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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 145 records · Page 8Linked to original sources

Dissociation between systemic and mucosal humoral immune responses in coeliac disease.

We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity). The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls. Serum and salivary immunoglobulin concentrations were similar in the three groups. Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects. In treated patients, with proved histological recovery on gluten free diet, serum IgA antigliadin antibody values fell to control values, though serum IgG antigliadin antibody values remained moderately raised. In contrast, there was persistence of secretory antigliadin antibodies in treated patients (particularly IgM antibody) in both jejunal aspirate and gut lavage fluid. Antibody responses to betalactoglobulin and ovalbumin were similar to those for gliadin, including persistence of high intestinal antibody values in patients with treated coeliac disease. There was a positive correlation between antibody values in jejunal aspirate and gut lavage fluid, but not between saliva and jejunal aspirate; thus salivary antibodies do not reflect intestinal humoral immunity.

Adolescent↗

Small intestinal function and dietary status in dermatitis herpetiformis.

Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal.

Adolescent↗

Animal model of gluten induced enteropathy in mice.

The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy. Additional factors, such as those occurring during intestinal anaphylaxis (increase intestinal permeability), or during graft versus host reaction (enhanced antigen presentation), seem to be necessary for the full expression of a jejunal mucosal reaction.

Anaphylaxis↗

Smoking, humoral immunity, and ulcerative colitis.

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.

Adult↗

An analysis of cases incorrectly coded as inflammatory bowel disease in Scottish Hospital In-Patient Statistics (SHIPS).

As part of a large clinical and epidemiological study of inflammatory bowel disease (IBD), we examined the hospital case records of a sample (255) of the 1257 patients aged 0-20 years, recorded in Scottish Hospital In-Patient Statistics (SHIPS) for 1968-1983 as Crohn's disease (CD) or ulcerative colitis (UC). The coded diagnosis was incorrect at the time of coding in 47 instances (18.4% of the sample), for the following reasons: clinical diagnosis wrong (24 cases); IBD correctly diagnosed but wrongly coded as CD for UC or UC for CD (seven cases): various other clerical or computer errors (15 cases). One case that did not meet standard diagnostic criteria for CD at the time of coding was shown to be correctly labelled when confirmatory pathological information became available. In view of the influence of such statistics on the social and clinical management of chronic illnesses such as IBD, and in view of the impact of analysis of these data on the provision of services and allocation of resources, it is suggested that some indication of the degree of confidence in the clinical diagnosis (possible, probable, definite) should be incorporated in the information submitted for coding and should be reflected in the derived data.

Child↗

Gut lavage fluid proteins as markers of activity of inflammatory bowel disease.

Intestinal secretions may be obtained by gut lavage using a polyethyleneglycol-based electrolyte lavage solution; concentrations of immunoglobulins and other proteins are readily measured in processed gut lavage fluid. As patients with inflammatory bowel disease (IBD) have greatly increased numbers of IgG-producing intestinal immunocytes, we measured gut lavage fluid IgG levels in 44 patients with IBD with various degrees of disease activity to determine whether total IgG in gut lavage fluid reflects disease activity. We also measured levels of albumin in gut lavage fluid, to determine the degree of plasma leakage. Both IgG and albumin levels in the patients with active IBD were significantly higher than those in controls and patients with inactive IBD (all p less than 0.00001). IgG is a more specific index of disease activity than albumin, with no overlap between levels in controls and patients with active IBD. There was a positive correlation (r = 0.68, p less than 0.0001) between IgG and albumin levels, suggesting that gut lavage fluid IgG is mainly plasma-derived.

Adolescent↗

The clinical entity of orofacial Crohn's disease.

The clinical features, treatment and outcome of 29 patients with oral Crohn's disease seen over a 6-year period have been reviewed. Findings on clinical examination included labial swelling (19 patients), buccal mucosal cobblestoning (11), linear ulceration (11), lumps (five), and mucosal tags (two). Eleven patients had multiple features. Eight patients developed symptoms within the first decade of life and nine patients had symptoms for more than 4 years before diagnosis; the mean age at diagnosis was 30 (range 6-78) years. Fourteen of these patients (48 per cent) have Crohn's disease elsewhere in the alimentary tract, and in nine patients the oral disease predated the development or detection of Crohn's disease at other sites. Eight patients (25 per cent) have required no specific therapy for their oral disease and 12 have been treated with systemic corticosteroids of whom three are steroid-dependent. No other pharmacological approach to treatment has been successful and elimination diets, tried by five patients, had no effect. Oral Crohn's disease has a characteristic naked-eye appearance, may be the first or only manifestation of Crohn's disease and usually improves with oral corticosteroid treatment.

