patients ing many Tac positive cells, was found in the (GS) is a rate limiting enzyme in mucosal were aware of a close link between stress UC sections. B cells were present in glycoprotein synthesis. Increased rectal GS and disease activity: 59 identified a stressful lymphoid aggregates but not in the mucosal activity has been reported in patients with life event which they believed precipitated infiltrate. ileal Crohn's disease (ICD) which may the illness. Neuroticism and introversion These observations offer evidence that represent a protective responsc to toxic are common in IBD patients and these traits the immunopathogenesis of UC and CC luminal factors. To test this hypothesis, arc present before diagnosis. Depression both involves a cell-mediated immune rectal GS activity was measured in ICD occurs predominantly in those with active response but show marked differences in (n= I 1), Crohn's proctitis (CFP n= 11) and a disease, and introversion increases as the cellular localisation. control group (n= 11) before and two, six, disease progresses. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroeniterology A 1389 Smoking and sugar intake are separate but clinical activity indices for Crohn's disease Although 38 of 51 features had agree- interactive risk factors in Crohn's disease (CD) such as CDAI (Best et al). Al (van ment measures significantly better than Hees), SI (Harvey and Bradshaw), Oxford expected by chance, only three (neutrophil B KATSCIIINSKI, R F A l.OGAN, M E)MOND, ANt) Score, and laboratory parameters: ESR, infiltration of crypt epithelium, neutrophils M J S LANGMAN (Departments of' Thera- serum albumin, orosomucoid, C-reactive in lamina propria and Langhans giant cells) peutics anid Communit AIMedictine aIltd protein, a,-antitrypsin (at -AT) faecal con- had Kappa values of 0-4 or grefater, such Epidemiology UniversitsV of' Nottingham, centration, and ca1-AT clearance. Twenty values being considered to show fair to good Nottingham) Previous studies have consist- eight CD patients (18 F, age 16-60 years) agreement. Thus, the vast majority of ently found a strong positive association were studied. Nine had colonic involve- features had Kappa values indicating poor between sugar intake and Crohn's disease ment, 18 had small bowel localisation, one agreement beyond chance. The range of (CD) and recently others have found a patient colonic and small bowel involve- agreement amongst the 45 observer pairs strong association between smoking and ment. Indium-llI activity of faeces samples over the final diagnosis was 65-76%). Only CD. As sugar intake and smoking are often were measured in a gamma counter and normal biopsies had a Kappa value greater linked we have investigated this relation- expressed as per cent of the injected dose. than 0-4. Those from patients with ulcera- ship in 104 CD patients and 153 matched The median was 8% (range 0-.15-50%) for tive colitis and Crohn's had Kappa values of community controls. Data on added sugar colonic involvement and 0)*75% (range 0(03- 0(3 and 0)2 respectively. intake (AS), confectionery consumption 2 10%) for small bowel disease. These results suggest that there is con- and smoking habits were obtained by postal No significant correlation was found siderable room for improvement in the questionnaire. Relative risk (RR) estimates between Indium- Ill FE and any of the four reliability of colonic biopsy interpretation (95%o confidence limits) were derived using activity indices used in this study, neither and could probably be achieved using more Mantel-Haenszel analysis. Added sugar for colonic nor for small intestine or for both exact definitions of morphological features intake and smoking were associated with combined. Indium-11 FE however was and diseases. one another. After adjusting for AS smok- positively correlated with orosomucoid ing still showed a significant association with (r=0-53; p<0-05), al-AT faecal concentra- CD with a RR of 1-8 (1-04-3-2). Equally tion (r=0-64; p<0-05), a,-AT clearance after adjusting for smoking AS was also (r=-039; p<0-05), and negatively corre- Tc-99m-HMPAO labelled white cell imaging strongly associated with CD in a dose- lated with serum albumin (r= -0-52; - a new technique for the dynamic assess- response pattern (x5=7-7; p<-*025) but this p<0)05). ment of inflammatory bowel disease relationship was only evident in never and None of the studied activity indices reflect ex-smokers. For never and ex-smokers the accurately the degree of inflammation as A H M tlEAGERTY, D C COSTA, D UlI, J M - RR's associated with no AS, <50 g/day and assessed by Indium-11 FE. Objective CLARKE, S R CAIRNS, P J EL.l, AND N I MCNEIIt >50 g/day were respectively 10, 1*8 (0X-8 laboratory parameters should be used in (Department of Gastroenterology and 3-0) and 4.6 (2-0-11) (X =12-1; p<0-005) studying activity of CD. Indium-111 FE is Institute of Nuclear Medicine, Middlesex http://gut.bmj.com/ and for smokers 1-0, 0(8 (0-2-2.7), 1-1 therefore a good parameter which can be Hospital, London) The assessment of (0.4-3 1) respectively. The AS relationship used in the evaluation of new forms of activity and extent of inflammatory bowel was supported by a separate association treatment. disease (IBD) by endoscopy or radiology is with confectionery consumption with the time-consuming, uncomfortable, often RR's of never or < monthly consumption, technically difficult and open to misinterp- monthly, and weekly or more often being Observer variation in the histopathological retation. Using tracer labelled white cells respectively 1-0, 1-7 (0-7-4-0) and 3-0 (1-2- assessment of rectal and colonic biopsies for dynamic imaging to assess the extent of 7-5) (X2 =6-8; p<0.05). These findings inflammation has much improved the situa- on September 26, 2021 by guest. Protected copyright. indicate that while smoking and AS are A 'FHEODOSSI, D J SPIEGELHALTER, J JASS, tion. individually associated with CD combined J FIRTH, M DIXON, M IlEADER, D LEVISON, Tc-99m-Hexamethylpropyleneamincox- exposure results in no further increase in R lINDLEY, I FilIPE, A PRICE, N A SHEPHERD, ime (Tc-99m-HMPAO) has been identified risk, suggesting that they may operate S THOMAS, AND H 'I'HOMPSON (The Mayday as a useful tracer for white cells. This was through a common mechanism. Hospital, MRC Biostatisticy Unit Cam- simultaneously compared with the estab- bridge, Departments of Pathology, St lished Indium-IlI -oxine (In-lI1) labelling Marks, Westminster, St Batholomews, technique in 12 patients with known or Guys, Northwick Park Hospitals, Leeds suspected IBD at one, four, and 20) h using Are clinical activity indices helpful in assess- General Infirmary, and The General appropriate energy windows for the iso- ing active intestinal inflammation in Crohn's Hospital, Birmingham) If skilled histo- topes. One patient had scans seven days disease? pathologists disagree over the interpreta- before, and 60 days after resection of ileal tion of the same biopsy this leads to diagnos- Crohn's disease as well as imaging of the G 1' CRAMA-BOHIBOUTH, I BIEMOND, A S PENA, tic error. The aim of the present study was resected specimen. If W VERSPAGI:'r, I I WETERMAN, AN[) C B H W to determine the magnitude of variation This study showed that both isotopes LAME.RS (Dept Gastroenterology and amongst ten observers with a special produce identical leucocyte distributions in Hepatology, University Hospital Leiden, interest in gastrointestinal histopathology, these patients, ranging from nothing to The Netherlands) Quantification of the who independently interpreted the same extensive intestinal uptake in small bowel faccal excretion (FE) of iv administered biopsies for morphological features which Crohn's disease. The resolution with Tc- autologous Indium- 111 tropolonate label- may discriminate between patients with 99m-HMPAO was uniformly better than led granulocytes is a reliable parameter of Crohn's disease (n=24), ulcerative colitis with In-1il. Scans of the operative speci- bowel inflammation. In this study we corre- (34), and normal subjects (18). More than men showed localisation specific to the lated 24 h Indium-l 11 FE with several 50 000 items of information were evaluated. active disease. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1390 The British Society ofGastroenterology Assessing the extent of IBD with Tc-99m- ment of Pathology, University of Leeds, 48 5-ASA for analysis. Groups were com- HMPAO labelled white cells has the princi- Leeds) Patients with UC harbour adhesive parable for age, sex, duration, and extent of pal advantage of better resolution without E coli in their colon. This double blind trial disease. missing active disease and utilising a more was performed to determine whether eradi- Relapse rates at 48 weeks were SSZ readily available tracer. We believe it is the cation of E coli is of benefit. Eighty four 38-6% (95% confidence limits 24-54%) and standard isotopic method of choice in patients with UC in relapse were random- 5-ASA 37.5% (95% confidence limits 24- assessing IBD, until an in vivo labelling ised to seven days tobramycin (T) 120 mg 53%) X2=0-01, p>0-90. Mean time to technique is widely available. tds or placebo (P) as an adjunct to steroid relapse and relapse severity were similar in treatment. Patients were assessed by the two groups. Headaches and upper clinical and histological scoring at entry and gastrointestinal symptoms were less Effects of prednisolone, sulphasalazine, endpoint (EP) (21 days for inpatients, 28 common in the 5-ASA than in the SSZ 5-aminosalicylic acid and indomethacin days for outpatients). Culture for faecal E group. Haemoglobin concentration rose on prostaglandin E2 and leucotriene B4 coli was undertaken at entry, seven days and MCV fell during 5-ASA treatment, production and EP. Tobramycin and P groups were folate levels, however, remained well matched for age, sex, extent of disease, unchanged. Delayed release 5-ASA is as effective as J J KEATING, W J MAXWELL, FP HOGAN, AND length of history and duration of relapse. P W N KEELING (Dept of Clinical Medicine, Bacteriology results were unsuitable for SSZ in maintaining UC remission and has Sir Patrick Dun Research Laboratory, St analysis in 6 T and 7 P. In the remainder fewer side effects. James' Hospital, Dublin) Sulphasalazine seven day assessment showed that E coli had been eradicated in 77% T and 8-8% P, (S/S) and 5-aminosalicylic acid (5-ASA) Combination antimycobacterial chemo- decreases the frequency of relapse, whilst p<0-0)01 and the strain changed by EP in 91% T and 13-8% P, p 5-ASA increased PGE, concentration salicylic acid (5-ASA) and sulphasalazine Indium scanning, colonoscopy, histology on September 26, 2021 by guest. Protected copyright. (44-6+11-6, n=7, 48-5+10-8, n=7 v (SSZ) as maintenance treatment of ulcera- and radiology before, three and nine 15-4+3, n=7, p<0.025, cells cultured with tive colitis (UC) months after treatment. Three patients S/S v 5-ASA v control cells). Again neither have not yet completed initial assessment. drug significantly altered LTB4 production. S A RILEY, V MANI, M J GOODMAN, AND A Treatment failed in two patients because of The results suggest that pharmacological TURNBERG (University Dept of Medicine, non-compliance although one of these had manipulation of PGE2 and LTB4 biosyn- Hope Hospital, Salford, Leigh Infirmary, responded before withdrawal. Eleven of 12 thesis may play a different role in the and Bury General Hospital, Manchester) patients responded, mean initial CDAI of management of acute and chronic IBD Many patients with UC are denied the 275±99-7 (ISD) falling to 176+93 within hence Pred decreases PGE, production beneficial effects of SSZ as side effects are one month. In five patients with severe during an acute episode and may decrease common. As most of these are related to the intractable CD refactory to conventional the inflammatory reaction whilst S/S and sulphapyridine component of the drug we therapy, response was dramatic and 5-ASA increase its synthesis and hence have assessed the efficacy of a delayed- impending surgery was avoided. Although modulate the chronic immune response. release 5-ASA preparation in maintaining disease course after cessation of chemo- UC remission. therapy is not yet known, these early results One hundred patients (51 M:49 F, aged would support a wider study of this Oral tobramycin improves the outcome of 20-78 years) with quiescent UC were approach in the clinical management of CD. acute ulcerative colitis (UC) randomly allocated to either enteric coated The consistency, and in some cases, scale of SSZ or equivalent dose 5-ASA in a double- the response further suggests that patients D A BURKE, S A CLAYDEN, M F DIXON, A T R blind 48 week trial. Eight patients were with otherwise uncomplicated severe CD AXON, AND R W LACEY (Gastroenterology withdrawn (four non-attendance, two non- should not be subjected to major surgical Unit, The General Infirmary, Leeds and compliance, one stomatitis (SSZ), and one resection before a trial of antimycobacterial Department of Microbiology and Depart- inappropriate inclusion) leaving 44 SSZ and chemotherapy with multiple drugs. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1 39 1 Fish oil for inflammatory bowel disease? activity score (DAS) combining subjective Extensive colonic disease (n= 145): 22% symptoms with changes in haemoglobin, were treated conservatively. Of those P J PRICHARD, T K DANESHMEND, J E WILLIARS, ESR and serum albumin. Remission was undergoing resection (mean interval 6.7 B FILOPOWICZ, D L[ESER-SMITH, AND C J defined as reduction in DAS-4, and steroid years) the cum-re-op was 48%, 61%, and HAWKEY (Departments of Therapeutics, withdrawal within three months with no 79% at 5, 10, and 15 years. Currently 92% University Hospital, Nottingham) Leuco- evidence of relapse for a further month. At of survivors are well although 45 (41%) trienes synthesised from the precursor randomisation (induction phase) both have evidence of recurrent disease and 78 eicosapentaenoic acid (EPA) - that is, groups were similar for site of disease (large (67%/) have a permanent stoma. Only nine LTB5, appear to be less pro-inflammatory bowel 25, small bowel 24), number of patients are symptomatic. than those derived from arachidonic acid - previous relapses, median DAS (CL 10, PL In total there were 36 related and 24 that is, LTB4. Administration of fish or fish 9-5) and median initial steroid dosage (45 unrelated deaths. The commonest causes of oil high in EPA may thus be beneficial in mg). Twenty seven patients (55%) achieved related death were sepsis (16), electrolyte inflammatory conditions such as ulcerative remission (median DAS: 1) and there was imbalance (seven), and cancer (six). colitis. We have investigated the bio- no difference between the two groups (CL The longterm prognosis is good even chemical consequences, safety and efficacy 15: PL 12, p=NS). In the second phase of though the incidence of reoperation for of this dietary approach. Consumption of the study (maintenance phase) these 27 recurrent disease is high. Most patients are fish oil (Hi-EPA, 20 ml/day, giving 4 grams patients continued to receive either CL or currently well although many have to accept of EPA per day) for one month caused an placebo for a further 8 months or until a permanent stoma to achieve this status. increase in cell membrane EPA from relapse, defined as an increase in DAS-8. 