Showing papers in "Gut in 1976"

Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis.

Abstract: The frequency of HLA-A3 and HLA-B14 antigens was significantly higher in a series of 51 patients with idiopathic haemochromatosis than in a control group, being respectively 78-4 versus 27-0% and 25-5 versus 3-4%. This finding strongly supports the suggestion that idiopathic haemochromatosis is a genetic disease and suggests that the gene(s) responsible for the disease may be linked to the histocompatibility genes.

Distribution and release of human pancreatic polypeptide.

Abstract: A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours.

Measurement of the mean transit time of dietary residue through the human gut.

Abstract: A new method is described for measuring the mean transit time (MTT) of digesta through the human gut in which a constant amount of marker (radio-opaque pellets) is fed to subjects with each meal over a period of weeks, and its excretion measured in the stools. The MTT measured by this method (MTT-C) has been compared with MTT measured by giving single doses of similar markers to the same subjects (MTT-S) and with the 80% transit time (80% TT). Mean values on three dietary regimes for the MTT-C (54.2 h +/- 2.5) and MTT-S (54.2 +/- 2.6) were lower than that for 80% TT (63.1 +/- 3.0). The average MTT-C in a group of six healthy young men on an ad libitum diet was 2-3 days (range 0-7-4-0). When additional dietary fibre was added to a standard diet the average MTT-C fell (in all of five subjects) from 2-4 to 1-6 days. A continuous record of MTT-C is obtained by this new method which shows wide variations from week to week even on controlled dietary intakes. Using the single dose technique, evidence is produced which suggests that the MTT-S is a more accurate and reproducible method than the 80% TT.

Coeliac disease, gluten-free diet, and malignancy.

Abstract: Two hundred and two patients with coeliac disease or idiopathic steatorrhoea previously reported from this unit have been reviewed after a further 10 years of follow-up. Of 20 more deaths, 10 were due to malignancy. A separate study was made of all patients with histologically confirmed coeliac disease seen to the end of 1972 and followed up to the end of 1974. Twenty-one of the 43 deaths in this series were due to malignant tumours, of which 13 were reticulum cell sarcomas. There was no evidence that patients showing sub-optimal clinical response to gluten withdrawal or persisting falt jejunal biopsies were more prone to die of cancer. A gluten-free diet did not appear to be effective in preventing malignant complications, but a longer follow-up of patients will be necessary to provide a final answer to this question.

Influence of autonomic nerves on the internal and sphincter in man.

Abstract: The internal and sphincter receives its parasympathetic nerve supply from the sacral outflow and its sympathetic supply from the thoracicolumbar outflow of the spinal cord. In order to investigate the influence of the tonic discharge of these nerves, eight healthy subjects receiving high spinal anaesthesia (T 6-T 12) and five receiving low spinal anaesthesia (L 5-S 1) were examined. Continuous recordings of anal pressure and electromyographic activity from the external sphincter were obtained during rest and during expansion of the ampulla recti by means of an air-filled balloon. The results were compared with those obtained in an earlier study from 10 subjects with a bilateral pudendal block which paralysed the striated sphincter muscles without affecting the autonomic nerve supply to the internal sphincter. Anal pressure at rest decreased significantly more with high spinal anaesthesia (32 +/- 3-2 mm Hg) than with low (11 +/- 7-1 mm Hg) or with pudendal block (10 +/- 3-9 mm Hg) and the relaxations of the internal sphincter induced by rectal distension were somewhat smaller with high spinal anaesthesia. However, the remaining anal pressure at maximal relaxation, induced by a substantial rectal distension, was essentially the same with the three forms of anaesthesia. It is concluded that, at rest, there is a tonic excitatory sympathetic discharge to the internal anal sphincter in man. However, this seems to be without excitatory effect when the sphincter is relaxed after a substantial rectal distension. Furthermore, the results indicate that at rest there is no tonic parasympathetic discharge affecting the sphincter tone.

Exocrine pancreatic function in juvenile-onset diabetes mellitus.

