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Objective Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting. Methods Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease. Response to treatment and other clinical events were monitored over the ensuing years. Results Untreated coeliac disease was diagnosed in 97 patients and was excluded in 344. At clinical presentation, the endomysial antibody test was positive in 84 of the 97 untreated coeliac patients (sensitivity 87%) and negative in 340 of the 344 non-coeliac patients (specificity 99%). A typical histological lesion was found in 83 of the 97 coeliac patients (sensitivity 86%) but was absent in all 344 non-coeliacs (specificity 100%). The sensitivity of the gliadin antibody test was 69% and the specificity was 71%. Conclusions In unselected patients attending a gastroenterology clinic, small bowel histology and endomysial antibody serology show similar predictive value in the diagnosis of coeliac disease. These results emphasize that a combination of clinical, histological and serological criteria are required for effective diagnosis of this disorder. Exclusive reliance on histology or serology will result in failure to make a diagnosis in a significant proportion of patients.

InP‐based high‐electron mobility transistor (HEMT) structures have been grown containing strained In1−xAlxP Schottky layers with x=0.15–0.25. The band gaps of the strained layers in the HEMT structure were determined by photoreflectance spectroscopy. For x=0.15, Hall mobilities were comparable to those obtained in an analogous InAlAs/InGaAs structure. Lower mobilities were obtained with higher x value. Misfit dislocations were observed in plan view transmission electron microscopy for x=0.25 but not x=0.15. HEMT structures were also grown with InAsP channel layers containing moderate sheet densities. Photoluminescence measurements of the quantum well region indicated transitions to two electronic subbands. The InAs1−xPx composition was found to be weakly dependent on the phosphorus flux and uniform on 2 in. wafers.

The effect of organic solvent load on the radial emission profiles for Mg I, Mg II, C I, C2, and CN was measured. The three dimensional information reveals the observation zones where the emission intensity of these species is proportional to solvent load and plasma excitation conditions.

With the use of noise power spectra it is shown that the vortex shedding frequency depends on the solvent and the solvent plasma load, and modulates both the plasma boundary and analyte plume of the discharge.

Ga0.5In0.5P/GaAs heterojunction films were grown using a valved, three‐zone phosphorus source and valved arsenic source. The design of the phosphorus source eliminates the flux bursts experienced upon valve opening with two‐zone furnaces. Narrow x‐ray linewidths with Pendellosung interference oscillations were observed in double crystal measurements. Chemically abrupt As/P and P/As interfaces were obtained using both valved sources. The optical band gap determined from photoluminescence was consistent with minimal ordering in the films. GaInP films were doped with silicon in the 1017 cm−3 range with good mobilities and negligible carrier freeze‐out upon cooling. A GaInP(emitter)/GaAs(5×1019 cm−3 carbon doped base) heterojunction bipolar transistor exhibited a current gain of 30.

Carbon‐doped GaAs films have been grown by molecular‐beam epitaxy using carbon tetrabromide as the carbon source. The films were doped up to 1.3 × 1020 cm−3 with mobilities which compare favorably to beryllium‐doped films. Secondary‐ion mass spectrometry measurements made on these films indicate sharp transitions and negligible memory effects as well as near unity doping incorporation. Room temperature photoluminescence intensities were equivalent to comparably beryllium‐doped films at 5.0 × 1019 cm−3. Photoluminescence intensities and hole concentrations were found to be dependent on both arsenic to gallium flux ratios and substrate temperature. Annealing studies on a film doped with carbon at 4.6 × 1019 cm−3 indicate good thermal stability of the carbon in the arsenic lattice site.

The effect of solvent and solvent load on the background spectra and visual features obtained from an inductively coupled argon plasma have been recorded. An experimental system for making these measurements is described. The solvents studied were water, methanol and chloroform, at solvent loads corresponding to the maximum and minimum obtainable. The most conspicuous features observed were emission atomic carbon, diatomic carbon and cyanide. A thermal pinch created by the introduction of organic solvents and a recirculation eddy at the base of the torch have been characterized.

The effect of chloroform load on the axial emission profiles for Mg I, Mg II, C I, C2, and CN was measured. The emission intensity ratio of Mg II : Mg I was used to indicate the ‘robustness’ of the plasma at r.f. powers of 1.0, 1.25, and 1.50 kW and central channel gas flow rates of 0.6–0.9 l min–1 over the accessible range of solvent load. The C2 and CN emissions mark the boundries of the aerosol channel and the edge of the atomic plasma in the ‘tailflame’ region.