1-17±0-16% (mean+SE) to 3-35+0 34% of Eighteen patients (38%) had no further total fatty acids (GC assay), a 55% (95% relapse (CL 12: PL 6, p=NS) and success- Segmental colectomy for Crohn's disease of confidence limits: 40-70%) decrease in the fully completed the trial. Side effects were the colon detectable amount of the pro-inflammatory minor and consisted of skin rash (CL 3) and compound LTB4 (HPLC assay). Produc- increased pigmentation (CL 12, PL 5). H A ANDREWS, A ALLAN, C J HILTON, M R B tion of the less inflammatory compound In conclusion, clofazimine was neither KEIGHLEY, R N ALLAN, AND J ALEXANDER- LTIB5 was detectable in only four of 12 effective in inducing or maintaining remis- WILLIAMS (Gastroenterology Unit, General subjects under control conditions, but was sion and is further indirect evidence against Hospital, Steelhouse Lane, Birmingham) It present in eight subjects after fish oil. In an a mycobacterial aetiology for Crohn's is now clear that limited resection is appro- open pilot study, five subjects with severe disease. priate for small bowel Crohn's disease par- colitis resistant to steroids were treated with ticularly as the risk of re-operation is not the addition of Hi-EPA, 20 ml/day, and affected by histological evidence of involve- azathioprine (2 mg/kg/day) to existing ment at the resection margins. This study http://gut.bmj.com/ therapy. After three to four weeks, all had An audit of the management of Crohn's colitis evaluates the place of limited resection in improved and four were in remission. Fish colonic disease. oil caused no significant adverse effects and H A ANDREWS, P LEWIS, J ALEXANDER- Thirty six patients underwent segmental its use in inflammatory bowel disease colonic resection for Crohn's colitis warrants further investigation. WILLIAMS, M R B KEIGHLEY, AND R N ALLAN (Gastroenterology Unit, The General between 1944 and 1986. None of the 29 Hospital, Birmingham) An audit of the long patients undergoing segmental resection term outcome among 361 patients with and primary anastomosis had anastomotic dehiscence. There were two postoperative Controlled trial of clofazimine in Crohn's colonic Crohn's disease followed between on September 26, 2021 by guest. Protected copyright. disease 1944-1986 (mean follow-up 13-3 years) has deaths from septicaemia in elderly patients. been undertaken in an attempt to define At 10 years the cumulative re-operation N H AFDHAL, A LONG, J LENNON, J CROWE, optimal management. rate was 60% compared with 48% after AND D P O'DONOGHUE (Dept of Gastroenter- Right sided disease+ Distal ileum (n = 85): colectomy and ileorectal anastomosis, and ology, St Vincent's and Mater Misericordiae 11 % were treated conservatively. The 24% after panproctocolectomy. There was Hospitals, University College, Dublin, remainder underwent resection (mean a significantly higher recurrence rate in the Ireland) The aetiology of Crohn's disease interval from diagnosis 3-8 years). Cumula- segmental colectomy group (X' p<0-(X)8) remains obscure and an infective agent, tive re-operation rates for recurrent compared with the recurrence free interval perhaps an atypical mycobacterium, has disease (cum-re-op) were 19%, 40%, 51% curves following total colectomy with been proposed. A preliminary study with at 5, 10, and 15 years. Eighty per cent of ileorectal anastomosis or panproctocolec- clofazimine (CL), a broad spectrum anti- survivors are symptom free although 29% tomy. mycobacterial agent with both anti- have radiological evidence of recurrent There was no apparent functional or inflammatory and neutrophil stimulating disease. Only three patients are currently nutritional advantage from retaining properties, was favourable but has unwell. residual functioning colon following local remained unconfirmed (Gut 1982; 23: 449). Left sided disease (n=131): 37% were colonic resection. We now rarely recom- Therefore to determine the effect of CL on treated conservatively. Of those under- mend segmental colectomy for colonic inducing disease remission, 49 patients (34 going resection (mean interval six years) the Crohn's disease. F, age 28±13 years) with active Crohn's cum-re-op were 39%, 50%, and 55% at 5, disease were randomised to receive cortico- 10, and 15 years. Ninety five per cent of steroids and either CL 100 mg (25) or survivors are currently well. Fifty five per Sustained epithelial proliferation after matching placebo (PL, 24). Disease activity cent have a permanent stoma and 45% faecal diversion for Crohn's disease objec- was monitored using a modified disease radiological evidence of disease. tive evidence of mucosal recovery Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1 392 The British Society ofGaistroenterology M C WINSIL[I, [)ENISE YOUNGS, A ALtLAN, AND) vaginial fistulae causc little local disahility Nottinghaflm) Previous studies based on M RB KEHitLEUY (The General Hospital, and cain be mainaged symptomatically hv hospital diagnosis of symptomatic patients Birmingham) Faecal diversion for Crohn's scrupulous hygiene, they do not heal on hatvc estimatcd the prevalenice of inflammia- colitis frequently produccs clinical remis- conservative measures and in time the tory bowcl diseaise (IBD) to be betwecn sion but there is no objective evidencc of miajority develop such severe bowel symp- ) In Nottinghalm the exist- mucosal recovery. The effect of faccal toms that resection, usualily proctectomy. is ence of a screening programme for color- diversion may be mcdiated by changes in required. As two patients in this group ectal cancer hats provided an opportunity for mucosal cellular kinetics. To test this hypo- developed cancer in the fistula track, we the detcction of apparently asymptomatic thesis, the cell birth rate (crypt ccll produc- would now recommend early consideration cases of IBI) and the prevalence to he tion rate - CCPR) ol rectal mucosai in of radical surgical thcrapy for cntcrovaginal assessed. patients with ileall Crohn's diseaisc (ICD, fistulac in Crohn's diseasc. Between 1983 and 1987, 37 000 indi- n= 1), Crohn's proctitis (CP, n=9) and a iduals aged 5(t-75 years have been offered control group (n= 10) was mceisured beforc faecal occult blood tests (FOBT), either ztnd two, six, and 12 weeks after defunc- three or six Hilemoccult or Feca as Studies on the anorectal function in ulcera- davy EIA, tioning ileostomy. Crypt cell production tive colitis (UC) a screening test for colorectal neoplasia. rate was assessed by an in vitro stathmo- Seventeen thousaind nine hundred aind kinetic method. Thcre was no significant thirty individuals have completed the S S ( RAO, N W Ri At), ANt) C I) 11O DSWORITit difference in pre-diversion levels of CCPR FOBT's and of these 481 have been posi- (Sub-Del)e (irtnen oJ F/ontionla Glastro- (control =34±10(), ICD =28±()06, CP= tive. Colonic investigtation in these indi- intiestina(il Pl/iysiOlogy5 a(1( N Uitritiotn, Roval 2.4+).9). Post-diversion therc was a signifi- Hallnmshire Hospitll, She ffield) The patho- viduals revealed eight patients with pre- cant reduction in the CCPR of the control viously undiagnosed IBD; five patients had physiology of the howel disturbance if UC group at two weeks (I12±0)4, p<0()05) but total ulcerative colitis, one proctitis, and wats assessed by measuring anorectll not at six weeks (1 7±0()4) or ait 12 wceks two Crohn's disease. Two further patients pressures at multipie sites under basal coIn- (3.3+ 1.5). There was no significant change ditions, during hbilloon distension of the with ulcerative colitis were identified who in CCPR of the ICD or CP group at two had been lost to follow up for 25 and 45 rectum aind during rectal infusion of saline weeks (ICD=20()±0(7; six years respectively. The prevalence of CP=3±()8(),8) in 29 patients with UC and in 30( norimll weeks (ICD=2-1_±0(8; CP= 38+ 1 -)) or 12 ulcerative colitis in this population was at sublects. Resting and squeeze sphincter weeks (ICD=2 1±0)5; CP=2 1±16). The least 446 /100)00(95)(o Cl II 2-78 1) while pressures were similar in the three groups. sustained proliferation rate after diversion that of Crohn's disease wats 11 2/100(0)00 [Ihe lowest rectal volume that could be in Crohn's disease compaired with the sig- (95%, Cl (0-446). Thus the combined pre- perceived, the volume required to induce a nificant fall in the control group may repre- valence of IBD wias 56/100 000) and this data desire to defaccate and the maximum toler- sent a regenerative mechanism promotiing suggests that current epidemiological able rectal volume were all lower in alctive http://gut.bmj.com/ epithelial repair. This response suggests colitics thian quiescent colitics (p<() ()()I) studies underestimate the UK prevalence of that a toxic faecal component may per- and controls (p<0(00 I). The rectal volume IBD by at least 30%o. petuate the inflammatory process in required to cause a sustained anal relaxa- Crohn's disease. tion was lower in active colitics (p<()0()5) than controls. During balloon distensioni both initial aind steady state rectal pressures Enterovaginal fistulae in Crohn's disease were higher in patients with active thain B\ASKI SCI1NCt quiescent colitis or controls (p<0(05). on September 26, 2021 by guest. Protected copyright. FRANCOISE I1EYEN, M WINStLET, 11 ANDREWS, During resting conditions, rectail contrac- Coeliac sprue (CS): the sequence of immuno- tions were less in R N AllAN, M R B KUIGHIU.Y, AN) J recorded frequently active pathological events after rectal gluten AlrEXAND)UR-WiILLIAMS (The Gen-ieral colitics (12 5'Y(0) than in quiesccnt colitics challenge Hospital, Birmingham) Conservative (31 5'0o) and controls (37(%). During saline management of enterovaginal fistulae in iniusion, the amplitude of rectal contrac- 1) E ILOFT, P T CROWIF ANU) M N MARSH Crohn's disease has been advocated for less tions wals higher in colitics compared with (D)epartment of Medicinle, Hope Hospital, symptomatic patients. We reviewed 27 controls and the volume of silinc retained Solfort, Manchester) To document the patients with spontaneous enterovaginal wats lower (p<0(001 ). In conclusiol, the changes in rectal mucosal structure, epithe- fistulae complicating active disease, seen frequent and urgent defaecation in aIctive fial lIymphocyte populattions and mast cells between 1970 and 1987. Ten required early colitis is relatted to a hypersensitive rectuimi tollowing local gluten challenge in CS operaition, including three proctectomies. that is morc reactive to distension and patients and controls (C). Conservative management healed no listula induccs .a more pronounced sphincter Biopsies were taken pre-, and at 1, 2, 4, 6. in 16 patients. During this long follow up relaxation. 8, 12, 24. 36, 48, 60, 72, 96 hours post- (two months-35 years), six patients challenge, with either 2 g FF3 (n=9 CS/6 C) required a panproctocolectomy. one or 500 mg ji lactoglobulin (n=6 CS/6 C) patient had a total colectomy for megacolon Detection of asymptomatic inflammatory instilled rectally. Each biopsy was quanti- and one had a defunctioning stoma for bowel disease while screening for colorectal fied by computerised image analysis for: (1) stricture. Two symptomatic patients died of cancer lamina propria volume (LPV), surface, and unrelated causes, four are still mildly symp- crypt epithelial volumes; (2) absolute crypt tomatic. Two patients died of malignancy K ( BAIIANIYNI., .1 I MAYBIJRY, (G PYIF, epithelial lymphocyte population (CEL). arising from within the chronic entero- ( MAN(iIAM, ANI) J I) IiARDCASTITI (Depaort- (3) Epitheliil lymphocytes were pheno- vaginal fistula. Although some entero- itietit of Sutgery,% UniversitY Hosifital, typed with monoclonal antibodies, (4) Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 139)3 vascular permeability monitored with Different effects of VIP and PHI on intestinal was used to characterise these tumours. The peroxidase-anti-fibrinogen antibody and (5) adenylate pituitary growths lfiled to show immuno- mast cell structure assessed by EM. reactivity to antisera against pituitary There was a marked rise in OKT8+ J A SMITIH AND R (G l ON(G (Medical Research hormoness vaisopressin or at wide rainge of suppressor-cytolytic CEL maximal at six Centre. Cit'v Hospital, Noltiglhatn) Vasoac- other hormonall peptides and general hours (115% increase) in CS (p<0)-01). tive intestinal peptide (VIP) and peptide neuroendocrine mairkers. The endocrine Lamina propria volume increased at one histidine isoleucine (PHI) are closely tumours ol the paincrcas showed immuno- hour and significantly so by six hours related regulatory peptides. Vasoactive reiactivity lor insulin with occasional (p A 1394 The British Society ofGastroenterology Activated complement is cytotoxic to diuretic therapy and receiving 40 mmol of caincer markers (Gut X1987: 28: A372). We isolated rat hepatocytes sodium/day. The cirrhosis was alcohol have now sequenced its carbohydrate side induced in all but two cases, but no subject chains by sequential degradation and lectin A J K WILLIAMS, S K MOUI E, J I) MCGIlVAN, AND consumed alcohol within one wcek of this binding. R E BARRY (Department of Medicine, Bristol study. Values wcre median (rangc) and The undegraided piancreaitic cancer glyco- Royal Infirmary, Bristol) Activated comple- comparison was by Mann Whitney U test. protein binds the lectins peanut agglutinin ment forms a terminal membrane complex Thus the clearance in plasma NA in (PNA, gal 1-3 gal NAc binding), ulex which can lyse susceptible cells. Comple- cirrhosis+ascites represents a marked europacus I (UEA 1, fucose), limax flavus ment activation has been shown to occur in increase in global sympathetic activity (LFA, sialic acid) and whecat germ agglu- vivo in PBC, and we have shown that rather than any reduction in clearance. This tinin (WGA, sialic acid, NAc glucosamine). acetaldehyde modified hepatocyte mem- could partly explain both sodium retention Serum containing the marker was electro- branes will activate complement and this and renal vasoconstriction, and favours the phoresed (SDS-PAGE. 2-1604,) and blot- may be hepatotoxic in alcoholic liver 'underfilling' theory of ascites formation. ted onto nitrocellulose paper. The blot was disease. We have therefore studied the subjected to mild acid hydrolysis (5O mM effect of activated complement (AC) upon H,SO4) followed by Smith degradation hepatocyte viability as assessed by cellular (sequential sodium periodaite (75 mM), ATP levels and Oxygen free radicals do not activate the gluconeogenesis. Isolated zymogens of human pancreatic proteases sodium borohydride (0( 1 M) and sulphuric rat hepatocytes prepared by the method of acid (25 mM)). Peroxidase tagged lectins Krebs (1974) were incubated in Krebs- were used to analyse terminal P M GUYAN, J BUll ER, AND J M BRAGAN/A (Tlie carbohy- Henseleit bicarbonate buffered medium, drates aftcr eaich step. Mild acid hydrolysis pH 7-4, 37°C±fresh sera with complement Medical School, University of Manchester, Oxford Road, Manchester) The current consistently eliminates LFA and UEA I activated via the classical pathway (by pre- interest in superoxide (04 and hydroxyl binding. Smith degradltion then causes loss incubating with anti-albumin antibody, of PNA binding with retention of WGA+. 30 (OH) free radicals as the initiating mecha- 37°C, min). ATP levels were significantly nism in pancreatitis, led us to investigate The pancreatic cancer marker epitope reduced in the hepatocytes exposed to AC their effect on pancreatic therefore comprises: compared with controls (not exposed to proteases, zymogens and trypsin inhibitor. Equal con- galactose Ii 1-3 NAc galaictosiamine-R. sera) after 20 mins incubation (from centrations of these free radical 11-8±0-79 nmol ATP/mg hepatocyte pro- species were generated, in different doses, using a tein, mean±SEM, n=5 to 7-5±09-, fucose sialic acid n=5, caesium source (0.5-13 kraids) and a linear p<0'0I) and after 4() mins (6-8±0-77, n=5). Persistence of WGA+ on epitope negative without activation of accelerator (3-15 krads). Using specific Sera prior complement substrates and sensitive fluorometric assays chains after Smith degradation implies that caused no significant reduction in ATP expression of the marker results from it was confirmed that trypsinogen, chymo- http://gut.bmj.com/ (I 1-5±10-(, n=5 at 20 mins, 11-8+±0-79 at 40 trypsinogen and proelastase in human pan- incomplete glycosylation. mins). Gluconeogenesis was reduced in the creatic juice were not activated upon hepatocytes exposed to AC (2'08±t)05 nmol irradiation, whilst trypsin inhibitor was glucose/mg protein/min, n=4) compared also with controls (4-7±0-33, n=4, p<0(0l). unaffected. A dose dependent (() 5-2 Difluoromethyl-ornithine (DFMO) inhibits krads) loss of trypsin was observed Activated complement is cytotoxic to activity adaptive ileal mucosal hyperplasia after isolated in dilute aqueous solutions of the pure pancreaticobiliary diversion (PBD) in the rat hepatocytes and could therefore be enzyme, but not in activated human pan- an important cause of hepatotoxicity in creatic juice (doses 0(5-15 krads). whereas vivo. T BAMBA, S VAJA, G M MURPHY, AND R Ii on September 26, 2021 by guest. Protected copyright. in the juice there was a dose dependent loss [)OWL IN(. (Gastroeniterologyv Uniit, Guy's of chymotrypsin activity. Campus, UMDS of Guy's atid St Thomas' These in vitro studies indicate that if O,. Hospitals, Lonidoni) Pancreaticobiliary Is sympathetic activity really increased in and/or OH are involved at the initiation diversion, achieved by transposing 5() cm of cirrhosis with ascites? stage of pancreatitis, they exert their jejunum to lie between pylorus and damage by mechanisms that do not involve ampulla, stimulates ileal mucosal hyper- A J MACGILCHRIST, L G HiOWES, C HAWKSBY, J activation of pancreatic protease pre- plasia but the role of polyamines and related REID, AND T J 1IIOMSON (University Depart- cursors. This resistance to oxidative stress enzymes (ornithine decarboxylase: ODC ment of Materia Medica, Stobhill Hospital, could be due to the presence, in pancreatic and diamine oxidase: DAO) in this adaptive Glasgow) The increased plasma nore- juice, of a recently described novel enzyme reponse, is uncertain. Since ODC is inhib- adrenaline (NA) recently reported in severe that scavenges hydrogen peroxide. ited by DFMO, we studied the effects of 2% cirrhosis may be due to increased spillover DFMO in drinking water on indices of into plasma from sympathetic nerves (and mucosal mass, ODC, DAO, and alk phos by implication, increased sympathetic Carbohydrate sequencing of a new pan- activities and polyamine levels in six groups activity), or to reduced clearance of NA due creatic cancer glycoprotein marker of rats studied two weeks after surgery: (i) to reduced hepatic metabolism. We have transected controls (TRC), (ii) TRC+ developed a new method to calculate NA C K CIIING AND JONATIIAN M RHODIS DFMO (starting three days pre-op), (iii) spillover and clearance by intravenous (University Dept of Medicine and Walton TRC pair-fed with group (ii), (iv) PBD, (v) infusions of sub-pressor doses of tritiated Hospital, Liverpool) We have recently PBD+DFMO and (vi) PBD pair-fed. NA. We studied 14 cirrhotics with ascites identified a 3-5x 10)6 D serum glycoprotein Ornithine decarboxylase activity (nmol and 13 age-matched patient controls. All that is highly specific for pancreatic canccr h 10cm ')increased from 2'60+SEM 0-47 subjects studied were in-patients, off and distinct