Abstract: Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.

Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis.

Abstract: Samples of serum, bile, and urine were collected simultaneously from patients with cholestasis of varying aetiology and from patients with cirrhosis; their bile acid composition was determined by gas/liquid chromatography and mass spectrometry. In cholestasis, the patterns in all three body fluids differed consistently and strikingly. In serum, cholic acid was the major bile acid and most bile acids (greater than 93%) were unsulphated, whereas, in urine, chenodeoxycholic was the major bile acid, and the majority of bile acids (greater than 60%) were sulphated. Secondary bile acids were virtually absent in bile, serum, and urine. The total amount of bile acids excreted for 24 hours correlated highly with the concentration of serum bile acids; in patients with complete obstruction, urinary excretion averaged 71-6 mg/24 h. In cirrhotic patients, serum bile acids were less raised, and chenodeoxycholic acid was the predominant acid. In healthy controls, serum bile acids were consistently richer in chenodeoxycholic acid than biliary bile acids, and no bile acids were present in urine. No unusual monohydroxy bile acids were present in patients with primary biliary cirrhosis, but, in several patients, there was a considerable amount of hyocholic acid present in the urinary bile acids. The analyses of individual bile acids in serum and urine did not appear to provide helpful information in the differential diagnosis of cholestasis. Thus, in cholestasis, conjugation of chenodeoxycholic acid with sulphate becomes a major biochemical pathway, urine becomes a major route of bile acid excretion, and abnormal bile acids are formed.

Course and prognosis of Crohn's disease.

Abstract: During the period 1938-70 there were 303 patients at the Radcliffe Infirmary, Oxford, diagnosed as suffering from Crohn's disease. Of these, 82 have been excluded, leaving 221 with a firm diagnosis. These patients have been divided into 'new cases', in which the disease was diagnosed at the Radcliffe Infirmary, and 'referred cases' in which the diagnosis was already made at the time of referral. In this series, there were three main sites of involvement: small intestinal, large intestinal, and both small and large intestinal. Ileocolitis was the commonest anatomical distribution. The disease showed progression to new, sites in a considerable number of the patients during the period under study. There was a fivefold increase of new cases between the first and third decades covered by the study and this applied equally to patients presenting as an acute abdomen, which supports the idea that the disease is truly increasing. Survival curves have been plotted and compared with expected survival curves. In terms of mortality, Crohn's disease emerges as a disease which becomes progressively more dangerous as the years go by, which is in sharp contrast with the findings in ulcerative colitis in which the main risk of dying is in the early years.

Patchiness and duodenal-jejunal variation of the mucosal abnormality in coeliac disease and dermatitis herpetiformis.

Abstract: The incidence and degree of patchiness of mucosal abnormality in both coeliac disease (CD) and dermatitis herpetiformis (DH) is documented. As judged by both stereomicroscopy and subjective histology, patchiness occurred frequently in both CDand DH patients. In most cases the difference of abnormality was of only one grade, but in approximately 25% as assessed by stereomicroscopy and 10% as assessed by histology the difference was of two or more grades. In control subjects with normal small bowel mucosa the variation of the mucosal appearance between the duodenum and proximal jejunum was studied. Contrary to popular belief, no significant difference of villous and crypt measurements or of apparent villous "bridging" and "branching" between these two sites was found, if only well-orientated sections were studied. The stereomicroscopic appearances were also similar at these two sites, although villi tended to be broader in the duodenal biopsies. The duodenal-jejunal variation was also studied in CD and DH patients and although by both stereomicroscopy and subjective histology the appearances were similar in most patients, in approximately 33% the duodenal abnormality was the most severe and, surprisingly, the jejunal abnormality was more severe in approximately 15%. It is concluded that multiple, precisely located biopsies of both the duodenum and proximal jejunum are invaluable in the investigation of small bowel disease and in assessing response to treatment.

Idiopathic bile acid catharsis.