Adolescent↗

Similarities in intestinal humoral immunity in dermatitis herpetiformis without enteropathy and in coeliac disease.

Intestinal humoral immunity was examined in eight patients with dermatitis herpetiformis and normal jejunal histology (as determined by quantitative morphometry) on a gluten-containing diet. Jejunal aspirate was taken at the time of jejunal biopsy, and levels of total immunoglobulins (IgA, IgM, IgG) and specific antibody to gliadin and two other dietary proteins, betalactoglobulin and ovalbumin, were measured. The pattern of secretory immune responses in the dermatitis herpetiformis patients was similar to that in twenty-six patients with untreated coeliac disease--ie, higher than normal concentrations of IgA, IgM, and IgG and high levels of specific antibodies (IgA and IgM) to the three dietary proteins. Serum levels of IgA antigliadin were similar in the dermatitis herpetiformis and control (twenty-eight patients who underwent jejunal biopsy to exclude coeliac disease) groups, and serum levels of IgG antigliadin were intermediate between those of the control and coeliac disease groups. These findings suggest that investigation of gut humoral immunity may provide a diagnostic index of latent coeliac disease. The definition of coeliac disease as a permanent gluten-sensitive enteropathy may have to be revised if the proposed two-stage model is confirmed.

Adolescent↗

Cardiopulmonary resuscitation--a teaching guide.

As a teacher working in an acute area--Accident and Emergency, I have been concerned for some time about the teaching input on the curriculum for cardiopulmonary resuscitation. In my experience, the students are given a short lecture on the procedure for calling an arrest team in the introductory unit and this is followed by a more in-depth lecture in their final year prior to commencing their clinical allocation on an acute unit such as accident and emergency or intensive care. I have found this to be inadequate as students are, in their own opinion, highly stressed by the thought of dealing with an arrest situation and the skills they demonstrate in their third year are, in my opinion, also inadequate. In my own hospital, we are fortunate to be one of the few centres which train the general public in how to deal with arrest situations in the home or work environment. I, am a trainer on this programme and have successfully argued for a similar programme to be incorporated into the introductory unit of the students' course. What has become clear is that other teachers are equally unnerved by the thought of a cardiac arrest and willingly admit to being inefficient at the actual resuscitation procedure. As a result, I have written teaching guidelines which should help those less experienced at cardiopulmonary resuscitation and will provide them with the necessary information which can be passed on to students.

Attitude↗

Minisatellite DNA fingerprints of salmonid fishes.

The human minisatellite probes 33.6 and 33.15 cross-hybridized to DNA digests of Atlantic salmon, brown trout and rainbow trout revealing complex multi-banded patterns. These DNA fingerprints (in excess of 40 resolvable fragments in some cases) were highly polymorphic, individual specific and found to be stable, both somatically and in the germline. Pedigree analysis of an Atlantic salmon family confirmed that the minisatellite fragments showed Mendelian inheritance. With only a single occurrence of linkage and allelism being observed it is likely the minisatellite loci are widely distributed throughout the salmonid genome. The potential applications for both multi- and single locus minisatellite probes in salmonid research are discussed.

Animals↗

Appraisal of gut lavage in the study of intestinal humoral immunity.

Direct investigation of intestinal humoral immunity requires collection of intestinal secretions or mucosal biopsy specimens, or both. A non-invasive technique of gut lavage, with a polyethyleneglycol electrolyte lavage solution as a means of collecting intestinal secretions for immunoglobulin and antibody studies, was evaluated. Fifty patients were studied--25 immunologically normal patients or volunteers, 15 patients with untreated coeliac disease, and 10 patients with active Crohn's disease. Protease inhibitors were added promptly to samples to prevent proteolysis of immunoglobulin content. Treated lavage samples were assayed by enzyme linked immunosorbent assay for immunoglobulin and antibody content. Studies of serial lavage specimens showed that early, faecally contaminated specimens contained negligible quantities of immunoglobulin, but once the specimens became clear a steady state was reached, with little variation in immunoglobulin content between serial specimens and with a uniform dilution (around 20%) of the ingested polyethyleneglycol. Gut lavage fluid IgA was predominantly secretory, comprising 92%, 81.6%, and 76.7% respectively of the total IgA gut lavage fluid content in the control, coeliac, and Crohn's groups. High values of total IgM and IgA and IgM antigliadin antibodies were detected in the coeliac group, and high values of IgG in the Crohn's disease group. This method of gut lavage is not only an effective bowel cleanser, but also a noninvasive means of obtaining intestinal secretions for the study of humoral immunity in gastrointestinal disease.

Adolescent↗