GaAs films doped with boron in the 1020 cm−3 range were grown by solid source molecular‐beam epitaxy. Lattice contractions were observed in x‐ray double crystal spectra. Substitutional boron concentrations up to 1.7×1020 cm−3 were obtained with narrow x‐ray linewidths and specular surface morphology. For a given boron flux, the substitutional concentration was dependent on growth temperature. P‐type conductivity due to boron incorporation was measured in the films with hole concentration reaching 1×1019 cm−3. The lattice contractions exhibited good thermal stability for rapid thermal anneals.

Heterojunction bipolar transistor (HBT) structures with heavily carbon and beryllium doped base layers were grown in a conventional molecular‐beam epitaxy (MBE) environment. The current gain in the carbon doped structures was reduced by enhanced bulk recombination. For a hole concentration of 5 × 1019 cm−3, the carbon concentration exceeded the hole concentration and is a likely cause of the enhanced recombination. Growth conditions were determined which minimized beryllium diffusion for HBT structures with base layers doped to 1.2 × 1020 cm−3. Lattice contractions were observed at high beryllium doping concentrations. The expected reduction in resistivity with increased beryllium base doping was obtained in the HBT structures. Using HBT structures doped with beryllium at 5 × 1019 cm−3, high‐power performance was obtained at 10 GHz.

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.

1. It has previously been shown that folate polyglutamates in the rat are catabolized almost exclusively via cleavage of the C-9—N-10 bond, resulting in the formation of pteridines and p-aminobenzoylglutamate. The latter catabolite is rapidly excreted, appearing in the urine as acetamidobenzoylglutamate and is undetectable in rat liver. 2. The pteridines catabolites on the other hand are retained to a much greater extent by the liver, forming an ever-increasing proportion of the retained radioactive tracer. 3. A possible role for these pteridines as cofactors in brain metabolism is discussed.

Summary. 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) (Scott & Robb-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.

The diagnostic value in coeliac disease of circulating antibodies to casein, crude gliadin, and alpha gliadin was assessed using an adaption of the enzyme linked immunosorbent assay system. alpha Gliadin was the only antigen which consistently separated 26 patients with untreated coeliac disease from 26 normal controls and 13 patients with chronic inflammatory bowel disease. The mean assay index for the 26 patients was 3.1 (SD 1.2) compared with 1.05 (0.5) for the normal controls and 1.1 (0.6) for patients with chronic inflammatory bowel disease. The alpha gliadin antibody levels of six patients with coeliac disease who had maintained a gluten free diet for at least two years were not significantly higher than normal (1.0 (0.4)). The validity of the test was determined in 90 consecutive patients who were being investigated for the presence of coeliac disease. Levels of alpha gliadin antibody were raised in 36 out of 44 patients found to have histologically proved coeliac disease and in six out of 46 subjects whose jejunal mucosa was normal. Serial alpha gliadin concentrations were measured in 12 patients with coeliac disease who had repeat jejunal biopsies performed six months after starting a gluten free diet. The levels of antibody fell in seven of the eight patients whose jejunal mucosa improved on maintaining the diet. They remained raised in four patients who did not adhere to the diet and whose mucosa did not improve. Although a test measuring alpha gliadin antibodies is unlikely to replace jejunal biopsy in the diagnosis of coeliac disease it may be useful in screening for the disease among outpatients.

NINETY-TWO new patients with Crohn's Disease presented to three South Dublin hospitals from 1975–1980.

1. 1. Prior administration of methotrexate reduces the 24-hour incorporation ofparenteral [ 3 H]pteroylglutamate by rat liver from 30% to less than 2%. 2. 2. The folate compounds synthesized showed the same ratio of reduced 5-methyl- and 5-formyl-derivatives as normal but the number of glutamyl residues to which these were attached was reduced. No polyglutarnyl forms of unreduced pteroylglutamate were found. 3. 3. Under similar conditions, 10% of a parenteral dose of [ 3 H] methotrexate was incorporated into the liver and a small proportion of this was converted to conjugated forms of unreduced methotrexate. Kidney also demonstrated the ability to conjugate methotrexate.