Abstract: In the course of extensive routine screening for bile acid malabsorption a few patients were detected in whom chronic diarrhoea was apparently induced by excess bile acid loss which was neither associated with demonstrable conventional ileopathy nor with any other disorder allied to diarrhoea. In three patients subjected to scrutiny the results obtained were in harmony with a concept of idiopathic bile acid catharsis. Ingestion of cholestyramine was followed by immediate relief, but the diarrhoea recurred whenever this treatment was withdrawn. It it suggested that idiopathic bile acid catharsis should be suspected in patients with unexplained chronic diarrhoea and especially in those with a diagnosis of irritable colon with diarrhoea.

Intravenous administration of diazepam in patients with chronic liver disease.

Abstract: The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...

Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis BS antigen.

Abstract: To determine the clinical implications of HBSAg in severe chronic active liver disease (CALD), patients with HBSAg positive CALD were compared with those chosen by identical clinical, functional, and morphological criteria in whom this test and anti-HBS were negative. HBSAg positive patients were predominantly males over 40 years of age and more frequently failed to respond to conventional treatment programmes with prednisone. HBSAg negative patients were more often female and younger, had a higher incidence of associated immunopathic disease and immunoserological markers in high titre, and more often responded to treatment with full remission of their disease. HBSAg positive patients failing treatment with conventional doses of prednisone often improved with higher doses, but did not reach full remission of their disease. The benefit-risk ratio of both conventional and high doses of prednisone in HBSAg positive severe CALD needs further clarification.

Transit through the gut measured by analysis of a single stool.

Abstract: A method is described for measuring transit time through the gut which requires the collection of only one stool. A dose of 20 radio-opaque markers is given to the subject on each of three consecutive days with breakfast, each dose of marker being of a different type. The first stool passed after rising on the fourth day is collected and its marker content analysed. The method has been validated in 15 subjects by comparing it on 36 occasions with mean transit time measured by a continuous marker technique (MTT-C). In 35 of these studies transit measured from a single stool (SST) and MTT-C were significantly correlated R = 0.78 P less than 0.001. In one study the designated stool contained none of the SST markers. An alternative way of validating the SST method is described by comparing it with the average of the three mean transit times from three separate doses of marker (MTT-S). The average MTT-S agreed very closely with MTT-C in 36 studies R = 0.94 P less than 0.001 and proved a satisfactory alternative method for validating transit techniques. In a total of 66 studies in 22 subjects average MTT-S correlated significantly with SST, R = 0.85 P less than 0.001.

Effect of cimetidine on 24-hour intragastric acidity in normal subjects.

Abstract: The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals.

Measurement of anal pressure and motility.

Abstract: A fine open perfused system and a closed balloon system for the measurement of anal pressure and motility have been compared. Measurements were made in 40 normal subjects and 84 patients with haemorrhoids. The rate of perfusion had a marked effect on the recorded pressure and motility details. The motility pattern was seen most clearly with the balloon probe and the pressure recorded was reproducible and easy to measure, making this a convenient method for recording activity of the internal anal sphincter. Anal motility in normal subjects was characterised by slow pressure waves (10-20/min). The frequency was fastest in the distal anal canal and this frequency gradient may represent a normal mechanism to keep the anal canal empty. Ultra slow pressure waves (0-6-1-9/min) were seen in 42% of patients with haemorrhoids and 5% of normal subjects and arose from a synchronous contraction of the whole internal sphincter.

Mucosal gastrin concentration, molecular forms of gastrin, number and ultrastructure of G-cells in patients with duodenal ulcer.

