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Comparison of the iron binding capacity of gastric secretion under basal and histamine stimulated conditions showed no significant variation. However, following ‘flushing’ of the gastric mucosa the capacity to bind iron was approximately doubled. Since this procedure is known to cause increased mucus secretion it seems likely that the iron binding capacity in gastric juice is either of mucoid origin or associated with mucus secretion. From what is known of the properties of gastric iron binding the former seems to be the more likely. Furthermore since there is no evidence that iron binding in gastric juice is due to a single component it seems more appropriate to refer to ‘the iron binding capacity’ of gastric juice than to imply by the use of the name ‘Gastroferrin’ that a single entity is involved.

Martin(1) has shown that if the pressure p and the Lagrange variable ψ (ψ = constant on a trajectory) are taken as independent variables, then problems in one-dimensional unsteady flow of an ideal gas reduce to the question of finding solutions of the Monge-Ampère equationwhere τ = 1/ρ, ρ being the density, and S = S(ψ) is the specific entropy. Thus the right-hand term is a function of p and ψ depending upon the equation of state and the function S(ψ).

Evidence is presented which indicates that duodenal juice contains a component of high molecular weight which renders intrinsic factor incapable of binding vitamin B12. The extraordinary heat stability of this component suggests that it is not an enzyme. The degree of inhibition varies with different duodenal juices and is dependent upon the concentration of duodenal juice, the temperature, and the length of incubation. Total inhibition of posthistamine gastric juice intrinsic factor can be generally achieved by incubation with an equal volume of undiluted duodenal juice for 2 hr at body temperature. The inhibitory component acts on intrinsic factor rather than by competition with intrinsic factor for available vitamin B12.

Conditions are examined under which plane shook waves of constant strength can propagate through a gas in a given homentropic motion. Since the entropy change across the shock is taken to be constant homentropic flow exists behind the shock also. The motion behind the shock is determined by solving a Cauchy problem with data given on the back of the shock. The theory is illustrated by two examples, one of which generalizes a result obtained by Copson.

1. Three hundred and fifteen patients seen at 0-15 years after a gastric operation for peptic ulcer had an incidence of anaemia of 44% among the men and 34% among the women. 2. The mean haemoglobin level was shown to fall progressively and significantly with years after partial gastrectomy. This was most marked following the Polya gastrectomy and in pre-menopausal as opposed to post-menopausal women. 3. The gastro-enterostomy group, although showing no progressive fall in the mean haemoglobin, showed a significantly higher incidence of anaemia than the medically treated peptic ulcer group. This was probably due to the higher incidence of gastro-intestinal haemorrhage occurring in this group as compared with the partial gastrectomy group. 4. The medically treated peptic ulcer group showed a significant rise in the mean haemoglobin level with years after hospital treatment. Pre-operative anaemia was a highly significant factor in the incidence of anaemia following operation. The significance of this is discussed. 5. Haematological evidence of iron deficiency was found in 22.2% of these cases. The incidence was highest following the Polya gastrectomy and in women. 6. Megaloblastic anaemia was found in 3 cases (1.2%) in all of whom it occurred following a Polya gastrectomy. Two of these cases also had subacute combined degeneration.

Serial measurements in alcoholic subjects showed a profound fall of serum iron for three days after withdrawal of alcohol and a reversion of abnormal accumulation of erythroblastic haemosiderin to normal. These findings suggest an interference in normal haem synthesis, most probably by a direct effect.

LACTASE deficiency in a group of 33 post partial gastrectomy subjects was found to be no more common than in 16 normal control subjects. These results are similar to the reported results in the literature for Caucasian subjects and do not support the thesis that post gastrectomy milk intolerance is due to acquired or latent intestinal lactase deficiency in the majority of cases. The reason for the variable results obtained in the literature is discussed.