from previously described (TRC) TO 6X87±2-38 (PBD; p<0)-()5) but Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A13(95 DFMO markedly inhibited ODC to remained stable for at least 10 minutes. The Restitution of colonic mucosa in vitro 0-45±00-5 (TRC; p<0(-(0) and 0(75+±021 electrode showed a curvilinear current v (PBD; p<0(002): pair-feeding had no sig [BA] relationship (at I mM, 0(61±SEM P H ROWE., N 1 K FA(i(G, ANI) R C MASON effect. There were corresponding changes 0-04 ptA/mM, n=6). Over 30 hours there (Departments olf SurgerY and{ Pathology., in putrescine and spermidine but not in was a fall off in electrode response (at UMDS, Gi s's Hospital, Londtloni) It has spermine. Alk phos activity increased 4-6 1 mM, 0(34±00-3 [tA/mM) attributable to previously been reported that complete fold after PBD but was unaffected by decreased enzyme activity. The electrode restitution of epithelial integrity in DFMO or pair-feeding. Conversely, DAO was then compared with the standard amphibian gastric mucosai occurs in vitro activity fell after PBD in both ad-lib and spectrophotometric assay in determining within four to six hours after injury by IM pair-fed groups but did not change with the total [BA] in methanolic extracts of 10 NaCI. The process of restitution has not DFMO. Difluoromethyl-ornithine inhib- gastric aspirates, good agreement being been previously described or investigaited in ited PBD-induced increases in mucosal wet obtained (r=-)99, p<0-001). With further the colon. Using chambered bulIlrog wt, prot and DNA/10cm by34%, 31%, and development, including miniaturisation and colonic mucosae (n= 10) exposed to IM 47% respectively (p<0(05-0(0 1). computerised correction for enzyme decay, NaCI in the luminal chamber exhibited ain The results confirm that ODC and poly- this electrode should prove suitable for in immediate fall in potential diff'erence (PD) amines play a vital role in the cellular vivo monitoring of intragastric BA activity from baseline values of' -58-6±6-3 mV control of intestinal adaptive growth. and DGR. (±SEM) to 0 mV (p<0)-05) and a fall in resistaince (R) from 216± 18-3 Q cm' to 8±4-8 Q cm' (p<0-05). Tissues removed (n=-5) following NaCI exposure exhibited An integrated study of gall bladder (BG) severe surface mucosal injury with denudai- Is continuous ambulatory monitoring of motor function in gall stone patients tion of the basal lamina. After 10 minute duodenogastric reflux feasible? In vitro NaCI exposure, and replacement of NaCI assessment of an enzymatic amperometric P PORIINCASA, P MITRA, M MA(ihISOULD[OO, G M with Ringer's solution, at luminal pH 5() bile acid electrode MURPIIY, AND R 11 DOWILING (Depts of when tissues (n=5) were allowed to recover Medicine and Pathology, Gucy's Camnpus, for four hours in the chambers, there was D ARMSTRONG, B LENNOX, J ALBERY, G M UMDS of Guy's and St Thomas Hospitals, histological reconstitution of the surfatce MURPHY, AND R H DOWLING (Gastroenter- London) Gall bladder emptying in response epithelium and the PD and R had returned ology Unit, Guy's Campus, UMDS and to exogenous or meal stimulated CCK is to -43±4'5 mV and 220±14 2 Q cm' Dept Physical Chemistry, Imperial College, impaired in gall stone patients but few respectively, not significantly different from London) Duodenogastric reflux (DGR) has studies have related cholecystokinetics to the PD and R observed in control tissues been implicated in the pathogenesis of quantitative histology of muscle mass or the maintained for four hours in the chambers. gastric mucosal damage. Current DGR degree of inflammation in the GB wall. Control tissues (n=4) showed no significant http://gut.bmj.com/ quantitation techniques provide only inter- Therefore in longitudinal strips of fresh change in PD or R and no histological mittent or short term monitoring of an GB's, we studied tensiometric contractile evidence of damage. episodic phenomenon. Our aim is con- responses to CCK-OP (0-875x 10"' to 10 We conclude restitution of the amphibian tinuous 24 h ambulatory monitoring of M) and acetyl choline (ACH: 5x 10 'to 10( colonic mucosa occurs in vitro following DGR, using intragastric total BA concen- M), recording the max tension produced, injury by IM NaCI. trations ([BA]) as a marker of DGR - and relating the dose required to generate analogous to pH monitoring in the investi- 50% max response (Ds,) to muscle area gation of reflux of total cross sectional area) and an oesophagitis. Any [BA] (MA'/O on September 26, 2021 by guest. Protected copyright. monitoring technique must be sensitive, inflammatory score (6 parameters). Effects of starvation and refeeding on specific, stable and able to detect all intra- In 14 patients with moderate chronic electrogenic ion transport in the rat colon: a gastric BA. We therefore used the estab- cholecystitis there was myohypertrophy, model for famine diarrhoea? lished enzyme reaction as the basis for a BA the MA% of 15-0±SEM 1-43 being greater electrode. A platinum disc, coated with a (p<0.001) than that in four histologically 11EL [N NZEGWU, A YOUNG, AND R J l.-VIN conducting organic salt (NMP+-TCNQ ), is normal GB's (7-72+0-24). The MA%0 (Department of Physiology, University of covered by a membrane enclosing the 3-ca correlated (r=0-62; p<0-005) with the CCK Sheffield, Western Rank, Sheffield) The OH steroid dehydrogenase. 3-ct BAs are Di,, which was also greater inWinflamed aetiology of the diarrhoea induced by oxidised by the enzyme, producing NADH (3-45±0+006) than in normal (0-54±0 1t) famine and by subsequent refeeding of which is then oxidised by the NMP' - nM) GB's but less ACH was required for victims is unknown. In the rat model, star- TCNQ , returning NAD' as substrate for the DR (6-38+1-3 v 15-0±9-9 FM) - vation hypersensitises the small intestine to the enzyme. Oxidation of NADH generates perhaps because of denervation hyper- secretagogues resulting in greater fluid and a current proportional to [NADH], and sensitivity. The max tension (kg/cm2 electrolyte secretion, but little is known thus to total [BA] in solution. The semi- muscle) in response to CCK was compar- concerning the colon. Male rats were pro- permeable dialysis membrane controls BA able in normal (0-29±0.05) and inflamed gressively starved for up to 72 h and then entry and prevents enzyme loss. We des- (0-31+0-05) GB's but after ACH, it Was refed for up to a further 72 h. Electrogenic cribe the in vitro assessment of this elec- greater in normal (0-35±0-15) than in ion transport was measured as the short trode using solutions of chenodeoxycholic cholecystitis (0- 19±0-02). circuit current (Isc) under basal conditions acid, deoxycholic acid and their glycine and These results confirm our in vivo findings and with bethanecol (I mM) stimulation. taurine conjugates (0-1-2-0 mM). Maxi- and suggest that despite myohypertrophy, Basal Isc fell during starvation, a maxi- mum plateau current was generated with the inflamed GB is less responsive to CCK, mum decrease of 18% (p<0-05) occurring each [BA] within three minutes and but more sensitive to ACH, than normal. after 72 h (n-=29) compared to fed controls Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1 396 The British Society of Gastroemterology (n=26). It then increased over the 72 h J N PRIMROSEI, D Jo(HNSI)ON, C SHAW, AND) K I) of indomethacin (1-0 mg/ko iv), were refeeding period until it exceeded the fed BUCHANAN (University Departtnent of macasured in 15-min periods for 2x60 nimi levels by 18% (p<0-05, n= 12). Bethanecol Surgery, Leeds General InfirmnarY antd following a 60) imilt conltr-ol period. 5-HI stimulated A Isc (A Isc=Max Isc- Basal Department Metabolic Medicine, Queen.s rcvcrsed fluid absorption (+ 3.9()-7 Inl/h/ Isc) increased significantly after 48 h of University, BelJast) The aim of this study cm; mrcan±SE) into protusC sccrction starvation (+40%, p<0(0l, n=10) and was to determine the effect of SMS on the (-1 7+±()5; p<0(0(l Duncan's multipic remained at this raised level. On refeeding dumping syndrome (DS) provoked by riange test) and significantly increaised JFR it returned to the fed level only after 72 h hypertonic glucose, and on the accompany- of PGE. (0 11 +01)(3 v () 40+() 1) ng/min; (+ 12%, n= 12, p>0'05). These results may ing changes in PCV, BG, and GI peptides p<0(-0 ). Indomethacin piartly restored partially explain the famine diarrhoea and (insulin, N-terminal-glycogen-like immuno- fluid aibsorption ( + 1 2+05 p<0-(0) and the diarrhoea associated with realimenta- reactivity (N-GLI), GIP, VIP, neurotensin inhibited JFR of PGE. (0)21 ±10))4 tion in man. Support from the British and N terminal neurotensin immunoreact- p<0()05). Thcse rcsults providc furthcr Digestive Foundation is acknowledged. ivity (N-neuro)). evidenicc in support of the thcory that PGs Dumping was provoked in 10) patients are involved in intestinal fluid sccrction with DS by means ot 350) ml 25%/ glucose. induced by 5-HT. Atrial natriuretic peptide influences electro- Patients received pliacebo, SMS 50) ug or lyte transport in the large intestine SMS 100 ug, given in random order on separate days. Blood samples were taken Human upper gastrointestinal transit and K J MORIARTY, N B HIGGS, M LEES, A IONGi, G for PCV, BG, and GI peptide estimations carbohydrate absorption are modulated by WARHURST, AND 1 A IURNBERG (Department throughout the two hours of the test. beta-adrenoreceptors oJ Medicine, Hope Hospital (University of With placebo, all patients experienced Manchester School oj Medicine), Salford) severe symptoms: nine had early dumping A S MCINIYRIE, 1) (i III)OMPS()N, W R BURNHIAM, Atrial natriuretic peptide (ANP) possesses and thrce, late dumping. Symptoms were ANI) F1 WAI.KE.R (Dept Gastroenterology, 7'The potent diuretic and natriuretic properties abolished or much reduced aftcr either dose Lontdoti Hospital (VWhitechapel), London and appears to play a central role in fluid of SMS. antI Oldchurch Hospital, Rotn/ord.FrdEssex) and electrolyte homeostasis by an action on Somatostatin analogue is effective in (Control studies: O)rocaecal transit ol'a soup the kidney. We examined the influence of treating the symptoms and reversing the laictulose metal was measured in 26 subjects ANP on the large intestine, because this chainges in PCV and BG of' dumping pro- by the serial hreaith hydrogen method. organ is also intimately involved in homeo- voked by hypertonic glucose. The incre- Ciarbohydrate athsorption was estimnated stasis. Segments of distal colon of male ments in GI peptides are reduced signific- with at series of fructose meals, fructose Sprague-Dawley rats were stripped of antly by SMS, but only the change in N-GLI being varied in 10) g increments (2(0-(90 g); muscle layers and mounted in flux cham- correlates with the change in PCV (RS= the smallest dose producing ai hydrogen rise bers. Atrial natriuretic peptide, when 0(82, p<0'05). N-GLI may reflect, or be indicated that the absorptive theshold wias http://gut.bmj.com/ added to the serosal aspect of the mucosa, in associated with, the changes of dumping. just exceeded. Transit wals consistent concentrations ranging from 10 t-1() ' M, within, but varied widely between indi- caused a rapid, dose-dependent rise in viduals (median 55. range 32-172 min). short-circuit current (Ij,) and transmucosal Fructose aibsorptive threshold showed electrical potential difference (PD). Atrial Prostaglandin (PG) E, is a mediator of 5- similar interindividuali variation (mediain natriuretic peptide (11) M) elicited a peak hydroxytryptamine (5-HT) induced fluid 40) range 30)-8ff g and correlated with increment in I, of 59-2±6-7 ,uA/cm' (n=8, secretion in the human jejunum trIansit (T-().70, p<0-0() 1 p<0()(l) and in PD of 2-97+±)3 mV (n=8, B-adrenergic stimulation: Isoprenaline on September 26, 2021 by guest. Protected copyright. p<0(00l). A rise in I,. and PD is generally 1. K MUNCK, A MlERT/-NIIF SIS.N, Ii WlSI I, K (Bl alnd B2) consistently inhibited transit associated with enhanced secretion. The BUKIIAVIE, 1. BI UBILIER, ANI) J RASK-MAI)SIFN (mean A 30-4+3-7 mnins, p<0(-00l) aind response to ANP (It) M) was, however, (Depts of Medic al Castiroenlerologv, increased fructose absorption (mean A 15 virtually abolished by pre-treatment with Bispebjer,g, atnd Herlev Hospials, Univ of g), the magnitudc ol response varying the calcium channel blocking drug, d,l- Copenhalgen, Dentmlark anzd Ep C('liii inversely with control data (T=-) 52. verapamil (It) M mucosally and serosally), Pharmaccol Univ ( CGraz, A lstriai) Studies p<0(0 I ). Atenolol (B I antagoniist) and also by using a calcium-free (no in the rat jejunum in vivO have shown that abolished the cttfct. calcium +2x 1)0 ' M EGTA) solution on the 5-HT causes fluid secretion accompanied by B-adrenergic blockade: B-blockade (B serosal surface. luminal PGE, releatse. These effects cain he and B2 or B I ailone) aiccelerated transit These findings support a role for ANP in blocked by indoomcthacin aind kctalnscrin, (mean A 21 7+7 4 mins, p<(0)2) aind the regulation of colonic ion transport and suggesting that PGE, may he ain important reduced tructose absorption (meiian A 15 g); suggest that ANP may elicit secretion via a intermediate in the transduction mecha- the effect wias directly reliated to control calcium mediated mechanism. nism leading to 5-HT induccd secretion. To trainsit (T=0()49, p<0(02). test this hypothesis in man 'stcady state' Thus a tonically active B -Iadrenorecep- perfusions (9 ml/tnin) of 31) cm proximal tor palthway moduliates normal nutrient jejunum were performed in eight healthy triansit iIIad carbohydrate aibsorption alndi SMALL INTESTINE volunteers, using a triple-lumilen tube and a aiccounits for up to 67(YO of differencc Ringer's solution with ''Cr-EDTA as a between individuials. Somatostatin analogue SMS 201-995 in the non-absorbable mnarker. 'Ihe eftects of dumping syndrome: effect on packed cell exogenous 5-HT (10) ftg/kg/min iv) on fluid volume (PCV)? Blood glucose (BG) and transport and jejunal flow rate (JFR) of Characterisation of defective sodium plasma GI peptides PGE., before and after the aidministraition coupled glucose transport in congenital Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 1 397 glucose-galactose malabsorption (GGM), greater than controls (14±2 v 5±0-9 [imol/ Application of organ culture to the investiga- using jejunal brush border membrane day, x± SE, p<0-005). Antibiotic tion of lectin-induced damage to the brush vesicles treatment reduced SFBL DMA from border membrane 13-1±2-2 to 3-8±0+6 [tmol/day. p<0(02. To I W BOOTI1, D SULE, P B PATEI, G A BROWN, confirm the pathway from PC to AA, R M BA1, C'A HART. 1 MC(IiAN,13 GFiT.l AND AND K BEYREISS (Institute of Child Health, orogastric intubation was performed with J R SAUN DF RS (Der)(trllnent.s of VeterinarY University of Birmingham and Karl Marx (N-methyl-'H) PC and -H-DMA identified Patholog,', Medical Microbiology (1a1nd University of Leipzig, Germany) To date, in the urine. Microbiolog,y, Universitv of Liverpool) the defect in D-glucose transport seen in Humani study: 10 controls and 12 SIBO Ingestion of lectins such as phytohaiemalg- GGM has not been directly shown in the patients (jejunal culture>l05' orgs/ml) were glutinin in red kidney beains is an importaint jejunal brush border membrane. We have given a fatty meal to stimulate biliary PC. cause of food poisoning, but the patho- therefore prepared brush border membrane Urine 4-hr AA excretion was measured and physiologicill mechanisms ire poorly under- vesicles from jejunal biopsies from a three results expressed as total AA (DMA+ stood. Lectins bind to specific carbohy- year old with GGM, and from nine control TMA)/creatinine ratios. The excretion ratio drates in brush border glycoproteins, but children, using a miniaturised differential was greater in SIBO patients, 98±22 v 33±3 the relationship between binding and lectin- centrifugation technique. Diagnosis in the (controls), p<0-02. This study indicates toxicity is unclear. In this study, the ultria- patient was confirmed by jejunal steady- greater PC degradation in both the animal structural effects of lectins on the brush state perfusion studies, which showed model and SIBO patients. Antibiotic treat- border have been exaimined during orgain defective glucose and galactose absorption ment reversed this effect in the animal culture and related to their receptor (p<0-((l), but normal fructose transport. model. The bacterial degradation of PC specificities. In brush border membrane vesicles from may be a factor in the pathogenesis of the Explants from ratbbit ileum were cultured controls, an inward Na+ gradient (100 steatorrhea in SIBO. for 24 hours in medium containing cach of mmol/l) enhanced 15 sec D-glucose uptake 10 lectins, and were then processed for x6-5 (p A1398 The British Society ofGastroemiterology eight suppositories over four days- that is, Concomitant presence of IgE plasma cells activity, flow rates (by "4C-PEG) and intra- 12 hourly, containing either 100 mg diclo- in duodenal and bronchial mucosae in luminal bile acid concentrations (BA) were fenac or inert substance. Abdominal pain asthmatic patients measured in a 40 cm jejunal segment was recorded by the patients regularly on a proximal (n=6) and a 40 cm ileal segment 10 cm visual analogue scale (VAS) after C ANDRf, [) GINDRE, Y PACHIECO,.I)1DSCOS, distal (n=6) to an ileal port infusing an operation, both 'at rest' and after coughing. ANt) M PERRIN-FAYOLILE (Laboratoire isotonic clectrolyte solution with or without Patients were closely monitored for any d'Inmunopathologie Digestive INSERM, GCDC for 80 min. During GCDC infusion unwanted symptoms or complications, and Ceentre Hospitalier Lvoon-Suld, Pierre- (6(0 [tmol/min) jejunal and ileal transit were all drugs administered were recorded. Benite, France) Immunoglobulin- markedly (p<0-05) delayed (31.6+7.7, Thirty one diclofenac and 26 placebo containing cells of all classes were counted mean±SEM. v 14 5±3-8 min and 37-)0±5.7 patients fully completed the study. Daily according to the tissue unit method in v 21-0+3-5 min, respectively), while flow pain scores measured 'at rest' were similar duodenal and bronchial mucosae in control rates did not change significantly (4-6±0-6 v between groups. On coughing diclofenac subjects and asthmatic patients. 