Abstract: The mean antral immunoreactive gastrin (IRG) concentration of 38 duodenal ulcer (DU) patients was significantly higher (35-9+/-5-2 mug/g) than that of 21 controls (15-9+/-2-6 mug/g). Also the mean IRG concentration in the proximal duodenal mucosa of 15 DU patients (3-2+/-0-8 mug/g) was higher (but not significantly) than that of 10 controls (1-8+/-0-5 mug/g). The number of G-cells in the antral mucosa of 58 DU patients and in the duodenal mucosa of 29 DU patients was not larger than that of controls. The distribution of immunoreactivity in gastrin components has been investigated in the antral and duodenal mucosa of six DU patients and six controls. In the antral mucosa the mean percentage of G-17 was 93-3% in DU patients and 92-0% in controls. G-34 amounted to 4-0% in DU patients and to 5-0% in controls. The G-34 percentage in the duodenal mucosa was higher (however not significantly) in the DU patients than in the controls (50-1% versus 35-8%). Ultrastructurally, the antral G-cells of DU patients had a significantly lower density index of their secretory granules suggesting higher functional activity. It is concluded that the exaggerated serum IRG response of DU patients to different stimuli is not a consequence of an increased G-cell mass.

Oral administration of a chymotrypsin-labile peptide--a new test of exocrine pancreatic function in man (PFT)

Abstract: One gram N-benzoyl-L-tyrosyl PABA was orally administered to 24 controls, 15 patients with chronic exocrine pancreatic disease, 13 patients after an attack of acute pancreatitis, two patients with gluten-sensitive enteropathy, and 10 patients with biliary tract disease, peptic ulcer, or other pathology of the gastrointestinal tract. In the presence of chymotrypsin, PABA is split from the peptide and excreted in the urine. The amount of PABA excreted serves as a parameter of exocrine pancreatic function. In 51 patients, exocrine pancreatic secretion was also assessed by the Lundh test. In the control group a mean of 59-6 +/- 12-2% (mean +/- 2 SD) of the peptide-PABA was excreted over a period of six hours. PABA excretion in exocrine pancreatic deficiency was significantly less (P less than 0.001) than in controls. With one exception no overlap of data was noted. In the group with exocrine pancreatic deficiency, a significant relationship was shown between the PFT and the Lundh test. Reproducibility in duplicate test was excellent. The present data justify further investigations of this procedure as a possible new oral test of exocrine pancreatic function.

Fibreoptic endoscopy and the use of the Sengstaken tube in acute gastrointestinal haemorrhage in patients with portal hypertension and varices.

Abstract: The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.

Hepatitis B antigen (HBSAg) and/or antibodies (anti-HBS and anti-HBC) in fulminant hepatitis: pathogenic and prognostic significance.

Abstract: Hepatitis B surface antigen (HBSAg) and antibodies to both the surface and core antigens of the hepatitis B virus (anti-HBS and anti-HBC) have been studied in 64 consecutive cases of fulminant hepatitis. HBSAg was detected by counterelectrophoresis in 23 (35-9%) but by radioimmunoassay in 38 (59-3%). Anti-HBS was detected by passive haemagglutination in 26 (40-6%), coexisting HBSAg and anti-HBS were found in 16 cases (25%). Using an indirect immunofluorescence technique, anti-HBC was found in all of the cases in whom either HBSAg or anti-HBS was present. The highest survival rate was observed in patients with no evidence of HBV infection (31-3%) and was lowest in those who had both HBSAg and anti-HBS detected simultaneously (6-2%). The prognosis of those who exhibited anti-HBS only was no better than those with HBSAg alone. In a further case, transient interruption of the asymptomatic chronic HBSAg carrier state with seroconversion to anti-HBS was associated with the development of a fulminant hepatitis syndrome. The results suggest that an unusually strong and rapid immune clearance of HBSAg may be involved in the pathogenesis of fulminant hepatitis.

Tranexamic acid and upper gastrointestinal haemorrhage--a double-blind trial.

Abstract: The efficacy of antifibrinolytic therapy in the management of acute upper gastrointestinal haemorrhage has been investigated in a double-blind clinical trial. Two-hundred patients were studied using tranexamic acid, a potent antifibrinolytic agent. Of these, 103 were in the treatment group and 97 in the control group. Patients were analysed to determine severity of initial blood loss, transfusion requirements, together with the incidence of recurrent bleeding, surgical intervention, and death. Final diagnosis as to the site of bleeding was arrived at using endoscopy, barium studies, and the findings at operation and necropsy. The groups were well matched as regards severity of initial haemorrhage, age, sex, aetiological diagnosis, and precipitating factors. A significant difference was observed in the requirement for surgical intervention to control continuing or recurrent haemorrhage. Twenty-three of 97 in the control group and seven of 103 in the treatment group required surgery. There appeared to be a reduction in the transfusion rate after the first three days of hospitalization in the treatment group. There were no significant differences in mortality or in side-effects between the two groups.