When a shock wave moving through an isentropic ideal gas catches up with, and passes into a simple expansion wave, the shock decays. Because of this the gas will not be isentropic in the region behind the shock. The problem of determining the motion of the gas in this region is as yet unsolved. In this paper we introduce a simple compression wave behind the shock which catches up with it at the instant of its entry into the leading expansion wave. This second wave is chosen so as to counteract the decaying effect of the first, and keep the shock strength constant throughout the motion. We assume the first wave to be point-centred, and caused by the withdrawal of a piston at a finite velocity from a gas at rest in a shock tube. After a finite time the piston is halted causing the shock. The problem is then to determine the subsequent motion of the piston to produce a compression wave with the desired property.

Two patients with long standing malabsorption developed intestinal ulcers and died. The ulcers were associated with scattered microscopic aggregates of lymphoma in the intestinal mucosa without the production of a tumor; it is suggested that the lymphoma caused the ulceration. Histological features which point to the presence of lymphoma are defined and a pathogenesis for ulceration is proposed. Evidence is presented to show that these patients did not have adult celiac disease. It is concluded that the lymphomatous process caused the entire clinicopathological syndrome. This may also apply to a majority of patients who have intestinal lymphoma and steatorrhea.

A case of massive jejunal diverticulosis is described. The condition was complicated by small intestinal bacterial overgrowth which lead to steatorrhoea, vitamin B12 deficiency and subacute combined degeneration of the cord. Conventional treatment may not completely eliminate the abnormal microflora. In severe jejunal diverticulosis with neurological complications long term replacement with vitamin B12 is recommended.

A retrospective study was conducted to assess the association of alpha-gliadin antibodies with intraepithelial lymphocyte counts. Twelve subjects with apparently normal small intestinal histology and raised alpha-gliadin antibody titres had significantly increased intraepithelial lymphocyte counts (42 (SEM) 5.9) when compared with 16 subjects with normal alpha-gliadin antibody titres (17 (3.2); p less than 0.001). These findings show that in the absence of gross pathology raised alpha-gliadin antibody titres are associated with increased numbers of intraepithelial lymphocytes and may reflect continuous immunological processes in the small intestine.

The standard double-isotope Schilling test was used to study vitamin B12 absorption in seven patients with obstructive jaundice and 10 with T-tube bile duct drainage after cholecystectomy and bile duct exploration. In three and five of these patients respectively absorption was impaired. In the second group six patients were restudied after removal of the T tube, and in each case absorption was improved. Similar results were obtained after bile duct ligation in rats. Bile exclusion produced a 50-60% reduction in renal and hepatic uptake of vitamin B12 from the intestinal lumen. The malabsorption was corrected by replacing bile. These studies suggest that bile plays a part in the normal absorption of vitamin B12.

1. Folate deficiency is reported in association with certain malignant tumours, and it has been suggested that this arises from increased folate turnover and catabolism in such circumstances. 2. Using an experimental animal model to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of the two urinary catabolites p-[3H]aminobenzoylglutamate and [3H]acetamidobenzoylglutamate, we have measured the rate of folate catabolism in mice with ascitic tumours. 3. There was a significant increase in the rate of catabolism in the mice with tumours compared with controls over a 10 day period. This was associated with the accumulation of ascitic fluid and an increase in the number of tumour cells in the treated animals. 4. The increase in catabolism appeared to be due to increased cell turnover of the tumour rather than an increase in cell mass, as the increase in mass of the tumour was negligible.

Histiocytic medullary reticulosis (HMR) has been regarded as a rapidly progressive disorder with death commonly occurring within 6 months of onset. A case with the typical features of this disease is described in which a complete remission followed combination chemotherapy.

Evidence has been furnished confirming the presence of an iron-binding component gastroferrin, in human gastric juice The unusual iron-saturation curve shown by gastroferrin— increased iron-binding with increased iron concentration but total loss of iron binding beyond a certain concentration-is a consequence of its precipitation with the iron it has been holding in solution. Since carbohydrate but no measurable amount of protein is lost from solution, it seems reasonable to conclude that although gastroferrin may contain some protein it is essentially carbohydrate.