4 5+±06 ml/min and 4X8±0 5 v 4 2±0-3 patients experienced consistently and In control subjects (n=6) the mean per- ml/min, respectively). Per cent duration significantly (p<0c02) less pain on all the centages of IgA, IgM, IgG, IgD, and IgE pressure activity in the ileum decreased post op days. Opiate analgesic consumption cells were 74, 8, 17, 1, and (O respectively in (p<0.05) promptly (60)±8 sec) after the was similarly reduced in the diclofenac the bronchial mucosa. In 25 control subjects start of GCDC infusion (6.9% + 1-6 v group. There were no differences in post- the mean percentages of IgA, IgM, IgG, 17 9'Y.±4-2). Inhibition of jejunal motility operative complications between the group. IgD, and IgE cells were 75, 13, 10, 1, and 1 was more gradual and reached significance It is concluded that diclofenac is of use in respectively in the duodenal mucosa. The (p<0(05) only 30 min after start of GCDC post abdominal surgery pain relief when same studies were performed in 15 infusion (18X9(X.±3-2 lo 35-2%±7-1). Intra- given 12 hourly as a 100 mg suppository. asthmatic patients. The differential counts jejunal BA were not altered by GCDC of IgA, IgM, IgG, and IgD cells did not infusion, while intraileal BA increased differ from the values observed in controls. (p<0.05) during GCDC infusion and A significant increase of IgE cells was found showed a 35-92% (median 45%) absorption SMAILL INTESTINE in the duodenal and bronchial mucosac of GCDC by the 40 cm ileal segment. from nine patients, the average values being In conclusion these observations suggest Use of endoscopic biopsies to diagnose 13'% in the digestive mucosace and 24%S in the existence of a regulatory mechanism in disaccharidase deficiencies the respiratory mucosa. No IgE plasma cells healthy man, whereby presence of GCDC were observed in the mucosae from five in the ileum inhibits motility and delays J A SMITH, J AMOAH, D O REILLY, J F MAYBERRY, other patients. In the last patient there were transit throughout the smaill intestine. AND R G LONG (Medical Research Centre, no IgE cells in the intestinal mucosa but Citv Hospital, Nottingham) Endoscopic these cells accounted for 18% in the http://gut.bmj.com/ duodenal biopsies can replace Crosby respiratory mucosa. capsule jejunal biopsies for the histological The similarities of the local allergic diagnosis of malabsorption despite the response in asthmatic patients may be inter- Wheat protein, gut abnormalities and presence of shorter villi and Brunner's preted in three ways. Food allergy may be rheumatoid arthritis glands. As endoscopic biopsy is quicker and involved in many asthmatic patients. The easier to perform, we compared disacchari- immune response could be the consequence CLIONA ) FARRIEILY, I) MAR'I'EN, I) MELCIIER, R dase levels in endoscopic biopsies from the of an allergic stimulation at both levels. The SF11ERWOOD, A J GOILDSTHIN. FERNANDES second part of the duodenum and Crosby observed data also correspond to the con- ANI) B MACDOUGALI. (Schlool of Biological on September 26, 2021 by guest. Protected copyright. capsule biopsies from the proximal cept of an universal mucosal immune Scienices, University of Su.ssex anid Depts oJ jejunum. Thirty patients had normal histo- system: cells stimulated at one mucosal site Histopathology, BiochemistrY, Rheluma- logy and 12 patients had partial or total may migrate to other mucosal sites. tology, anid Gastroeniterology, Royal Suissex villous atrophy. Two normal patients had CountY Hospital, Brighton, Suissex) There is primary hypolactasia diagnosed by both increcasing interest in the role of the GI tract biopsy techniques. Mean+SEM lactase in the pathogenesis of rheumatoid arthritis levels in 28 normal duodenal biopsies were Feedback regulation of transit and motility (RA). We studied this role in 87 RA 12 1±2-3 U/g protein, and in jejunal biop- in the human jejunum and ileum by ileal patients (65 women; mean age 62). Using sies were 21-2±4-0 U/g protein (p<0-()1). A infusion of glycochenodeoxycholic acid ELISA, 50 of the 87 had raised levels of IgG parallel statistically significant reduction in (GCDC) to wheat and/or milk protein (41 were the duodenum was seen for maltase and positive for wheat, six for milk and 12 for sucrase results. In villous atrophy secondary R PENAGINI, R C SPILLER, JJ MISIEWICZ, AND both). Ninety per cent of the antibody disaccharidase deficiencies were found and P G FROS'I (Depts of Gastroenterology anid positive group had raised levels of IgA corresponding lactase results were 200+06 Nutrition, and of Chemical Pathology, rheumatoid factor (RF) compared with only and 4-0+1-2 U/g protein. Thus normal Central Middlesex Hospital, London) The 27°/ (p<0-00l) of antibody negative jejunal levels are consistently higher than present study examined the possibility that patients (both groups were on similar treat- duodenal levels but results in villous presence of GCDC in the human ileum in ment regimens). atrophy are not statistically different. We amounts comparable to a bile acid pool (5 Jejunal biopsies were ciarried out on 25 of conclude that duodenal biopsies are a valid mmol) inhibits fed ileal and jejunal motility. these patients: 15 had raised levels of both alternative to Crosby capsule jejunal biop- T'en healthy subjects were studied. IgA RF and wheat protein IgG (AB+); the sies for the diagnosis of both primary and Transit times (by a marker bolus of bromo- remaining 10 had normal levels of both secondary disaccharidase deficiencies. sulphthalein), intraluminal pressure antibodies (AB- ). The biopsies were Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 1 399t assessed using standard histological, stcreo- Is long term home parenteral nutrition centerocytes for cach biopSy. JeCju.nal hiop- logical and biochemicail techniques. Villous worthwhile? sies f'rom aige matched maile control sublhjets aItrophy was present in six of the AB + but in (n=seven) were similalrly treated. No only one of the AB- patients. This wIs M A STiKES, J 1 SiiAF1IFR. M 11 IRVIN(, (ON mucosal eniteropathogens were detected in confirmed by ai lower villous surface/volumc BEiiAI O')F i111. UKII I(MIi PARiNiALRAI ainly bliopsy. Enterocytes appeared normal ratio (77-8 17-3 SD) in AB+ patients when N RI lI ION (ROUP) (Departmnent.s of and villous aitrophy (VA) with crypt hyper- compared with AB- (97-9±21 8: p<0)-02) Medicinea(1d(1 Surgersy, University ol Ma,l- plaisia wats the only abnormality detected at or 10 age-matched control piatients (125+ chester School oJ Medlicinie, Hope Hospital, all staiges of FIIV disease; S:V (control) 17.9; p<).-00 1). Lactase levels ( meaisured as SalJord) There are 241 patients entercd on 49-2+6-2, (HIV) 38-4+94, p=)-006; Cl umol/min/g tissue) were ailso lower in the the HPN register for the United Kingdom (control) 32-5±6-8 (HIV) 38X8±75, AB+ group (34±2 () SD) than in the AB- and Irel.ind. Fifty two of these haive beenl on p=0)-)498. Crypt lcngth also invcrscly (5-7±2-5; p have becn on HPN for a total of 19t) years. Forty one of themnare still on HPN, the Familial visceral myopathy longest has been on tor seven years. Four paticents have resumcd enteral fceding, the I'ANC RI.AS ( A RODRIGUES, N A SiiiHPiIERt), I' R IlAWITi Y, J longest 41 months after commeclcing. Six of 1 I ENNARD-JON1-S, ANI) If H iIIOMPSON (St these patients have died, two after five years Glycochenodeoxycholic (GCDC) and Mark's Hospital, Cit'v Rotid, LoIndoo, The on HPN. glycocholic (GC) acids infused in the human Londotn Hospital (Whitechapel), London) These longterm patients have a signific- jejunum inhibit small bowel motility and The first British kindred with autosomail antly better lifestyle (p<()-()l ). with a lower transit dominant viscerail myopathy is described: incidence of sepsis (0-25 per patient pcr Six in two all affected members generations year; p<0)-05), and a lower incidcnce of R PENAGINI, J J MISIiWICZ, ANI) (iG FROST had intestinal pseudo-obstructioni which total complications (0(56 per patient per (D)epts of Gastroenterolog' anid N1utritiont, was demonstrated by conitraist radiology. and of Chemical Central Middle- year; p<0))(0l), than for the group of HPN Pathology, http://gut.bmj.com/ Five of these patients had ai megaiduo- sex patients as a whole. Hospital, Lonldoni) The present study denum, two haid diminished oesophageal Home parenteral nutrition is a highly examined the effect of jejunatl infiusion of peristalsis, four small bowel aind four succcssful treatmcnt in the managemcnt of GCDC and GC on small bowel transit time colonic involvement. One patient had patients with longterm intestinal failure. (SBIT: lactulose 5 g-hydrogen breath test), dilatation of one ureter and incomplete fasting jejunal motility aind serumtbile aicid blaidder emptying on intravenous concentrattions in 18 healthy subjects. urography. Each subject was studied during jcjunal The clinical onset of the disease occurred Jejunal mucosal architecture in HIV infusion of saline ailone (control) aind during in childhood or aidolescence with dysphagia infected male homosexuals infusion of at least one of four saline solu- on September 26, 2021 by guest. Protected copyright. (n=-2), abdominal pain (n=5). abdominal tions containing: (1) GCDC 3-3 mmol distension (n=6). constipation (n 4), P A BAIMAN, A MtLL ER, S FORSTE1R, A PINCH- (n=5), (2) GCDC 3.3 mmol+lecithin 08- diarrhoea (n=4), aind urinary symptoms ING, W tIARRIS, AND (G F GRIFFIN (Departments mmol (L) (n=5), (3) GCDC 5 rnmol+L (n=2). The two most severely affected of ('omnunicable Diseases tand Histo- (n=6), (4) GC 5 mmol+L (n=6). Eaich individuals arc on home parenterill nutri- p)athologs', St George's Hospital atnd St solution was infused in X() min on a separate tion and have undergone surgery for the Mars 's Hospital Medical Schools, LonIdon) day in raindomised order. Fasting jejunal alleviation of symptoms. Three other Crosby capsule jejunal biopsies from HIV motility was recorded in the experiments patients have mild, non-progressive antibody positivc male homosexuals (n= 20: testing (3) and (4) only. Blood samples were symtoms. and have been able to maintain asymptomatic=five, persistent generalised collected at t), 30, 60, 9t), 120, 15t) min from normal nutritionail status without special lymphadenopathy =nine, AIDS=6) were start of infusion for measurcment of tottil measures. The sixth family member has subjected to light microscopy and stained bile aicids (cnzymatic method): integrated been lost to follow up, and his current status with H and E, modified Zichl-Neelsen, incremental response (BA IIR) was is unknown. Giemas, PAS and Gram (to detect mucosal calculated. The main pathological features consisted enteropathogens). Mucosal surface area/ Results (mean+SEM) show that GCDC of marked dilatation alnd thinning of the volume ratio (S:V) was dctermined using 5 mmol+L and GC 5 mmol+L delayed bowel wall, and vacuolar degeneration of Wcibel graticule. Crypt length (CL) was (p<0-05) SBTT when compared with con- the longitudinal layer of the muscularis assessed by counting enterocytes from crypt trol infusion (158X3± 12S5 min v 111-7+17-6 propria with fibrosis and elastosis. The base to crypt/villus junction. Intraepithelial min aind 103-3±21-8 min v 7()()+ 14.9 min), submucosal and myenteric nerve plexuses lymphocytes (IEL), detected using inhibited (p<0-05) the percentagc duration appeared normal and there was no histo- immunoperoxidase technique (leucocyte pressure activity of phasc 2 (131± 1-s'8 logical abnormality ot the blood vcssels. common aintigen), were counted/500 28X1 +3.4%Y0 and 2932±55.5(Y v 34-9±3-9%), Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 14(00 The British Society ofGastroenterology but did not change duration of migrating cholangiocarcinoma after intubation by the ing endocrine tissuc. The appearances are motor complex, or of its phases. Glyco- percutaneous route and intralluminal radio- suggestive of pancreatic endocrine neo- chenodeoxycholic 3-3 mmol+L had a less therapy. We report a less invasive endo- genesis and regeneration. When combined consistent effect on SB1T (p=NS). All four scopic technique in which the Iridium-192 with a surgical procedure to divert portal infusions containing bile aicids increased wire source is inserted down a nasobiliary blood across the pancreas longterm, the (p<0-05) BA lIRs in comparison with catheter placed within a previously inserted pancreatic changes associated with control infusion. endoscopic biliary prosthesis. Six men, implanted hepatocytes are even more In conclusion these observations suggest mean age 64 years (range 41 -80) with marked. a role of endogenous bile acids in the inoperable cholangiocarcinoma hiave so far The disposition of proliferating liver cells reguliation of small bowel motility and been treated. Following biliary decompres- as an outer mantle around islets was sug- transit. sion when the serum bilirubin had fallen gested to be supportive evidence for the substantially radiotherapy was commenced. existence of pancreatic hepatotrophins. The The Iridium wire was loaded into a 0))038" regenerative pancreatic changes that have The histopathology and staging of Teflon-coated movabie core guide wire and been demonstrated raise the possibility of carcinoma of the ampulla of Vater inserted through the nasobiliary catheter an hepatic pancreaticotrophin. under fluoroscopic control. A total dose of I C IAILBOTI, J P NE'OPiOlFtMOS, I) (CARR-I(CKi., 60(X) rads was aidministered over a meian of four days (range 3 3-48). During this ANI) I) SIIAW (Dept oj Patilologv anid Faecal chymotrypsin accurately predicts Surgery, Clinical Science.s Blildling, period serum bilirubin increased slightly in three patients but fell again aifter removal of exocrine pancreatic function in infants and Leicester RoYal Infirmntarvy, Leicester) children Carcinomas of the armpulla are uncommon the Iridium wire. Mean hospital stay after and data concerning their paithology and this treatment was 6-3 days (range 1-26). The only complication was mild cholangitis G A BROWN. D SULE. J W PUNrIS, ANt) I W behaviour aIre inconsistent aind of question- BOOi iT (Institute of Child Health, University able reliability. We have analysed the in two patients. Two patients have since required stent replacemcnt. One patient of Birmingham, Birmingham) Faecal tumour type, grade, paittcrn of local inva- chymotrypsin measurements have been sion and outcome in 26 carcinomas surgic- has died 105 days after treatment: the remaining five are all alive bctween 10( and proposed as an alternative to intraduodenal ally resected over a 13 year period. Twenty- tests of pancreatic function but with five (96%/O) wete intestinal type adcno- 430 days. This technique was well tolerated by all patients and in view of the reduced insufficiently rigorous validation. We have carcinomais, the degree of differentiiation reassessed the test by simultaneous being good (eight), moderaite (13), or poor morbidity of endoscopic compared with transhepatic prosthesis insertion should be measurements of faecal and duodenal (four). Adenomca cocxisted with aideno- chymotrypsin in 30 children aged three carcinoma in 1 1 cases, six ol these being well considered in patients with inoperable cholangiocarcinoma. weeks to 13 years with exocrine pancreatic http://gut.bmj.com/ differentiated (low gradc). There was function ranging from nil (five), through epithelial dysplalsia of duct epithelium partial insufficiency (one), to the physio- adjacent to 10 carcinomais, only two of these logical range (24). Mean faecal chymo- being low grade. Morphological changes in the pancreas, trypsin concentration was determined, for Forty five per cent of paitients survived suggestive of endocrine regeneration, each child, from three random stools live years. The fivc yeair survival raite for the induced by transplantation of isolated collected on separate days within 72 hours whole series (estimated by the Kaplan- hepatocytes of a conventional pancreozymin stimulation Meier mcthod) was 520o and, with low test. In the 25 children with measurable on September 26, 2021 by guest. Protected copyright. grade 83% adenocarcinomai, (p The British Society of Gastroenterology A 14()1 Cytological diagnosis of hepatobiliary and was expressed in arbitrary units by compari- Aspirin and bleeding peptic ulcer pancreatic malignancy son with a standard curve of' a knowni P J PRI( IiARi)D K W SOMIRVI Ii.G(FAUL KNI R, matrker-positive serum. High PLBA (>1 () AND) M J S ILANGMAN (Department olf7hlera- I S BENJAMIN. T KRAUSZ. P t)OMIZIO, S unit Pl BA/ml) was tfound in 19/32 pancre- e(lic(.s, Universit l Ho.spital Nottinlghamil, LAZZARA, AND 1. It HiUMGART (Hepatobiliarsv aitic cancer sera. 0)/18 normials. 