PUBLISHED, T helper and suppressor cell control of autologous immunoglobulin production was measured in 14 patients with Crohn's disease (CD) using autologous B cells or monocytes to stimulate regulatory T-cell activity. A pronounced defect in suppressor cell function was observed in the patient group but not in matched controls irrespective of whether B cells or monocytes were used as the stimulus. This defect was observed for IgG, A and M. This defect was seen both in patients with active disease and with inactive CD suggesting the possibility that a primary regulatory defect might exist in this disease. The patient group displayed normal helper cell function.

A group of teenage coeliac patients has been followed at three monthly intervals in the Outpatient Department to assess their progress and also to monitor their ability to maintain a gluten-free diet. After a follow-up period of four to six years a detailed reassessment was carried out in hospital on 10 patients, only five of whom had persevered with a gluten-free diet. The jejunal mucosal histology of those patients who did not persist with a gluten-free diet remained `flat' although these patients appeared to have remitted clinically. Those subjects who did persist with a gluten-free regime had a normal or near normal mucosal histology. It was difficult on the basis of clinical, haematological, or biochemical criteria to separate the two groups. The best single assessment of whether these patients were maintaining a gluten-free diet was serial serum folate estimations. It is often extremely difficult to say whether teenage coeliac patients are keeping to their diet unless repeated jejunal biopsies are obtained, and this study suggests that serial serum folate estimations can act as a reasonable criterion of whether subjects are maintaining a gluten-free regime.

Complement activation may play an important role in the pathogenesis of coeliac disease. In the present study immunohistochemical localisation of C3 and of a neoantigen exposed only on the terminal C5b-9 complement complex has been performed on small intestinal biopsy sections from newly diagnosed untreated coeliac patients, from coeliac patients on long-term gluten-free diet and from disease controls. Levels of C3 were markedly increased in treated coeliac patients compared with controls. Staining of C3 was concentrated subepithelially and within the centre of the lamina propria. No staining was detected at these sites using antibody to the neoantigen, however, strongly suggesting that the increased levels of C3 seen in the coeliac patients was the result of increased extravasation of serum proteins rather than complement activation. Surprisingly, complement activation was detected within the glands of Brunner. Positive staining using anti-C5b-9 neoantigen was found in all coeliac patients, both treated and untreated. Three of the 13 disease controls also showed reactivity with this antibody. This novel finding suggests that Brunner's glands, hitherto largely neglected structures, may play an important role in the development of coeliac disease.

Twenty three cases of pseudomembranous colitis (PMC) occurred in three hospitals in 10 months. Retrospective analysis shows that they represented a single epidemic with a readily traceable chain of person-to-person contact within and between hospitals. Most patients had severe pre-existing illness and all had broad spectrum antibiotics, including either ampicillin/amoxycillin, a broad spectrum cephalosporin (particularly cefotaxime), or both. All patients had severe diarrhoea and all responded to vancomycin, but relapse occurred in five. Ten patients eventually died, principally because of underlying disease rather than from PMC. Failure to find fibrin thrombi in blood vessels in biopsies and the scanty distribution of non-invasive bacteria supports the concept of mucosal damage by bacterial toxin, rather than by direct infection, or ischaemia. Although environmental colonisation cannot be excluded, the observed pattern of spread suggests a major role for direct person-to-person crossinfection in the spread of disease in this outbreak.

Four pairs of monkeys were maintained in an atmosphere of nitrous oxide under conditions which had previously been shown to produce subacute combined degeneration (SCD) of the spinal cord. The diet of one of each pair was supplemented with methionine. In every case the monkey with the unsupplemented diet became ataxic at around 10 weeks and the disorder progressed over a period of 2-3 weeks until the animal was moribund. During this period there was no detectable clinical change in the monkeys receiving methionine supplementation. Microscopical examination of the spinal cord and peripheral nerves of the unsupplemented monkeys showed the classical changes of SCD. The histological changes correlated with the clinical observations. Sections from the methionine-supplemented monkeys showed no change or only slight changes. These results suggest that, in these animals, inability to resynthesise methionine from homocysteine leads to SCD. It seems probable that the primary lesion producing SCD in human beings with pernicious anaemia is also inability to maintain methionine biosynthesis.