Progress report. Familial inflammatory bowel disease--heredity or environment?

Abstract: Soon after ulcerative colitis was first recognized as a disease entity distinct from epidemic dysentery, occasional instances of familial cases were reported but, early in the twentieth century, these were regarded as being merely coincidental'. Some years later, the man in whom Crohn made his initial observations of ileitis was found to have a sister similarly affected and Crohn suggested the name 'familial ileitis' for the condition2. It has become generally accepted that both of these inflammatory bowel diseases (IBD) are sometimes familial. When this subject was reviewed in the first volume of Gut3 the significance of familial cases was uncertain. Despite advances in the intervening years the cause, or causes, of IBD remains unknown4, and the significance of familial involvement is still conjectural.

Galactose elimination capacity as a prognostic index in patients with fulminant liver failure.

Abstract: In 25 patients with fulminant hepatic failure the prognostic value of a quantitative liver function test, the galactose elimination capacity, was assessed and comapred with routine liver function tests and clinical features. The galactose elimination capacity was significantly higher (P less than 0-05) in the five patients who survived than in the 20 patients who died. None of the other liver function tests, was significantly different. The values of the galactose elimination capacity overlapped considerably between survivors and non-survivors, but all patients with a galactose elimination capacity below 12-8 mumol galactose/min and kg body weight died. The disease among most patients who died having a galactose elimination capacity greater than 13 mumol ran a subacute course. It is suggested that quantitative liver function tests be included when new treatments of fulminant hepatic failure are investigated.

Inhibition of food-stimulated gastric acid secretion by cimetidine.

Abstract: The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed.

Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease.

Abstract: Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients.

Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27).

Abstract: Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease.

Antibiotics in biliary disease: the relative importance of antibiotic concentrations in the bile and serum.

Abstract: A randomised controlled trial has been performed in 150 patients undergoing biliary operations to determine whether an antibiotic which is excreted almost entirely in bile (rifamide) is to be preferred to one having satisfactory serum levels only (gentamicin). Patients were allocated to one of three groups: 50 received gentamicin, 50 received rifamide, and there were 50 controls who received no antibiotic cover. In the absence of duct obstruction, rifamide achieved extremely high bile levels but low serum concentrations. However, in jaundiced patients, both the bile and the serum concentrations of rifamide were too low to be of therapeutic value. The incidence of postoperative sepsis was not reduced by rifamide compared with controls. In contrast, gentamicin achieved adequate serum concentrations in 88% of patients. Despire poor bile levels, gentamicin was associated with a significant reduction of wound infection from 22% to 6% and septicaemia from 14% to 2% compared with controls. To reduce the septic complications of biliary operations, adequate serum levels of an effective antimicrobial are more important than an antibiotic, which is excreted almost entirely into the bile.

Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis.

Abstract: Bile acid loss (mg/m2 24h) in the stools of 43 cystic fibrosis (CF) children with pancreatic insufficiency was 751-1 +/- 48-3, while that of six without clinical evidence of pancreatic disease (133-4 +/- 15-9) did not differ from values in 25 controls (109-8 +/- 9-8). There was a good correlation between the degree of bile acid (BA) and fat sequestration. Concomitant changes in bile acid and fat loss were observed in the one group of six patients studied on and off pancreatic enzymes as well as in a second group of seven children treated with pancreatic supplements and maintained on a normal diet followed by a low fat diet supplemented with medium chain triglycerides. Administration of NA bicarbonate led to a significant decrease in fat loss (15-8 +/- 2-7 leads to 10-3 +/- 1-9) without any simultaneous change in bile acid excretion (533-1 +/- 58-3 leads to 500-4 +/- 58-6). Qualitative bile acid patterns in controls, in infants after an ileal resection, and in patients with CF or with coeliac disease showed that the percentage of primary BA followed closely the total amount excreted except in situations where antibiotics were administered. The exact mechanism for the increased loss of BA in CF is unknown. It is found in all age groups and is related to the presence and degree of pancreatic insufficiency. The possibility that unhydrolysed triglycerides may interfere with the intestinal absorption of bile acid needs further confirmation.