8/20 other Nottintg,alimii) Aspirin intaike hais been Surgery Unit and Department of Histopath- cancers. 0115 pancreatitis. 2/12 benigni and related to uppcr ga.strointestinall bleeding, ology, Hammersmith Hospital, Lonidon) 5/8 malignant obstructive jaundice. Eleven but the strength of this association has During a six year period 162 patients sus- of 32 pancreatic catncer serai had normnli renmaiined unclear. Wc haive rcported that pected of malignancy of liver, bile ducts or CA 19-9 levels but 4/11 of these contained othcr NSAIDs aire strontgly associated with pancreas were examined cytologically. One > 1 uPLBA/ml. Overall sensitivity for biccdilg peptic ulcer in the eldcrly. Wc hundred and twenty patients had proven PLBA assay was 59%' and specificity 79)' have analysed the daital from this earlier malignancy. 41 benign lesions, and one (96%/ if other cancers excluded). CA 19-9 in study with rcspect to aspirin intakc. remains uncertain. One hundred and ninety this study had a sensitivity of 66(Yo but Two hundred and thirty of "29) paitients six specimens were examined ( 118 pre- combination of the two tests improved this cged ¢>6(0 idmitted with biccding pcptic operative and 78 intra-operative). Malig- to 78%o. ulcer between 1983aXnd 1985 werc nancy was diagnosed correctly in 81/118 This ELLA is highly specific for mralig- qucstioned. Two hundrcd anld thirty cases (68-6%). Fine needle aspiration nant disease and seems likely to prove hospital controls and 2(07 of 230 community (FNA) was more sensitive (80(% true posi- useful as a test for pancreatic cancer. p(ss- controls consented to qucstioning. Paiticnts tive) than exfoliate cytology (40)%/). There ibly with CA 19-9 assay. with hiccding pcptic ulcer were more thain were no false positive results, but one twicc ais likely to bc taiking aispirin than suspicious result in a patient whose bile duct hospital or community controls with relai- stricture remains of uncertain nature. Fine tive risks (95%O confidencc limits) of 22 needle aspiration of biliary lesions had the (1-4-3-6) and 3-3 (1-8-6-2) rcspcctivcly highest sensitivity both pre- (77% ) and (GASiRO DUOFI.NAI 11 POSTi.RS (p<()-()()l McNemair's test). Thesc rcsults intra-operatively (95%/O). The overall pre- chianged little atfter cxclusion of concurrcnt dictive value of a positive result was 11)00,, Gastric mucosal bleeding: what dose of takcrs of other NSAIDs aind taikers of (98-8%Yo if the unproven case is included) but aspirin is safe? aspirin lor indigestion. Other ainilgesic the predictive value of a negative result was intakc did not viary significantly betwcen only 54%. Fine needle aspiration cytology P J PRICHARI), (G K KIIJCIIINGMAN, ANI) ( J cases and controls. Both bleeding giastric has proved valuable for pre-operative diag- IIAWKFY (Department ofj Therapeutics, aind duodenal ulccr were significantly nosis, especially in bile duct strictures, and University Hospital, Nottinighaim) Low associated with increatsed aspirin intatkc. may also aid intra-operative diagnosis in doses of aspirin are increasingly recoin- Rcspective relative risks being 3(0 (1.3-7.4) of mended for the prevention of vascular and 3 3 (1.4-8 )) (community controls). difficult cases. Palliative intubation http://gut.bmj.com/ suspected biliary tumours without tissue disease. They atre assumed to he safe but The aittributaible risk lor atspirin and other confirmation should now rarely be there is no evidence that this is so. We have NSAIDs in bleeding peptic ulccr was 35% necessary. therefore measured aspirin induced micro- (28-42%) (community controls). scopic gastric bleeding to determine the Aspirin intaike is significantly associated threshold dose for gastric injury in humans. with biceding gastric aind duodenali ulccr in Forty eight healthy volunteers were studied the elderly. Risks appear to diffcr littic from A novel enzyme linked lectin assay com- under basal conditions and after taking othcr NSAIDs. pared with RIA CA 19-9 as a serum test for aspirin 75 mg or 30)0 mg/day for five and 12 pancreatic cancer days or aspirin 1800 mg/day for five days. on September 26, 2021 by guest. Protected copyright. Mucosal injury was quantified as micro- C K CuiING AND JONATilAN M RIIODES scopic bleeding intragastric washings aspir- Effect of simulated upper gastrointestinal (University Dept oJ Medicinie aidt Waltoni ated via an orogastric tube two hours after (GI) haemorrhage on gastric acid secretion Hospitil, Liverpsool) We have recently des- the final dose. Consumption of aspirin for and G1 hormones cribed a novel serum marker for pancreatic five days increcased bleeding from ba'sail cancer: a 35x 10" D glycoprotein that values )-68()l/l() mins (95%/ confidence (G M FUILt ARiON, F. J BOYD), G P CR EAN, K expresses galactose 1-3 NAc galactosamine limits 0(42-1 12 f[l/l() minsr to 1-32 (1 (1- BUCHANAN, ANt) K 1i 1t MCCOiLi (University (peanut PNA, lectin binding). This marker 2-31) d/10() mins (aspirin 75 mg, p<()-()l) to Dept Medicine, Western Infirmairy atid when present accounts for a high proportion 2-38 (1-7-4-2) d /10 mins (aspirin 300 mg, GastroititestinIal Centre, Southernt Genteral of total serum peanut-lectin binding activity p<0.0l) and to 8X11 (5-36-1228) d/1t) Hospital, Glasgow) It is surprising that the (PLBA). An enzyme-linked lectin assay mins (aspirin 1800 mg, p<0.0 1). Values at majority of acute upper GI bleeds stop (ELLA) has therefore been developed to 12 days with aspirin 75 mg (I1-27 (0-59-2-72) spontaneously despite the aidverse aicidic quantify total serum glycoprotein gal 1-3 [d/l0) mins). and aspirin 300 mg (2-54 environment for clot lormation. We have gal NAc expression. This has been com- (2-34-995) fd/l() mins) were not signific- exiamined the effect of simulated duodenal pared with RIA for CA 19-9 antigen. antly differcnt from fivc day values. The bleeding on acid secretion and G1 hormones Sera were diluted (1:20 t)00) in carbonate bleeding caused by aspirin was dose in seven healthy volunteers. buffer pH1 9-6 and coated (16 hrs at 4"C) dependent (p<().t)5) and implies a thres- Gastric secretion was stimulated with iv onto micro-ELISA plates which were then hold for mucosal injury of about 30 mg/daiy. pentagastrin infusion ((1.25 ug/kg/h). After incubated in peroxidase-PNA (12 5 !tg/ml) Thus even the lowest therapeutic doses of 4x 15 min collections of gastric juice 41) ml after washing and quenching. Bound lectins aspirin increased the risk of gastric mucosal blood was venesected and infused directly were estimated colorimetrically. Activity bleeding in humans. into the duodenum before coatgulating Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 14()2 The British Society ofGastroenterology every five minutes for 20 minutes. Further with bleeding or non-bleeding gastric endoscopic adrenaline injection (aliquots of 4x 15 min gastric collections were obtained ulcers. 0-5 ml of 1/10000 adrenaline up to a total of after commencement of blood infusions. We conclude that patients with upper GI 10 ml) and no cndoscopic treatment. The Corrections were made for pyloric losses haemorrhage show increased fibrinolytic injection group compriscd 34 paiticnts and duodenal reflux and tany duodcno- activity in gastric juice, compared with non- (M=26. F=8; age 22-85. mcan=51 years). gastric reflux of blood was quantitated. bleeding controls. nine haid a spurter. In the control group (34 Plasma concentrations of GI hormones patients, M=26, F=8;age 17-86. mean=56 were monitored. The effect of duodenal years), 10 had a spurter. After endoscopy infusion of egg-white which has a similar The effect of submucosal adrenaline on both groups werc given intravenous H2 protein and carbohydrate content to blood blood loss from standard bleeding ulcers blockers. Endoscopy was performcd 24 was also studied. hours later and injection repeated if neces- of blood sary in the injection group. Strict criteria for After commencement infusions, S C (iiUNG, J W C LEUNG, M (iAILVINA, AND gastric acid output (mmol/h) fell to 21 4± emergency surgery werc adhered to in both w LEE (D)epartnments of'.SurgerY, Medicine 3-7 (mean+SEM) compared to 29.8±3-3 ant1d Anaesthesia, Prince of Wales Hospital. groups: (1) haiemodynamic instability over the preceding hour (p<0-02). Mean (Yo The Chiniese Universits oJf Ilontg Konig, despite 4 units of blood, (2) totail trans- inhibition was 30-4%0 (range 17-67). This Hontg Konig) To investigiate the possible use fusion of eight units, or (3) rebleeding: was due to reduction in volume and (H') of endoscopic adrencaline injection to con- haeematemesis/red aIspirate with tachycardil and was not explained by reflux of blood or trol haemorrhage for bleeding ulcers, we and/or hypotension. Initial haemostasis was duodenal juice or incomplete recoveries. studied the effect of submucosal adrenaline aichieved in 100(% of injection group. The Plasma gastric inhibitory peptide (GIP) injection group required less blood trans- injection on blood loss in a standard bleed- concentration (pmol/1) increased from ing ulcer model in dogs. fusion (3X8±2-8 units v 5-9±5-4 units, 32±2 (mean±SEM) to 66±9 following Dogs weighing 20-25 kg were ainaesthe- p<0.05) and less emergcncy surgery (5 v 14, blood infusion. Egg white did not affect acid p<0(02) than the controls. Iherc was no tised using thiopentone and anaesthesia was v secretion or GIP release. m-aintained with halothane aind oxygen. difterence in mortality (3 2). This inhibition ot gastric acid secretion by Endoscopic adrenaline injectionl is effec- L'aparotomy was performed and the blood may be mediated by GIP tive in stopping active ulcer bleeding. It intraluminal stomalch opened via an anterior gastro- and represent a physiological response to stomy. Submucosail injections of 3 ml of significantly decreases transfusion and need facilitate hacmostasis. 1/10000 adrenaline or 10% sodium meta- for emergency surgery. hisulphite (carrier substance for .adrenialine) was made in the body of the stomach. Intragastric fibrinolysis in bleeding peptic Standard bleeding ulcers were made in the Early blood transfusion promotes recurrent injected area with the Quinton ulcer- ulcer disease gastrointestinal haemorrhage http://gut.bmj.com/ maker. Ulcers miade in non-inijected areas served as controls. The blood loss in the first K 1. W1iFAIihY, VALERIE A POXON, P W )YKES, S 1) Bi AIR, R M GREENiIALGiI (INTRODUCED BY three minutes was collected by inverting the ANI) M R B Ki.iAiiiY (Departtnent of Castro- R A PARKIN) (Department.s of Slirgers' tn(d ulcer over a small dish and measured by entierologs, Genieral Hospital, Birmingham) (Charing Cross a1(id We.s- weighing. Gastroenterology, Bleeding peptic ulcer disease is a common inzister Medical School, Lotndoti) It has Mean blood loss from control ulcers problem with mortality rates of over 1)°/., in been suggested that mortality caused by (n=25) in the first three minutes was many series. Little is known, however, upper gastrointestinal haemorrhage may be 7.0±5.5 ml (SD), injection of sodium meta- about the aetiology of bleeding or rebleed- reduced by restricting blood transfusion. on September 26, 2021 by guest. Protected copyright. bisulphite (n= 15) ciaused no significaint ing in these patients. We have studied the We have assessed whether this is due to an change (6-3±4 4 ml) whercas adrenaline role of the excessive fibrinolytic activity in anticoagulant effect in a prospective (n= 15) caused a significant decrease in the gastric juice, due to duodenogastric Trypsin randomised trial. blood loss (2-9± 1.9 ml, p<0-05). Con- reflux. Gastric juice was taken from 32 One hundred patienits with severe, acute clusion: Submucosal adrcnailine calused a patients presenting with upper GI haemorr- gastrointestinal haeemorrhage were random- hage (DU-11, GU-9) and 31 control decrease in the blood loss from artefactual ised to receive either at least two units of ulcers. patients (DU-10, GU-8). Fibrinolytic Endoscopic adrenaline injection blood during the first 24 hours of admission, may have a role to play in endoscopic activity of aspirated gastric j uicC was or no blood unless their haemaglobin was haemostasis. assessed using fibrin plates. and Trypsin less than 8 g/dl or they were shocked. Minor assayed using a colourimetric method. bleeds and varices were excluded. As hyper- Fibrinolytic activity was found to be present coagulation cannot be measured using in 20 patitents (63°/0) with upper GI bleed- Randomised controlled assessment of endo- conventionial coagulation tests, fresh whole ing, and only four (1 3%) of controls scopic adrenaline injection for actively blood coagulation was measured by the (p<.)()()5). T rypsin was detected in all bleeding ulcers Biobridge Impedance Clotting Time (ICT) gastric juice samples showing fibrinolysis. and the results expressed as mean ±SEM. Fibrinolytic activity was present in 22 out of J W LEUNG., C S CHUNG, R 1 STiT1L, AND The ICT on admission for the transfusion 29 samples with pl->4. and only two of 34 at T J CROFTS (Combined Endoscopv Uniit, group (n=50) was 44+±0)3 mins (normal lower p11 (p<()f()()5). Fibrinolytic activity Prince of Wtales Hospital, The Chinese range 8 12 mins). This hypercoagulable was scen in six of 11 patients with bleeding Univer.sitv of Hong Kong, Hong Kong) state was partially reversed by eairly blood DU (55%), but only one of 10 control DU Sixty eight patients with actively bleeding triansfusion to 64±t)-3 mins at 24 hours patients ( 10% ) (p<().025). There wias no (spurting or oozing) ulcers at emergency (p<0(001). The 50 allocated to receive no significant differcnce in librinolytic activity endoscopy were randomised to receive blood had ai similar ICT on admission of Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society of Gastroenterology A 140)3 4.7+±04 mins but the hypercoagulable state atrophy may bc caused by reflux gastritis or (WCC) is normal (< 12 x 1 /1). The imr1port- was maintained with ICT at 24 hours of to a reduced trophic effect of gastrin on the ance of the ealrly scani (three to lour hours) 4-3+±0.4 mins. Only two patients not trans- gastric body mucosa. In order to differenti- and the use ol mIixed leucocyte preparations fused rebled compared to 15 in the early ate between these mechanisms, we prospec- in patients without a ICLucocVtosis has not transfusion group (p<0)-001). Five patients tivelv studied serum concentrations of bcci established. We have evilulted 101 died, and they were all in the early trans- pepsinogcns A (PgA) and C (PgC) before scans in 81 patienits with suspected intra- fusion group. and 10 days, 1/ year, and one year after abdominal sepsis to assess (a) the diagnostic These findings show there is a hyper- subtotal gastrectomy in 22 patients, 11 of accuracy of the early scan (three to live coagulable response to haemorrhage which them randomly selected for Billroth 11 and hours) and (h) the relationship ol the blood is partially reversed by blood transfusion 11 for Roux-en-Y anastomosis. Serum PgA lcucocvtc counlit to thle scilsitivitv of I [S. leading to rebleeding. and PgC levels were measured by radio- lThe positivity of Il S was conlfirimied hv immunoassay. operation or spontaileOLiS dischairge of ptus Fasting bile acid reflux was increased ind negativity by recovery of the paitienit Laser doppler assessment of human gastric from 10±0)5 [tmol/h before to 121*4±75.8 without further surgery. blood flow [tmol/h after Billroth 11 resection (p=0-01), In only four of 73 patients with hoth early but was reduced by the Roux-en-Y pro- and latte scans wais interpretation altered hy P M Al LEN, I CIIiESNER, K WHEAIL EY, AND M cedure from 0(6+±04 stmol/h to 01 ±01-1 the late scan. Twenty two of 23 scans in GOLDMAN (Department.s of Surgery anid stmol/h (p=0-02). Serum PgA showed a paitients with a normail WC C were coni- Medicine, University of Birmingham, progressive reduction with time, indepen- firmed cliniclily but with a WCC of Birmingham) Necropsy injection studies dent of the type of surgery; 115+9 tsg/l >20x 10()/1 five of 30 scans were equivocal1 or have shown that the ulcer prone areas of the before and 87±13 [tg/l 1i) days (p<0().5), gatve false results. stomach and duodenum have fewer 75+±1) tg/l 112 year (p<0-05). aind 39+6 It is concludcd that the early scan is mucosal arterioles, but physiological [tg/l one year (p<)-()l) after Billroth 11- diaignostic in most caises but 1f It Is neICtgivc evidence of poorer perfusion is lacking. resection, and 95+8 ftg/l before and 67±8 or equivocal late scanning is recotiieidided. We have studied 19 patients, median age tg/l It) days (p<0)-05), 53±8 (tg/l '12 year A normal WBC does not exclude the use of 7t) (range 27-83) using the non-invasive (p<0(05), and 20)±2 ,g/l one year (p<.