Twenty patients with duodenal ulcer have been treated by a pylorus-preserving gastrectomy. A functioning pyloric sphincter was maintained by retaining a 2-cm. cuff of antrum and carrying out a Billroth-I type of resection proximally. Basal acid output was reduced by 52.4 per cent and maximal acid output by 65 per cent. Gastric emptying time was prolonged, without producing stasis. A provocative test for the presence of dumping produced symptoms in only 1 patient following this operation in comparison with a high incidence of symptoms in patients who had had a Polya gastrectomy or vagotomy and drainage. The results suggest that the procedure may be of value in the treatment of chronic duodenal ulcer.

Monoclonal antibodies to monomorphic determinants of the MHC class II region products, HLA-DR, DP and DQ were used to investigate their expression on cells of the normal and coeliac (both treated and untreated) small bowel. HLA-DR antigens showed a characteristic distribution in the normal small bowel: epithelial cells in the apical portions of the villi stained heavily, and this staining decreased in intensity towards the villous base. The crypt epithelial cells were clearly unstained. Stellate cells within the lamina propria were also HLA-DR positive. HLA-DP antigens showed a similar distribution, although the intensity of staining was less than that seen with HLA-DR. HLA-DQ antigens were absent from epithelial cells and were confined solely to cells within the lamina propria. In untreated coeliac disease, the intensities of both HLA-DR and HLA-DP were increased, and in addition a more extensive distribution of these antigens was observed. In addition to occurring on the surface epithelial cells, DR and DP antigens were now present on crypt epithelial cells. Despite this change in expression of DR and DP antigens, the distribution of HLA-DQ was essentially unaltered from that of the normal small bowel. The findings in treated coeliac disease were intermediate between those in the normal and untreated coeliac small bowel. The differential expression of class II antigens by normal and diseased small bowel epithelium which has been demonstrated may have implications for interactions of these cells with cells of the immune system.

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies — an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p < 0.005), though the sensitivity of each test was less than 70%.

It has recently been suggested that a number of small bowel lymphomas arise from histiocytic cells in the intestine. This has been referred to as malignant histiocytosis of the intestine (MHI) (Isaacson et al, 1979). Three such patients with small bowel malabsorption had the following features: subtotal villous atrophy of the jejunum, generalized ichthyosis, fever and lymphopenia are described. In all three, the bone marrow appearances were similar to those seen in histiocytic medullary reticulosis (HMR) (ScottRobb-Smith, 1939). A tumour was present in the small bowel and/or mesentery of all patients and the histological lesion was similar to that described as MHI. Two patients had a response to combination chemotherapy. One patient had a complete remission of his disease but this relapsed after 1 year and proved refractory to chemotherapy. A second patient died following chemotherapy with gastro-intestinal perforation and septicaemia and the third patient died shortly after diagnosis and before chemotherapy could be commenced. It is suggested that the combination of signs, symptoms and pathological features described may reflect a specific clinical entity which has not previously been described.

At present the effects of maintenance treatment for peptic ulcer disease are usually calculated by using 'life-table' analyses. Whilst these accurately demonstrate the speed with which an initial relapse occurs they make no allowance for the fact that, in clinical practice, a relapse often responds to a further course of full-dose treatment and the patient then returns to maintenance therapy. A further compounding factor is that, in any long-term study, patients will be lost to follow-up for a variety of reasons not all related to failure of the treatment. In this paper we describe the use of 'prevalence rates' to better reflect the outcome of peptic ulcer management. Three 'computer models', which have been developed to address the problems of patients leaving the study for any reason during such a long time-period, are also described, as are the underlying assumptions made. Using the results from a long-term study of continuous treatment with cimetidine, the 'prevalence rates' of ulcer disease over 6 years were calculated. Observed relapse rates appeared to fall with time (from 2.7% for duodenal ulcer (DU) and 2.5% for gastric ulcer (GU) to 1% and 2% respectively). However, on applying the models to the data, prevalence rates tended to rise slowly with time for the first 3 years in each of the models tested. At 6 years, two of the models suggested that the prevalence rate for DU would be about 8%; this is not very different to the reported recurrence rate after surgical treatment by truncal vagotomy and pyloroplasty. It is concluded that 'prevalence rates' should be used to assess long-term medical treatments for ulcer disease. Similar methods could also be used to examine the medical treatment of any other disease where multiple relapses, capable of responding to re-treatment, occur. The use of models proved beneficial in compensating for patients lost during the study.