Lithocholate metabolism during chemotherapy for gallstone dissolution. 2. Absorption and sulphation.

Abstract: The amount of lithocholate input and the size of the total lithocholate exchangeable pool were measured using isotope dilution in three patients ingesting chenodeoxycholic acid for gallstone dissolution and two healthy control subjects. Because the specific activity decay curve was biexponential in appearance, input was calculated using a stochastic analysis employing the Stewart-Hamilton equation. By this method, the lithocholate input and the size of the exchangeable pool in gallstone patients during chenic acid ingestion was four to five times that observed in the healthy control subjects. It was calculated that about one-fifth of the newly formed lithocholate was absorbed in both gallstone patients and healthy control subjects. The extent of sulphation of absorbed lithocholate was then measured in seven gallstone patients whto had been ingesting chenodeoxycholic acid for gallstone dissolution by defining the chemical form of radioactivity in bile after intravenous administration of labelled lithocholate. Similar studies were carried out in eight healthy control subjects, but, in addition the extent of sulphation of injected lithocholylglycine and lithocholyltaurine was also defined. When lithocholate was injected, the majority of radioactivity in bile (50-60%) was present as sulphated conjugates, both in gallstone patients and healthy control subjects. The degree of sulphation was greater for glycine than taurine conjugates, and these findings, which suggested preferential sulphation of the glycine conjugates of lithocholate, were confirmed by showing that injected lithocholylglycine was sulphated to a much greater extent than injected lithocholyltaurine. These findings indicate that in patients receiving chenic acid there is effective sulphation of lithocholate, especially its glycine conjugates, despite a considerable increase in lithocholate absorption; they may provide an explanation for the lack of hepatotoxicity of chenic acid in man.

Demonstration of an intracellular copper-binding protein by orcein staining in long-standing cholestatic liver diseases.

Abstract: Liver biopsies from eight patients with primary biliary cirrhosis, two with chronic active hepatitis of a cholestatic form, three with long-standing alcoholic liver cirrhosis, and one with extrahepatic biliary obstruction were studied. In each case dark brown cytoplasmic material was seen after staining of the tissue sections with Shikata's orcein method. In exactly the same cellular and subcellular locations as the orcein-positive material, and with morphologically equal granules, two different ordinary staining methods for copper (rubeanic acid and Mallory-Parker's haematoxylin) gave positive reactions. The earlier histochemical findings have revealed the protein nature and high sulphydryl content of the orcein-positive material. Its close association with copper in liver sections suggests its copper-binding nature and indicates that a common copper-protein complex accumulates in the cytoplasm of liver cells during longstanding cholestasis in biliary diseases of various pathogenetic origin.

Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects.

Abstract: Bile acid composition was determined in duodenal and jejunal aspirates obtained under fasting conditions in normolipidaemic controls and in patients with the type IIa and type IV lipoprotein patterns. In 17 out of the 22 subjects studied, the duodenal as compared with the jejunal aspirates contained proportionally more CD (chenodeoxycholic acid) than C (cholic acid). The two types of aspirates also differed slightly with regard to the D (deoxycholic acid): CD ratio, which was higher in samples drawn from the jejunum. These findings, compatible with an absorpiton of about 30% of CD in the upper small intestine, were approximately the same in all groups of patients. As evidenced by additional experiments in two subjects, an oral intake of cream does not significantly influence the absorption of CD in the upper small intestine.