(Ol) this investigation and special preparation Laser Doppler (LD) technique. Flux after Roux-en-Y surgery. There were no methods are not needed. Very high WB3Cs measurements were made during gastro- significant differences between the two can be paradoxically -associated with diag- scopy under diazepam sedation, using the groups of patients. Serum PgC levels nostically inaIccurate scans. Periflux Pf2 instrument. Readings were remained unchanged and the serum PgA/ made at 9 sites: distal oesophagus, proxi- PgC ratio was reduced in parallel with the mal, mid- and distal stomach on greater and reductions in serum PgA. This study reveals a progressive decreaise Impaired gastric adaptive relaxation in http://gut.bmj.com/ lesser curves, and pre- and post-pylorus. patients with postvagotomy diarrhoea In all cases, the stomach was macro- in serum PgA after gastrectomy, indicating scopically normal. Flux varied from 40±28 progressive mucosal atrophy of the gastric remnant. As this decrease in serum PgA M N HARI I.IY ANI) ( R MA(Ksit (UnIiI'-rSiltV V (mean±SD arbitrary units of flow) in the Royal antrum to a maximum of 92+35 V on the could not be precluded by prevention of Department of Sutrgers', Liverpool enterogastric reflux by Roux-en-Y anaisto- Hospital, Liverpool) Gaistric idaIptivC lesser curve. In the proximal stomach, the relaxation is said to he mean value at each site exceeded 70) V mosis, we suggest that this atrophy results (GAR) impaired whereas none of the five distal gastric sites from a reduced trophic action of gastrin ifter truncal vagotomy and drainage of GAR after may on September 26, 2021 by guest. Protected copyright. had a mean value above 56 V. Overall flux because of the removal of the antrum. (TV+ D). Ioss vagotomy in the stomach at 77.5±39.8 V was contribute to the excessively rapipd gastric proximal emptying exhibited by patients with post- significantly greater than that of 48X5± in 31-2 V in the antrum and vagotomy diarrhoea. We studied GAR pylorus (p<0-00( Diagnosis of occult intra-abdominal sepsis 1) healthy subjects (mean age 29 years, Student's t test. This in vivo demonstrates marked with "'Indium labelled leurocyte scanning range 22-4(), and 17 paitients. six mouiths to study (ILS) - early versus late scanning 17 years after TV+D (mean age 54 years, regionality of blood flow in the stomach and 39-65 of whom six had duodenum, being least in the ulcer-prone range years) patients SARAII C t1 BARBEIR, M C areas. CIlESiLYN-CURTIS, persistent postvagotomy diarrhoea. AlDi)RIDGE, I) A CUNNINGHAM, ANI) 1i A F Fasted subjects were intubated with a DUDLEY (Academnic Surgical Unlit and Ryle's tube with a flaiccid plastic bag (800 Department of Radiology, St Mary'.s ml) attached and containing a pressure Prospective study of the effect of partial Hospital, Londoni) Intra-abdominatl scpsis microtransducer. Gastric corpus-fundus gastrectomy with Billroth-II and Roux-en-Y remains a major causc of morbidity and pressure waIs recorded during distension ol anastomosis on serum pepsinogens mortality in surgical patients. ''llIndium the bag with 460)±30 ml (mean+SD) ot air labelled leucocytc scanning is an established over 30 sec. Pressure indices (P1) were J B M J JANSEN, P N M A RIEFU, I BIUMOND, If J M method of diagnosing occult sepsis but its derived (areat under curve: mean of four JOOSTEN, AND C B H W LAMERS (Dept Gastro- major disadvantage compared with ultra- readings) aind compared. enterology and Hepatology, University sound or computed tomography is the PI cm H1O (mean+SD) were: Controls Hospital Leiden and Dept Surgery, CWZ, significant delay beforc a result is obtained. 11 7+3(0 v TV+D (without diarrhoea) Nijmegen, The Netherlands) Subtotal This has been reduced by faster labelling 15 4+2-2 v TV+D (with diarrhoea) gastrectomy is usually followed by mucosal methods but pure granulocyte preparations 21l2+3 6 (p<0O01 ANOVA). atrophy of the gastric remnant. This are advocated when the white cell count This confirms GAR is significantly Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 14()4 The British Societ7 of Gastroetiterology impaired after TV+D and the degree of ulcer (DU), 94 for pyloric or prepyloric A randomised, controlled study of adjuvant impairment is significantly greater in ulccr (PU/PPU), 71 for gastric ulcer type I Tamoxifen in the treatment of gastric patients with diarrhoea thain without. (GU) and 28 for combined ulcers (GDU). carcinoma Complete follow Lip wis achieved in 85-4`%, 55"` of which had routine cndoscopy. J D IIARRISON, I) 1. MORRIS, 0 Fils, -I JONF.S, len ycirs' total recurrenice raite (includ- AND) I JACK(SON (Department of Surgerx'v Highly selective vagotomy (HSV) in the ing aisymptomatic recurrences) was 20'4% UniiversitY Hospital, Nottinighiamlte) To treatment of acute complications of peptic for DU 32% for PU/PPU, 198) for GU investigate the effect of Tarmoxilen in ulcer and 317"% for GDU. Complcte vagotomy paitients with gastric cancer, 100 patients as aissessed at operation by at modified were raindomilised after stratilication to M RM(EiRS, I) JOIINSTON, J N PRIMROSFI, I) C Burge-Test significantly lowered the recur- treaitment or control groups. 'Ihe treatment WARI), R 1. BLACKFETI, ANI) M J MCMAIION rcncc rfatc for DU to 13-6%). In PU/PPU a group received 4t) mg laimoxifeni dailly aind (University' Depa(rtment of Sutrger_y, The drainage procedure significantly improved the patients were followed up tintil deaith. G,enerdl Infirma(ry, Lee(ds) Sincc the advent the outcomc ( 16'6%° with versus 39%, with- The mediain survival in men was 25-5 weeks of the H2-reccptor antagonists, elcctive out drainage). At 1) years Visick gralde I in the control group and 15 5 weeks in the surgery for pcptic ulccr (PU) has become iand 1I wias found in 88%. of the DU, 84% of treaitment group. whilst armongst the lcss common. The complications of PU. the PU/PPU, 73%. of the GU and 82', of women, the mediian survivail in both groups howevcr, continue unabated. the GDU. wats 25 weeks. Fo investigiate the efiect of Highly sccctivc vagotomy is the best The ovcrall symptomatic result 1t) years oestrogen receptors on prognosis these cicctive surgical treatment for PU but what aifter PGV is good in all ulcer types. The paticilts tumours had oestrogen receptor proportion of paticnts with acutc complica- chaincc of cure is 80%O for DU and surpris- status measured. Ihe overall cumulative tions can be trcatcd with H:SV, and how ingly for GU. but unsaitisfactory in PU/PPU survival in patients who were oestrogen eftectivc is it in curing the ulcer'? Thcsc are and GDU. 'Ihc outcomc is significaintly receptor negative (ER -) was significantly vicious ulccrs and onc might expect the improved by an intraoperativc complctc- better thain in those piatients whose tumours incidenicc of rccurrcnt ulccr (RU) to bc ncss test in DU alnd by a drainage proccdure expressed oestrogcii receptors (ER+1), higher aftcr HSV for complicated PU than in PU/PPU. particulatrly in the femalle group. The after clective IISV for PU. mcdian survival in ER+ women wa1s 185 Since 1969. 985 paticnts havc undcrgonc weeks compared to 33 weeks in the ER- H1SV in this department of whom 127 (13%) women (Logranik test p<0)(01).() The underwent [ISV for acutc complications of median survival in men was 20 weeks lor PU (perforation - 70, haemorrhage - 57). Asbestos: a possible aetiological cause of ER+ patients and 22 weeks for ER- Highly sclective vagotomy was used in 33%! gastric cancer? Thcse studies show thatt the presence ol of pcrforated PU's and 45% of bleeding oestrogen receptors in gastric carcinoman is http://gut.bmj.com/ PU's. Overall mortality was I ("o (perforated P W J IIOU(II'ON, I STEIWART, P iHiAP, N J MCC an indicator of poor prognosis in women, PU- 0%, bleeding PU - 2%). Incidence of MORTINSEN, ANt) R C N WIllTlIAMSON (Depart- and suggest that sex hormone manipulation RU was 13% for perforated PU's, 2% for ment of Surgery, Bristol Royal Infirmary in men may have a role in the trea.tment of bleeding PU's (overall 8X/) - no different and Department of Anatomy, University of gastric carcinoma. from electively treated PU's. Visick grad- Bristol, Bristol) There is some epidemio- ings were not significantly different from logical evidence to suggest that workers patients with PU's treated with elective exposed to asbestos have an excessive HSV. In conclusion, HSV can be used in mortality from gastric cancer and it has been C-myc oncogene product expression in on September 26, 2021 by guest. Protected copyright. patients with acute complications of PU, postulated that the high incidence of gastric benign and malignant gastric epithelia and with careful case selection it carries a cancer in Japan may be due to contamina- low mortality, low risk of RU and gives a tion of their polished rice by asbestos. W 11 AlTlUM, K M NEWBOTLT), F MACD[)ONAiL[), good quality of life. Scainning electron microscopy was per- B RUSSETLL , AND i J SI'OKES (IN TROD)UCTH) BY formed on specimens of stomach taken M R B KEi(GiLEY) (Slurgical Immnunology Unit from six patients with histologically proven and Department of Pathology,, Queen gastric cancer and on three patients under- Elizabeth Hosspital, Edgbaston, Birming- Clinical results 10 years after proximal going gastric resection for benign disease. ham) Amplification of the C-myc oncogene gastric vagotomy In five of the six patients with gastric cancer has been described in gastric cancer. In this unknown fibres were found in the tumour study the expression of the oncogene pro- C MULLER, R IE'(IIMANN, P Vi-RREE'lI, B tissue and in one patient in the premalignant duct, p62 C-myc, has been assessed in both IIUSEMANN, 1. FIEDI)ER, ANI) B F NGLKE (IN'TRO- mucosa surrounding them. Simultaneous benign and malignant gastric cpitheliai to 1)U1CE D) BY .1 11 BARON) (Dept of SurgerY, radiographic microanalysis of these fibres determine whether C-myc is important in Kanitonsspital, CH-4031 Basel, Switzerland) has shown them to contain silicon, mag- gastric neoplasia. Histological sections of a To assess long term results of proximal nesium, calcium and iron and their molar range of benign and malignant epithelia gastric vagotomy (PGV) sufficient numbers ratios strongly mimic the known x-ray ele- have been examined in an immunohisto- of patients actually followed-up for 10 years mental profile of tremolite asbestos. No chemical assay using a monoclonal antibody or more are needed. We report on a pro- fibres have been identified in any of the to p62 C-myc. In the benign tissue, staining spectivc multiccntre trial on PGV initiated control tissue. was cytoplasmic. All tissue types showed in 1974. These findings suggest that mineral fibres some staining but gastritis was more Betwcen Jainuairy 1974 and April 1975 717 might play an important role in the patho- commonly positive than normal epithelium. patients underwent PGIV: 524 for duodenal genesis of gastric cancer. This was particularly marked in atrophic Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Societv ofGastroetnterology A 1 405 gastritis showing type 2b intestinal meta- Analysis of dyspeptic symptoms to deter- paiticnts with aictivc duodenal ulccration plasia. There was no diffterence between mine rick of gastric cancer and priority for (DU). Using ai pH clectrode indirodLuced active and quiescent chronic suLpcrficial endoscopy through an eiidoscope. iiucosail and luiriaiit. gastritis suggesting that staininig was not p1lI wais meaiistired in situ in the Itilltius, simply demonstrating proliferiation. In a 1 M CHISIHIOI.M,( B.1 UNWIN, A ( MOR(F AN. AND) aintruni, duodenall Ceap aiid loop bcfore aiiid significant proportion staining was limited ( R (ill- 1S (.St JaInleS'S Hosp)iatl, Leed.s and(l during perfusioi with phosphaitc (p11 1 5) to the tips of the mucosal fcolds, sites not A ire(lale Hospital. Keighley, Yorks) Scrccn- hulffer. 13efore icid perf'usioii, the duodenal usually considered to be actively dividing. ing for early gastric c Gncer(EGC) by gastro- iiiucosaIi pHl wats higher (p<0f-00l1) in DLJ This was most marked in type 2b intestinal scopy in all middle-aged piatients with a two (72±0( 1 ) thain in controls (6118+(1 ). metaplasia. In tumours, less than 40(% of wcek history of dyspepsia has recently beci D)espite comrlprablc 'Lfuiail lLnlllililil ieCidity specimens stained positively. When present advocatted. Unfortunately a 2-4A" yield of' in conitrols (24±0-.5) ndi DLJ (18±0 I), staining was unreliated to differentiation. ciancer with at 98% false positivc rate arose. lurniiril p1 wais morc ailkialinc (p<()()I5) in although there was a suggestion of We hiave attempted to further define risk of the duodeOnld loop in DU (78X()1) thlin ini increased positivity in intestinal type cancer and there'ore priority t'or endoscopy the coiitrols (7.4±()02). Acid perfusioii lesions. C-myc may he important in the in dyspeptic patients by analysis of their reduccd (p<()0()0l) mucosail p1H in the progression to gastric malignancy and may symptoms. zintruLii, duodeciail cap aind loop in DU regress oncc malignant change has The relative incidence of symptonis in 10(1 (ApH= 1 1+±04, 1 3±0-3, 1-1±0-2) but not occurred. paitienits with glastric cancer (2(1 EGC), 164 in controls (Apl0=()2±0()1, ()0()7+0()()8, with benign upper gastrointestinal condi- )- 1 +()-()7). During icicd perfusiosIn, MUCOSa tions and also in 30)0 middle-aged randomil pH wats lowcr (p<()()l ) in the duodcnal calp population controls werc rccorded. A arnd loop in DU ptittenits (5.8±0(.3, 6(1±0 1 simFple scoring index wias then produced by than in the conitrols (6-8±011, 6(7±() 1). Use of CA-50 in the differential diagnosis of applying the Log Likelihood Ratio statistic [Ihe rnucosal alkalinity observed in DU, benign and malignant diseases of the to these symptom frequenicics to prcdict not mniiintnied diuriiig aicid chal clegc. stomach and oesophagus 'high risk' of cancer (defined ats probability suggests that riiucosal bicarboiiate secrctionI >0-05). Eighty one cancer patients wcrc is ait ai maximium drive in DU and the S B KFl-llY, M J HEiRSIHMAN, N A IIABIB, R C N above this value with only a 6% fialse CaIpaIcity to niutratlise fully ain aicid surgc WILt.IAMSON, J SPE.NCER, AND C Bt WOOl) positive rate, giving a 74% yicld for cancer. seeriis limited. (University' Departmenit o)f Surgerv, Bristol [o determine its clinical significaincc, the Royal In/irmarv, Bristol acnd Department of scoring indcx was recordcd in 300 consecu- Surgery, Royal Postgraduiate Medical tive dyspeptic patients and was compiared School, London) I his study investigated with a cliniciains evaluation of cancer risk. the role of the tumour marker CA-5() Fifteen of 16 gastric cancers (4/4 EGC) were Increased formation of leucotriene U.4 http://gut.bmj.com/ (carcinoma associated antigen) in the predicted by the index but only 9/16 were (LTC4) in campylobacter pyloridis (CP) - differential diagnosis of benign and felt to havc canccr by the clinician. The associated gastritis malignant diseases of the stomach and seiisitivity, specificity and yield for ciincer oesophagus. Serum was collected from 5() by the index compares well with the A AIIMIFI), 1) VNIRA, S K CIRNS,( H01lTON, M controls, 19 with benign oesophagogastric clinician's. Fii ZON, A POt' YI)ORUS, ANI) P R SAL1MON disease, 24 with gastric carcinoma and 21 A simple risk index for gastric ciincer (Dept (Gastroe,nterolosg, MicrobiologY, with oesophageal carcinoma. A radio- using symptom analysis cain predict cancer Histopatholog/,, The Middlesex Ilospital, immunoassay (RIA) was used to detect Lonldoni) Vhe prcsciicc of CP in the risk as accurately as a clinician, with a high pgstric on September 26, 2021 by guest. Protected copyright. CA-5) in the serum and a level of 17 yield per endoscopy, and maiy therefore bc at mucosa riay bc aissociited with inflmrni-am- units/ml was used as a cut-off between useful atid in determining priority for endo- tory cell infiltraltion aid colisequcilt alter- benign and malignant disease. All 5S) scopy when screcning for EGC. tion in l TC-4 aid prostaglaindini (PG) E. normal sublects and 18 of 19 (95'Y1) with levels which could play ai proinflariimatory benign oesophagogastric disease had CA-5) role. levels below 17 units/ml. In the cancer Antral biopsies of 1 3 (yspeptic patients groups, 18 or 24 (75°/) with gastric were incubated ait 37"C in pre-wairmed/ carcinomai and 15 of 21 (71"%) with oeso- Ability of duodenum to maintain a neutral oxygenated Tyrode Solution (baisail recliesc) phageal carcinoma had CA-5( levels above pH microclimate in response to acid aind tramnsferred to sccoInd incubation 17 units/ml. Therefore, the sensitivity is challenge in endoscopically normal and rnediuni containing ioiophorc A23 1 87 73"% (33 of 45) and the specificity is 100%, duodenal ulcer subjects 5 Itg/ml (stiriulated relcase'). Superriatant (5(t of 50) and 95% (18 of 19) for the control cicosanoids were riieisured hv radiod and benign groups respectively. In patients B J / DANESII, 0 STARK, J M RAWI iNGS, M 1. immunoaissiay. with tumours and values above 17 units/ml, ILUCAS, ANt) R I RUSSEI.II ((Ga.stroenterology' Eight patients haid acute gstritis (intral the mean concentration of serum CA-50 Unit, the Royal Infirmnarland Department CP prcsenit in atll) aind fivc haid normil aitral was 65+33 (range 31-132) for the gastric oJ Physiolo,gy, University oJ Glasgow, histology (no evidencc of CP). carcinomas and 58±30 (range 19-116) for Glasgow) It has recently been shown in man Baisial reiclsc (pg/mgww/2() min, macics+ the oesophageal carcinomas. These data that gastroduodenal mucosal surface is SEM) of LTC4 aind PGE, in norml suggest that the CA-50 RIA test could be of lined by a near-neutral pH mnicroclimatc. (74±11.3 aind 1691±336.2) aind ihbnormil use in the differential diagnosis of benign Wc measured duodenal mucosal surface pH inucosai (94± 14-2 arnd 1824±331)3) were and malignant diseases of the stomach and on direct acid chcillenge in 11 endoscopicailly similalr. Stimulated release of l TC,1 oesophagus. normal subjects (controls) and in 11 (147±21-1) wias signilficaiitly cnhainced corii- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A14()6 The British Society ofGastroenterology pared to basal levels in gastritis (p<(0)5). nists. To evaluate onset and duration of H- 20(6±2A3, 21 4±7-3, 13-6±2-1 mins). Stimulated LTC4 in abnormal mucosa was receptor antagonist action in relation to Gastric solid cmptying had two com- significantly greater than normal mucosa smoking habits, we tested the effect of ponents, both of which were prolonged by (81±9 2, p<0)05). Basal and stimulated ranitidine (RAN) and famotidine (FAM) smoking but not gum. An initial lag phase PGE, levels in normal versus abnormal under physiological conditions, using (mean baisal, 184±2 7, smoking, 28+5-7 mucosa were similar. ambulatory pH-metry. Intragastric pH was (p<0(05). gum 18+3 3 mins) and a subse- These results suggest that LTC4 forma- measured over 20 hours. Each of 18 heallthy quent linear emptying phase (mean basal tion may be of greater importance than volunteers. 