The synthesis of liver pteroglutamates (folates) from injected [ 3 H]- pteroyglutamic acid was investigated in vitamin B-12 methione-deficient rats and pair-fed controls using improved extraction and chromatographic procedures to identify the monoglutamyl derivatives present. Livers from deficient animals had significantly increased levels of radioactive 5-methyltetrahydro- pteroylglutamine detected after conjugase treatment of extracts and significantly decreased levels of radioactive tetrahydropteroylglutamate and formylated derivatives. However, that this is only a temporary effect and the result of a decreased rate of equilibration of the exogenous radioactivity was shown by measuring the fully equilibrated endogenous pools. This was done by microbiological assay of the endogenous liver folates with Lactobacillus casei . No significant difference was found between deficient animals and controls in the proportion of the endogenous microbiology active derivatives present. These results in the rat do not support the idea in vitamin B-12 deficiency the cellular folates accumulates as the reduced 5-methyl derivative, resulting in inadequate amount of the other cofactors to participate in nucleic acid biosynthesis.

Using 5-[14C] methyltetrahydropteroylglutamate and [3H] pteroylglutamate it was found that vitamin B12 dependent methyltransferase can be inhibited in vivo in mice by nitrous oxide. Examination of the liver [3H] folates showed as expected that both controls and nitrous oxide treated mice had synthesised the reduced 5-methyl form. However, the controls had converted [3H] almost exclusively into a polyglutamate with virtually no monoglutamate present, while nitrous oxide treated mice had failed to add glutamates to over half of the incorporated folate. Thus in vivo demethylation may be necessary prior to polyglutamate biosynthesis and act as a method of controlling folate accumulation, or be used to create a concentration gradient with the circulating folate.

1. The recent suggestions that folate polyglutamate biosynthesis demonstrated in vivo with [3′5′9(n)-3H]folic acid is due to exchange and cannot be achieved with [2-14C]folic acid has been demonstrated to be untrue. 2. The compounds formed with both types of radioactive tracer have been shown to be folate polyglutamates from their elution position from precalibrated ion-exchange columns and their susceptibility to hydrolysis by a γ-carboxypeptidase (conjugase) from human sera. 3. By the use of the methods involving [2-14C]folic acid, reported by others to give only folate monoglutamates, we have been able to demonstrate clearly the presence of folate polyglutamates.

Twenty-nine patients with normal blood lipids were placed on diets. Thirteen, mainly attending hospital for varicose veins, were prescribed low-energy diets: HDL-cholesterol was raised after one month and significantly after three months (P less than 0.02); total cholesterol was lowered (P less than 0.05). Sixteen patients, mainly with irritable bowel symptoms, were prescribed high-fibre diet: HDL-C was raised after one month (P less than 0.05), but not significantly so after three months; total cholesterol was unchanged.

Serum folate and vitamin B12 concentrations in early pregnancy were compared for 32 mothers with pregnancies affected by neural tube defects and 395 randomly selected pregnant control women from the same maternity hospitals. No significant differences were found between the affected mothers and the controls in the median values and frequency distributions of either vitamin. Sixteen of the samples from mothers whose infants had neural tube defects were taken between 9 and 13 weeks' gestation and 11 of these had both serum folate and vitamin B12 concentrations within the normal ranges for our laboratory. These findings are discussed in relation to the concept of folate deficiency as a major factor in the aetiology of neural tube defects.