IN a review of 6,097 necropsies over a 13 year period in Dublin, cirrhosis was found in 127 (2.1%). No increase in frequency was noted during the period under consideration. Alcohol was the aetiological factor in 57% of cases. Alcoholic hepatitis was superimposed on cirrhosis in 14% and 27 patients had alcoholic hepatitis without cirrhosis. In cases of cirrhosis, the male: female ratio was 1.4:1 but in alcoholic hepatitis without cirrhosis it was 1:1. The commonest cause of death in cirrhosis as a whole was bronchopneumonia while in alcoholic hepatitis and alcoholic cirrhosis it was liver failure. Seventeen patients (0.27%) had hepatocellular carcinoma, 15 (88%) in association with cirrhosis, nearly half (7) being in the alcoholic cirrhosis group. In Ireland hepatocellular carcinoma is an uncommon finding at necropsy and is usually associated with alcoholic cirrhosis rather than post-viral or cryptogenic cirrhosis.

Dyspepsia associated with arthritis and non-steroidal anti-inflammatory drugs (NSAIDs) is a common clinical problem. Up to 80% of deaths attributable to peptic ulceration may be associated with NSAID usage. The problem is foremost in the elderly population, in which there has been an increase both in the incidence of peptic ulcers and in the use of NSAIDs. Although the development of duodenal ulceration is not clearly associated with NSAIDs, it is accepted that these drugs increase the risk of gastric ulceration and the occurrence of peptic ulcer complications. Asymptomatic peptic ulceration is common, and patients taking NSAIDs are often asymptomatic prior to presentation with life-threatening complications. The key principle in management of this problem is prevention through careful selection of patients for NSAID use, adequate treatment of peptic ulceration and maintenance of remission. A variety of effective drugs are available for the treatment of peptic ulcers, including H2-receptor antagonists, pirenzepine, sucralfate and colloidal bismuth subcitrate. However, it is recognised that peptic ulceration is a chronic disease with a relapsing-remitting course, often with asymptomatic ulcer episodes. The knowledge that current ulcer-healing strategies do not significantly alter this natural history has lead to increasing efforts to prevent relapse with effective 'maintenance' therapy.

In a 3-centre study, 128 patients with endoscopically proven duodenal ulcers were treated with cimetidine 1g daily. One hundred and nineteen patients completed 4 weeks’ treatment: 91 of these had healed ulcers and 28 were unhealed. A further 18 patients were healed at 8 weeks and 3 more healed at 12 weeks.

The pattern of degeneration induced in the spinal cords and peripheral nerves of 4 monkeys exposed to nitrous oxide resembles subacute combined degeneration found in man with untreated vitamin B12 deficiency. Our findings indicate that nitrous oxide directly inhibits the folate dependent methionine synthetase reaction. This ultimately results in ‘methyl group deficiency’ with consequent defective remethylation of essential constituents of nerve tissue. The implications of the methyl group deficiency hypothesis are examined and its relationship to the haematological and neurological status of patients with vitamin B12 deficiency are discussed.

An improved technique for the detection of alpha-gliadin sensitised mononuclear cells in the peripheral blood of untreated coeliac patients is described. This method is a modification of the direct LMIF assay, and involves exposure of lymphocytes to alpha-gliadin and the assay of the resultant lymphokine produced using normal leucocytes as indicator cells. All untreated coeliac patients, 14 of 15 treated patients, and two of 28 controls responded to alpha-gliadin. The direct LMIF assay in comparison is less sensitive, and detected sensitivity to alpha-gliadin in only four out of eight patients with untreated coeliac disease. Use of the indirect LMIF technique demonstrates that in untreated as well as treated coeliac patients there are cells sensitised to alpha-gliadin circulating in the peripheral blood. These findings may have pathogenic and diagnostic significance.

Investigations into the standardization and reproducibility of the urinary excretion method for determining the absorption of tritiated folic acid were carried out. By proper timing of tissue-loading doses of folic acid a clear difference between the percentage excretion ranges of normal and coeliac subjects was obtained. In addition conditions were found whereby the procedure could be repeated on an individual up to four times with reproducible results. Methotrexate in pharmacological amounts was found to have no inhibitory effect on the human intestinal absorption of a small oral dose (300 mug) of folic acid as determined by this method. This indicates that reduction of folic acid is not necessary for its absorption in man.