20-36 years. nine smokers and 1(07±0+13, smoking 0(85 ±)009 (p<0(05), PGE. synthesis in CP associated acute nine, age and sex matched non-smokers, gum 0(98 ±009o(Y/min). No episodes of gastritis probably reflecting inflammaitory received either 40 mg FAM, 300 mg RAN GOR were observed. cell infiltrate. or Placebo in a double blind, randomised Gatstro-ocsophageail reflux is associated study as a single evening dose, 1800. With with delayed solid but not liquid emptying both drugs 20) hours acidity was markedly aind our findings suggest a mechanism for Comparative study of 4-hour rapid urease suppressed. After FAM treatment mean the observation that smoking exacerbates test (RUT) to culture and histology for the inhibition in smokers was 42°/., in non- symtoms in susceptible individuals. detection of Campylobacter pyloridis (CP) smokers 76°/o, with RAN 60%, and 67% in gastric and duodenal biopsies respectively. When areas under the pH- curves from each individual were calculated and treatment compared to placebo Mucosal repair of rabbit duodenum: role of D VAIRA, J iJOLfON, M FAILZON, A AIIMED, S R an alkaline micro-environment CAIRNS, AND P R SALIMON (Dept of Gastro- (=1()00%/,), with either drug response was enterology, Microbiology, Histopathology, smaller in smokers than in non-smokers (FAM 153±21°., versus 214± 19'%, p<0(01, W FFill, P KARNER, S KIiMESCII, M STARLINGER, Middlesex Hospital, London) The clinical ANI) R SCHIIFSSEI (INTRODUCED BY A GARNER) significance of CP in gastroduodenal biop- RAN 176±21/, versus 232±29°/, p<0.05) during the first four hours after drug intake. (Surgical Dept 1, Univ ('linic of Vienna, sies is uncertain. The aim of this study was A-1090 Vienna, Austria) The duodenal to evaluate the sensitivity and specificity of A similar effect was observed in the morn- ing period from 6-100t) (FAM 118±19% mucosa of the rabbit has the ability to repair the four-hour RUT to histology and CP itself rapidly after acid injury. In this study culture in the detection of CP in gastro- versus 20)6±19'(o, p<0(001, RAN 133+ 21% versus 207±31%S, p<0(02). During we investigated the importance of nutrient duodenal biopsies. bicarbonate and of the layer of necrotic Gastric and duodenal biopsies from 24 night time there were no significant differ- ences. tissue (=alkaline micro-environment) for dyspeptic patients were homogeinised in the repair process after acid damage. 0-9% saline and immersed in 2°/O urea These results indicate that smoking impairs onset and duration of response of Mucosal sheets of rabbit duodenum broth. http://gut.bmj.com/ both drugs tested. mounted in Ussing-chambers were exposed Biopsies from 16 patients (66.6%0) to 10 mM luminal acid for 10 min. After showed evidence of gastritis and/or duo- injury the luminal saline solution was either denitis, despite 5 showing no macroscopical adj usted to pH -=7 4 or pH1 =3 and the abnormality. All these 16 patients showed Smoking delays gastric emptying of solids nutrient solution contained either 25 mM CP on histology, indicating a high correla- HCO- or HEPES. In some experiments acute tion between the presence of CP and G MILLER, C FARRIN(G[ON, V SMITH, M V the necrotic layer was removed by scraping gastric and/or duodenal inflammation. MERRICK, AND K R PAL MER (Departmnentls of (RNL). Tissucs were allowed to recover five Determination of the sensitivity for RUT Nuclear Medicine and the Gastrointestinal hours after injury. We measured: alkaline on September 26, 2021 by guest. Protected copyright. to histology and culture was 81l3'Y0, 56.3°/0 Unit, Western General Hospital, Edin- secrction (AS), potential difference (PD). and specificity was 1(N)% and 100(°/ burgh) The effects of smoking upon oeso- and performed histology. respectively. phagogastric transit were defined in eight Acid exposure caused a 67%/ drop in PD This study shows: (1) Even when no healthy volunteers by radionuclide scanning (from 2 9 to t)9 mV), a 28%M increase of AS macroscopic abnormality is found at endo- an ingested test meal. Oseophageal clear- (from 0(67 to 0-86 r&Equ/cm2- 1() min) and scopy of dyspeptic patients histology and ance was measured by examining three damage of 950O of villi (n=48). After five four-hour RUT may reveal antral CP. (2) areas of interest during a liquid swallow of hours morphometry showed repair of 72% The four-hour RUT can provide a rapid and In"' labelled water and during a semisolid of villi (HCO -, pHl -=74), 52% (HCO3-, useful method for the assessment of acute swallow of Tc'"1 labelled omelette. Gastric pfi =3), 69%X (HEPES, pH1 =7 4), 0%Yo gastritis and/or duodenitis in dyspeptic emptying of the swallowed test meal was (HEPES. pH _=3), 52%° (HCO -, patients. then mcasured by a standard double count- pH1 =7-4, RNL) and 27% (HCO- ing technique. Finally valsalva and postural pH, 3. RNL) respectively (n =8, ech manoeuvres werc used in an attempt to group). Smoking and pH-response to H2-receptor provide gastro-oesophageal reflux (GOR). The absence of nutrient HCO- did not antagonists Each subject was studied under basal con- impair the repair process at pH[ =7-4 but at ditions, whilst continuously smoking and pH, =3. RNL delayed repair at pH, -74 C-C SCFHUERER-MAIY, 1 VARGA, H R KOEL1/, then whilst chewing nicotine gum. but prevented this process almost com- AND F HiALITER (Gastrointestinal Unit, Oesophageal transit was unaffected by pletely at pH1 =3. University Hospital, Inselspital, Bern and smoking or gum (mean basal liquid transit We conclude, that mucosal repair in the Gastrointestinal Unit, Triemnlispital, Zurich, 7 5±1 (SEM) smoking 66± 1, gum 6 3±1 duodenum is dependent on the presence of Switzerland) Smoking has been shown to sec). Gastric liquid emptying was cxponen- the necrotic layer and the availability of impair the effect of H.-receptor antago- tial and unaffected by smoking or gum T'/2 nutrient HCO-. Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from The British Society ofGastroenterology A 14()7 Synthetic secretin secretolin (SS): an duodenal ulcers which had failed to heal in returned during the next acid infusion. 1'hus adequate substitute to GIH natural secretin two months or more. In all patients, gastric our data indicates that acidification of the (NS) for secretin provocation test in secretion was completely aibolished during duodenum may slow gastric emptying by Zollinger-Ellison syndrome (ZES) the night, from which we conclude that causing reproducible reversible inhibition resistance of the ulcer to heialing is not due of antral pressure activity, increasing M MIGNON,. IFLOUAER-IBLANC( D RIGAUD. P to failure of nocturnal giastric inhibition. pyloric resistance and reducing duodenal RUS/NIFWSKI, T CHIEIVAIEIIR, 1 VAI1OT, J Eight patients with nonhealing duodenal coordination. VATIIR, E RENFI, AND M D)UET (Service 1ti ulcers underwent two 24 hour studies of Gastroenterologie, Hopitial Bichat, Paris gastric secretion. On one day, the patients and Laboratoire de Radioitnmultnologie, received 15t) or 30)0 mg ranitidine at 10)0( h Reproducibility of 24-hour studies of intra- Hopital Lariboisiere, Paris, France) and 220)( h and standard mealls were eaten gastric acidity, nocturnal volume, acid and Synthetic secretin secretolin is equipotent at 080)X, 1300, and 1800 h. On the second pepsin secretion by the aspiration method. to NS on gastrin release in control and study day, patients were fasted throughout duodenal ulcer (DU) subjects (1987) but the 24 hours, except for the two doses of M DFAKIN AND J G WIllIAMS (Department oJ the comparativc efficacy of SS for ZES ranitidine, as previously. Gastric aicidity Gastroenterology, Royal Naval Hospitial diagnosis was not assessed. As GIH NS will was significantly less inhibited between Haslar, Portsmouth, Hants) Whilst 24 hour no longer be available, both Hoechst SS and 14()0 and ()1 00 h when meals were eaten. study techniques have been widely used in NS effects on acid, gastrin secretion were Nocturnal (00 00-08t)(0 h) gastric secretion the evaluation of antisecretory drugs there evaluated in 10 unoperated ZES (53± 13 was similarly inhibited on both study days. has been no previous formal assessment of years) and 13 DU (43+ 16 years). In We conclude that food significantly inter- reproducibility. randomised sequences 3 CU/kg SS and NS feres with therapeutic gastric secretory Eight volunteers with duodenal ulcers in were infused for one hour after antisecre- inhibition. It seems to us that this remission were studied during two 24 hour tory drugs withdrawal for three days. Serum phenomenon contributes to resistance of periods using a size 10 French sump type gastrin (SG, pg/ml), acid output (AO, some ulcers to healing with ranitidine. We nasogastric tube. Three standard meals of mmol/h) were measured simultaneously: have therefore healed resistant ulcers 375 ml of clinifeed with one Oxo cube in 2()() four SG samples and one hour AO were within 14 days by withholding food and ml of hot water were taken during each 24 obtained before and upon secretin infusion. administering nutrition parenterally. hour period at ()X8)(), 1300), and 18X)0 hrs. Parametric or non paratmetric paired-data Gastric aspirates were taken for pH record- analysis was used according to results distri- ing at 15 minutes after each meal for three bution. In ZES: basal AO (BAO) was Human hours and half hourly between meals. 25±11; AO rose more on SS (AO; 35-4+ antropyloroduodenal motor activity the after intraduodenal acid infusion During night the stomach was kept 15) than on NS (AO: 31-+816); difference empty by a continuous, intermittent BAO versus (v) AOSS and AOSS v AONS: positive pressure, aspiration pump. http://gut.bmj.com/ p<)-05. Basal SG (BSG) was 219 (84-7813) D D KERRIGAN, 1t A HOUGHTON, N W READ, AND The intragastric pH profiles were virtu- and increased more on SS (SG: 950, 118- A G JOHNSON (Dept of Surgery and Sub-Dept of Human Gastrointestinal ally identical on both days in all eight 18769) than on NS (SG: 834, 92-12(012); Physiology and subjects. For each patient pH scores for the difference BSG v SGSS and SGSS v SGNS: Nutrition, University of Sheffield, Sheffield) 24 hour period varied by 6-8%". (0)-21%); p<0-05. In DU: BAO was 9-7±6-5; AO A manometric catheter was used to record pressure activity in median (range). Nocturnal volume, acid decreased more on SS (AO: 0-57+ 1-1) than the antrum (three sites), and pepsin secretion were more variable. on NS (AO: 128± 1-25); difference BAO v pylorus and duodenum (four sites) in 12 healthy fasted volunteers during intraduo- Median percentage differences between AOSS or AONS: p<0)-)01. Difference days 1 and 2 were: acid output 36%, (2- on September 26, 2021 by guest. Protected copyright. AOSS v AONS: p<0(05. SG was denal infusion of normal saline and isotonic )- I M HCI. Pyloric pressure 661%); pepsin output 80X% (35-210%)); unchanged by both SS and NS. Thus com- was recorded pepsin concentration 41% (0-93%) and pared to NS, SS induced higher inhibition of using a 4 cm long sleeve sensor positioned by measuring the transmucosal volume output 50% (5-153%). AO in DU, higher increaise in AO aind SG in PD at either Intragastric pH is the most reproducible ZES and can be confidently substituted to end of the sleeve. Intraluminal pH was measured in the terminal and most convenient parameter for the NS for ZES screening. *(M±SD) antrum and at two study of a drug effect. Outputs are more positions in the proximal duodenum. Saline variable making measurements for an indi- and acid were infused into the duodenal vidual bulb alternately for consecutive 30 minute patient unreliable. periods for up to three hours at both I and 2 ml min. During acid infusion there was (1) GASTRO D)UOD[NAI POSrFERS III a significant reduction in the frequency of Effect of meal temperature on gastric empty- antral pressure waves [acid, 8h (0-54h ') ing of liquids in man Food is bad for ulcers median (range); saline, 87h (10-272h '): p<0.011, (2) a marked increase in pressure W M SUN, 1 A HOUGHTON, N W REA[), D 1) A JOHNSTON AND K G WORMSLEY (Ninewells waves confined to the pylorus [acid, 18h-X GRUNDY, AND A G JOHNSON (Dept ofSurgery Hospital, Dundee) Inhibition of nocturnal (6-128h l);saline, 2h '(0-14h '): p<0)-01, and Sub-Dept of Human Gastrointestinal gastric secretion is thought to be the most (3) a reduction of coordinated pressure Physiology and Nutrition, University of important factor in determining the healing waves involving the duodenum [acid, 13h Sheffield, Sheffield) The existence of of duodenal ulcers. Overnight gastric secre- (0-50h '); saline, 45h (24-70h '): themoreceptors, responding to tempera- tion was measured after an oral dose of 300 p<0001. These changes were reversed tures of 1()-1 2°C and 46-490C in the mucosa mg ranitidine at 22 00 h in nine patients with during subsequent saline infusion but of the stomach and duodenum suggests the Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A1408 The British Society of Gastroenterology possibility that the temperature of food may first test (p=NS, r=0-65). The presence of inexpensive and safe test for the diagnosis influence the rate of gastric emptying. Intra- NGT did not affect DGR significantly. of alkalline reflux gastritis. shows good gastric temperature from two sites and DGR-HIDA was found to correlate correlation with measurement of entero- gastric emptying rates were measured con- significantly with DGR-NGT (p<()-()()l for gaistric reflux using "Tc-HIDA. tinuously in six normal volunteers after both peak and post prandial DGR). When ingestion of 400 ml radiolabelled orange DGR-HIDA and DGR-NGT were juice at either 50, 37, or 4°C. The highest mcasured simultaneously correlation was Gastric and duodenal subnuclear vacuolated (43±()±0(4°C, mean±SEM) and the lowest excellent (r=O-88, p The British Societv ofGastroenterology A 1 409( evaluated for the presence of C(ampvlo- in any samples despite a mean serum level Efficacy of different dosage regimes in bacterpyloridis (CP) to determine the value of 4 95 mcg/mi (sd 0( 12). Peaik metronida- duodenal ulcer healing and eradication of of different tests in the diagnosis, using the zole levels in gaistric juice werc 61 [tg/ml (sd Campylobacter pylori bacteriological test as the gold standard. 8) at 3t) mins aind 30 tgr/ml (sd 0(23) in Twenty six unselected patients were serum at one hour. J (G (C(GiILAN. I) GIll(iAN, If iiUMPiiRYS. 1) studied. Five antral biopsy specimens were These findings suggest that gastric secre- MCKI-NNA. F SWEiENEY, C K-.ANI.. ANi) ( taken for culture and bacteriological tests. tion of antibiotics does not explain their O MoRAIN (Dept of Micro (111(d Histopath, SI histology (morphology and Warthy and varying efficacy in the eradication of C James( Hospital andit Trinity (ollege, Dept of' Starry (WS) staining), and urease test (120- pyloridis. Other factors, such as luminal Gastro, MetathiA dtelaide Hospitals, Dlblin, 18t) min and 24 h). Serum antibodies against effects of oral atntibiotics on gastric mucus Irelandti) C(ampvylobacter pYlori (CP) status sonicated CP organisms were assayed by an and mucosa. and tissue levels may be more of piatients with healed duodenali ulcers hias ELISA IgA, IgG. and IgM as well as an IgG important. recently been shown to be highly predictive immunoblotting technique (IgG-IB). ot the likelihood of relaipse. Colloidall Campylobacter pyloridis was found by bismuth subcitrate (CBS) is active against culture in 5°0% of the patients and fulfilled In vitro mucus glycoprotein synthesis and CP in vivo. The atim of this prospective the bacteriological criteria for CP. The WS secretion by gastric mucosa colonised with controlled triill was to assess the efficaicy of staining and IgG-IB gave a sensitivity of campylobacter pyloridis CBS 120 mg qds v 240 mg bd in ulcer healing 100)% and a specificity of 85%, ELISA-IgG and CP eradication. 