It is suggested that in man the methyl folate trap is a normal physiological response to impending methyl group deficiency resulting from a very low supply of methionine. This decreases cellular S-adenosyl-methionine (SAM), which puts at risk important methylation reactions, including those required to maintain myelin. In order to protect these methylation reactions, the cell has evolved two mechanisms to maintain supplies of methionine and SAM as a first priority. (a) Decreased SAM causes the folate co-factors to be directed through the cycle involving 5-methyl-tetrahydrofolate (5-methyl-THF) and methionine synthetase and away from the cycles that produce purines and pyrimidines for DNA synthesis. This enhances the remethylation of homocysteine to methionine and SAM. In addition, by restricting DNA biosynthesis and with it cell, division, competition for methionine for protein synthesis is reduced. Thus, whatever methionine is available is conserved for the vital methylation reactions in the nerves, brain, and elsewhere. (b) 5-methyl-THF, the form in which almost all folate is transported in human plasma, must react with intracellular homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine, methionine deficiency will cause intracellular folate deficiency, and the rate of mitosis of rapidly dividing cells will be reduced. although these two processes have evolved as a response to methionine deficiency, they also occur in B12 deficiency, which the cell mistakenly interprets as lack of methionine. the resulting response is inappropriate and gives rise to a potentially lethal anaemia. In these circumstances the methylation reactions are also partly protected by the reduced rate of cell division. This explains why administration of folic acid, which induces cell division and use of methionine in protein synthesis, impairs methylation of myelin and precipitates or exacerbates subacute combined degeneration (SCD). During folate deficiency methionine biosynthesis is also diminished. As in methionine deficiency, the body responds to decreasing availability of SAM by diverting folate away from DNA biosynthesis towards the remethylation of homocysteine to methionine and SAM. The selective use pf available folate to conserve methionine, together with the ability of nerve tissue to concentrate folate form the plasma, explains the absence of SCD in folate deficiency.

Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group of untreated and treated coeliac patients and non-coeliac control subjects was performed using monoclonal antibodies and an immunoperoxidase technique. A characteristic cellular distribution was observed within the normal mucosa. The intraepithelial and lamina propria compartments were occupied mainly by T suppressor/cytotoxic and T helper/inducer cells respectively. Further subdivision of lamina propria T helper/inducer cells with the Leu 8 antibody revealed that these were of the Leu 3a+ Leu 8- phenotype. Macrophages, defined by the RFD7 antibody, were seen to occupy the same microenvironment as T helper/inducer cells. T cells expressing the T cell activation antigen defined by anti-Ta1 were found with the normal lamina propria, although few cells were identified by the anti-Tac antibody. HLA-Dr antigens were expressed by stellate cells within the lamina propria, and also by the epithelial cells of the villi, but not by normal crypt epithelial cells. In untreated coeliac patients the distribution of the various cell types was essentially unchanged, although the number of these cells was markedly increased, including those which expressed the Ta1 antigen. A significant deviation from normal in the expression of HLA-DR antigens was found in the coeliac small bowel: these antigens were expressed not only on the villous epithelial cells but also on the epithelial cells of the crypts. Immunohistological findings in the treated coeliac patients were intermediate between the normal and untreated coeliac groups, and were completely normal in those patients with complete histological resolution of their disease. These results suggest that coeliac disease is accompanied by an enhanced stimulation of the normal mucosal immune response and do not imply a primary pathogenic role for the immune system in this disease.

Features that might distinguish uncomplicated coeliac disease from enteropathy associated T cell lymphoma were investigated. Of 76 patients with coeliac disease, 71 (93%) had raised levels of alpha gliadin antibody and all responded clinically and histologically to treatment with a gluten free diet. In contrast, none of 16 patients with enteropathy associated T cell lymphoma had raised levels of alpha gliadin antibody, and treatment with a gluten free diet resulted in histological improvement in one and transient clinical improvement in six patients. The ratio of women to men was 2.2:1 in the group with coeliac disease and 1:1.6 in the patients with enteropathy associated T cell lymphoma. Thus patients with enteropathy associated T cell lymphoma do not display a humoral immune response to wheat protein (alpha gliadin), rarely respond to a gluten free diet, and are often men. Patients with uncomplicated coeliac disease usually have raised levels of alpha gliadin antibody, always respond to a gluten free diet, and are frequently women. These findings suggest the presence of two separate forms of enteropathy: one is benign and sensitive to wheat protein whereas the other runs a malignant course.