85% and 91%/0, ELISA-IgA 46%Yo and 85%, J E CRABTRIE, B J RAlU'IBONI-., J WYA'T, R V Sixty consecutive piatients with endo- histological evidence of gastritis 92% and IIEATLEY, AND M S l.OSOWSKY (Dep)t of) scopic duodenal ulcers (DU) randomised 540%, urease test (120-180 min) 70% and Medicine and Dept of Pathologs, St James 's (30 bd 30 qds CBS). Repeait endoscopy was 100)/0, urease test (24 h) 92% and 54%° as to University Hospital, Leeds) There is a performed at four weeks and again at eight sensitivity and specificity, respectively. No strong correlation between Camp(yobhacter weeks in patients who haid not heilled at four IgM anti-CP were detected in serum. pyloridis colonisation and gastritis. The weeks. At each endoscopy two antral biop- The WS staining technique and IgG-IB association between surface C pyloridis sies were taken from <2 cm from the were the best techniques to detect the with depletion of neutral cytoplasmic pylorus and assessed histologically and presence of CP, followed by ELISA-IgG. mucins in the gastric epithelial cells raises microbiologically for evidence of CP. The urease test was less satisfactory. None the possibility that C pyloridis may be At entry 90%) of both groups were of the patients but one with normal histo- directly or indirectly affecting the protective positive for CP, at four weeks 62%' of bd logy had a positive culture. Three patients mucus layer in the stomach. To study the and 33%, of qds patients remained CP with chronic antrum gastritis had a negative capacity of normal and gastritic mucosa to positive (p<0-05), at eight weeks 50%, of bd culture and WS staining but positive anti- synthesise and secrete mucus glycoproteins, patients and 16% of qds patients remained bodies, thus suggesting, a possible aetio- 24 hour in vitro cultures of antral and body CP positive (p<0-02). http://gut.bmj.com/ logical role of CP in chronic antrum gastritis biopsies were undertaken. The incorpora- At the end of the study period there was in addition to the well established CP role in tion of "H glucosamine into tissue anid no significant difference in healing rates acute antrum gastritis. secreted glycoproteins was measured between the groups (65%, of bd and 75('o of (DPM x I 0/mg protein). qds having healed). C pyloridis colonised. antral biopsies Ods dosage reduces CP infection more secreted significantly higher quantities of effectively and should he associated with a Gastric secretion of antibiotics used for labelled glycoproteins than normal antral lower DU relapse rate. Different mecha- tissue. Mean values Campylobacter pyloridis respectively were nisms of action must operate in CP eradica- on September 26, 2021 by guest. Protected copyright. 106±14-2 (n=6) and 58-7±98- (n=7) tion and DU healing with CBS. J A iiOL,INGSWOR1Tii, J (GOiLDIE, C F SIllEi'll', Y (p<0(05). Conversely, tissue associated I,, H RICIIARDSON, AND R H HUNT (McMaster labelled glycoproteins were higher in University Medical Centre, Hamilton, normal antral biopsies (198± 19-2) than Ontario, Canada) Erythromycin has a low gastritic biopsies (159+ 15 5). Total Campylobacter pyloridis in tropical Africa rate of eradication of Campylobacter incorporation of glucosamine into tissue pyloridis (150%) while metronidazole and and secreted glycoproteins was significantly JUDITlI I WYATT, J S DE CAESTFCKER, B J ampicillin csters are highly effective (85%). greater (p<0.0l) in C pvloridis infected RAItIBONE, AND R V HIEATiLEY (Depts Patho- We have found C pyloridis difficult to body biopsies (258± 19 2; n=7) than normal logy and Medicine, St James's University eradicate from the gastric glands and postu- tissue (146±10(3; n=8). The increase in Hospital, Leeds and Dept Medicinte, late that while topically active agents may glycoprotein synthesis correlated with an University of Science and Technology, clear the organism initially early relapse increase in epithelial cell numbers (r=().66, Kumasi, Ghana) Virtually all Campylo- may be associated with persistance in gastric p<005). The ratios of tissue to secreted hacter pyloridis (CP) studies to date have pits. Gastric secretion of antibiotics should glycoproteins for normal and gastritic body concentrated on western style populations, result in high drug concentrations in the tissue were 2-8:1 and 17:1 respectively. yet in the tropics duodenal ulcers are gastric glands. Gastric juice levels of These results show that in non- reported to be particularly common and metronidazole and ampicillin were autoimmune gastritis where C pyloridis benign gastric ulcers rare. We studied the measured in four subjects in samples taken is present significant alterations to gastric presence of CP, its relation to mucosal one hour before and two hours after the mucus production occur. Whether the inflammation and patients serological drug were given intravenously. Ampicillin alterations in mucus production are a direct responses in 39 patients being endoscoped was measured by bioassay and metronida- affect of C pyloridis remains to be in Kumasi, Ghana, West Africa. Histology zole by HPLC. No ampicillin was detected determined. wals performed on antral, body, and duo- Gut: first published as 10.1136/gut.28.10.A1328 on 1 October 1987. Downloaded from A 1410 The British Society ofGastroenterology denal biopsies including a modified Giemsa Non-invasive measurement of gastric empty- of selected subjects without gastritis (men stain for identifying CP. Serum antibody ing using applied potential tomography 45, n=9, 55, nr=l10 women 45, n=-l, 55 titres to CP were studied by ELISA using a (APT) n=8) and plasmat gastrin concentrations soluble antigen preparation. The patients measured. In the retrospective samples, the mean age was 41 years (range 12-71) (male: I) F FVANS, J W WRl(IlG, (G LAMONT, AND J D only significant change was a rise in ECL female 28:1 1). The mean duration of iIARDCASTiLF (Department of Surgerv, cells of older females (13-6±1.9, mean+ abdominal symptoms was four years. Thirty University Hospital, Nottingham) Applied SEM, cells/visual field) compared with the eight of 39 patients had antral gastritis, and potential tomography is a new non-invasive young group ( t)-6+±0.8, p<0)-0)3). The pros- 23 of these (59%) had duodenal ulcer (14) technique which measures changes in tissue pectively biopsied, however, selected sub- or duodenitis (nine). The 38 gastritic resistivity via surface electrodes. Gastric jects of both sexes showed reduced ECL patients were all CP +ve, and the single emptying of meals can be assessed using this cells with age (mcales 45, 50)+ 106, 55, normal subject -ve. The prevalence of CP method without the need for radioisotopes 33+3-6. p<)-05:, females 45, 44±6o5, 55, colonisation in this African population is or expensive nuclear imaging equipment. 31+±44, p<0)05). Gastrin concentrations the highest reported in any study. The Five normal subjects were imaged on two did not change within sexes but were higher strong association with CP gastritis and occasions after ingestion of 500 ml Oxo in older females (229±+7-5 pmol/l) com- duodenal disease seen in the Ghana patients drink and again after 500 ml of Quaker Oats pared with older men (63+±0-6, p<0O05). is similar to that observed in the UK. porridge to assess liquid and solid emptying. The difference in the two sets of results may Resistive images were collected at one reflect the high incidence of gastritis minute intervals for 60 and 180 minutes observed in non-selected older women. respectively. The tests were repeated after This in turn may relate to plasma gastrin The effect of vagotomy on Campylobacter 40t) mg of cimetidine as gastric acid secre- concentrations which were relatively high pylori tion is thought to influence imaging using even in the selected group of older females. APT. These variations should be taken into BELINDA J JOHNSTON, P I REED, AND M H Al.I The time taken to empty 5000 of the test account when assessing pathological (Departments of Gastroenterology and meals was expressed as ti,. In the control changes in ECL cells. Histopathology, Wexham Park Hospital, studies ti, for the liquid meal was a median Slough, Berkshire) It is recognised that the of 35 min (range 20-40 min) compared with gastritis seen in duodenal ulcer (DU) ti, of 19 min (range 18-31 min) with cimeti- patients is associated with the presence of dine (p=)-028). For the solid meal ti, con- Duodenal acidification and gastrin responses antral Campylobacter pylori (CP). It has trol was a median of 102 min (range 80-117 after feeding: a new look at the patho- been suggested that after gastric surgery the min) compared with tin 68 min (range 43-94 physiology gastritis type will alter and may no longer be min) with cimetidine (p=0016). associated with CP presence. Applied potential tomography is a uscful C A ERIKSEN, K D BUCHIANAN, AND A CUSCIIFERI http://gut.bmj.com/ To establish the existence of such a differ- technique to evaluate gastric emptying and (Department ofSurgery, Ninewells Hospital ence, gastric antral biopsies were taken is particularly suitable when multiple and Medical School, Duniidee and Dept of from 61 patients who underwent vagotomy investigations are required. Cimetidine Medicine, Queen 's University (f' Belfast, for DU, 1-20 years previously, and from 75 does modify the emptying pattern and this Belfast) Controversy exists regarding untreated patients with active DU. Of those should be considered for future studies. the duodenal acidification and gastrin who had surgery 27 had highly selective responses to sham feeding and a meal in vagotomy (HSV), 26 vagotomy and pyloro- ulcer disease. We measured plasma gastrin plasty (VP) and eight truncal vagotomy and and duodenal bulb pH before, during, and on September 26, 2021 by guest. Protected copyright. gastroenterostomy (TVGE). The biopsies Enterochromaffin like (ECL) cell popu- after modified sham feeding (MSF) and a were assessed histologically and examined lations are dependent on age and sex solid meal in 16 duodenal ulcer patients for the presence of CP. Gastric juice pH was (DU) and 12 volunteers (VOL). Gastrin measured in the vagotomy patients. A E BISHOP, D M GRFENiG RINDI, F I l.EE, P J levels were significantly higher in DU Campylobacter pylori were present in 72 ISAACS, M J DALY, J DOMIN, S R BliOOM, ANI) J M (fasting: DU 42 5 ng/l, VOL 22-5 ng/l, (96%) of the DU patients all of whom had POLAK (Depts of Histochemistrv and p<0)-001; meal peak: 130)(, 60-0, p<0(02). histological gastritis. Forty four (71%) of Medicine, RPMS, Hammersmith Hospital, Two distinct DU groups emerged: 'hyper- the vagotomy patients were CP positive and London, Dept of Pathology, Leeds General gastrinaemic' (HrG) showed exaggerated 41 of these had histological gastritis (HSV Infirmary, Leeds, Dept of Gastroenter- gastrin responses; 'normogastrinaemic 67%, VP 65%, and TVGE 75/), which ology, Victoria Hospital, Blackpool, and (N"G) showed levels similar to controls. tended to be more pronounced in the Astra Pharmaceuticals, Edinburgh) To Cephalic stimulation produced significantly TVGE group. The severity of the gastritis examine variations in ECL cells with age greater responses only in H'G (HiG fasting was unrelated to the intragastric pH or time and sex, a two part, retrospective and 67-7 ng/l, MSF peak 13t)() ng/l, p The British Society of Gastroenterology A 141 1 These results show a hypergastrinaemic' The aim of this study was to standardise the p<)-t)5, n=3). Antral luminal pH was subset of DU patients. exhibiting marked definition of the antrum in terms of the significatntly raised alt 24 hours (3-35±t)-59 cephalic responses, abnormal duodenal macrocopic antrum - corpus boundary compared with l-81±t)15. p<)')2, n=6) cidification and a defective switch off defined by the nerve of Latarjet (NL-ACB) returning to normal by day 28. mechanism of acid secretion. and microscopic ACB according to both Indomethiacin damages mucosa without parietal cells (PC) and gastrin cells (GC), altering intramucus pH aind there is evid- and hence determine if HSV provides ence of mucosal adaptation with continued Evidence for a gastro-cholecystic reflex for reliable denervation of the distal PC mass. administration. gall bladder emptying in man Serial sections obtained from longitu- dinal strips of 43 human 'normial' post- S E'LLENBOGEN, J S GRIME, J CAIAM, C R mortem stomachs were stained for PC (43 Acidification of the perfused human stomach MACKIE, S A JENKINS, AND J N BAXTI.R stomachs) and GC (in 20 of the 43). The PC- during muscarinic-M l-receptor blockade (Department of Surgerv, University of ACB was distal to NL by more than I cm in stimulates gastric prostaglandin (PG) E2 Liverpool, Department Of Nuclear 26 stomachs (61'%). In seven stonmachs output Medicinie, Royal Liverpool Hospital, (16'%) PC extended to the pylorus ('acid Of 2t) stomachs for Department of Gastroenterology Roval PG antra'). the stained GC A MiERTI-NIEIiSEN, 1 K MUNCK, K BUKIIAVI, Med School, Lonidoni) A gastric phase of and PC. PC extended to the pylorus in four AND J RASK-MADSI N (Departmlnens oJ gall bladder emptying (GBE) has been (20o). In these, GC were sparse and the Medical Gastroenterology, Bispebjerg and demonstrated in the dog. In this study "Tc'- antrum as defined by GC was smaller Herlevy Hospitals, University oJ' Deintark) EHIDA cholescintigraphy was used to con- (p<0)-01). The GC-ACB correlated much Pirenzepine dose-dependently increases better with NL-ACB than did PC-ACB. firm its presence and mechanism ot action in duodenal HCO 3 secretion, in addition to man. Healthy volunteers were studied; These findings suggest that current tech- inhibiting gastric H' secretion. Further- group 1, no gastric distension (n= 18); group niques of HSV often do not provide reliable more, duodenal aicidification stimulates 11, gastric distension by balloon (n =9); PC denervation, particularly in patients HCO A and PGE, output. To study the group 111, atropine given before gastric with 'acid antra'. T'hese patients may be influence of gastric luminal acidification on distension (n=7); group IV, meal ingestion identified by preoperative histological muscairinic regulation of gastric PG release (n= 14). Gastric distension was also per- examination of antral biopsies or peropera- 'steady state' perfusions of the stomnach formed in patients with truncal vagotomy tive Grassi test. were carried out in eight healthy volunteers group V (n=9). Blood samples were taken during 'shamteeding' before and after oral for cholecystokinin bioassay. In group 1, the administration of pirenzepine (5t) mg bid; probability of spontaneous GBE in any Effect of indomethacin on human gastro- four days). Luminal acidification (30) mM minute period was 0(0053. Significant GBE barrier HCI) slightly decreased gastric peak acid duodenal 'mucus-bicarbonate' http://gut.bmj.com/ occurred in six of nine (66%0) group 11 output (PAO) (1-+(0-5 v control 2-6±t)3 (p<0.00(l, group II v group 1, Poisson Test), C J SHJORROCK AND W D W REES (Hope mmol/15 min; mean+SEM; p A 1412 The British Society of Gastroenterology Reproductive Biology, Edinbt,rgh) The metabolite ot PGE - 13,14-dihydro 15-keto randomised into one of four groups (1) No incidence and virulence of peptic ulcer PGE, in gastric juice increased from GB, No D (n-4); (2) GB, No D (n=4); (3) disease has fallen in the Western hemis- 192±19 (SEM) to 1335 (+708) ng/h after No GB, D (n=3); (4) GB, D (n=5) aind phere, as consumption of polyunsaturated LA (p<0(01). These data suggest an havc completed a three month trcatment fatty acids has increased. We havc explanation for the observed relationship period. All patients had endoscopy with examined the effects of dietary poly- between dietary polyunsaturated fatty acid real or sham GB insertion. Three month unsaturated fat on gastric atcid secretion, intake and peptic ulcer disease; poly- weight loss (kg): (1) -)-9±+13, (2) prostaglandin output and serum gastrin unsaturated fatty acid ingestion modifies -0)-9± 13, (3) -5-9±3+1, (4) -11-3± 1*3; concentration. Nine healthy volunteers gastric prostaglandin metabolism with p<0-05 for variation among the mean took 1-5 g or 3 g of linoleic acid (LA) for secondary changes in acid secretion and weight losses and for I v 4 and 2 l} 4. Liquid 14-21 days. Linoleic acid did not affect gastrin output. GE wais significantly more rapid two wceks gastroduodenoscopic appearances, gastro- after GB insertion as compared to pre-GB: duodenal histology, routine h(aemratology ti,: 11±2 v 19±3 min; time to duodenal nor serum and urinary biochemistry. Four visualisation: 3± 1 v 7± 1 min; {MO residual at subjects developed mild diarrhoea. Mean 3(0 min: 17±2 l 32±5%/O. A significant basal gastric acid output was 8-3±1-5 A prospective, controlled trial of the garren correlation wis seen between weight loss (SEM) mmol/h before LA and 7-2±1-3 gastric bubble (GB) with or without 600 and the ti, for liquids after GB insertion (SEM) mmol/h after LA (p>0(05). Mean calorie diet (D) on weight loss and gastric (r=(182, p-(0007). Although aIn erratic pentagastrin stimulated gastric acid output emptying (GE) solid GE curve developed aftcr GB inser- decreased from 35-2±3-5 to 30-1 ±2-8 tion, quantitative pairiameters of solid GE mmol/h (p<0-05). There was a correspond- N (GEMAYIE, I.AINI., 11 COHIEN, N ARNSIEIN, were not significantly difterent. ing increase in mean serum gastrin concen- AND M BOOSAI IS (INTRoDuCrE BY J Interval results of this ongoing trial tration from 19 22±3-7 to 30-89±3-8 pg/mI VALEN/ZULLA) (USC Schiool of Medicine, suggest ( I ) dietary instruction is the key (p<0-0l). The mean output of immuno- Los Atigeles, C(A, USA) Controversy exists factor in this weight loss prograrm, (2) GB reactive PGE in gastric juice increased from regarding the efficaicy and physiologic without dietary therapy is ineftective, and 498±110 (SEM) ng/h to 123(0±475 ng/h effects of the GB. Sixteen obese women (3) liquid GE is significantly haistened aifter (p<0-05). The mean output of the main (age 3(0-58, BMI 32-52 kg/m') have been GB insertion. http://gut.bmj.com/ on September 26, 2021 by guest. Protected copyright.