Biomedical subjects

W S Selby

Publications and source records attributed to W S Selby.

At least 19 recordsLinked to original sources

PubMed1992

Antibiotic-associated colitis and cystic fibrosis.

The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed.

Adult↗

PubMed1992

Sclerosing cholangitis and biliary tract calculi--primary or secondary?

The clinical features of 61 patients with sclerosing cholangitis were reviewed. This group included 23 patients with biliary tract calculi, commonly considered as excluding the diagnosis of primary sclerosing cholangitis. The aim of this study was to compare these 23 patients (group A) with 38 patients with sclerosing cholangitis free of calculi (group B). Both groups had the following features in common: (i) age at presentation, (ii) incidence of inflammatory bowel disease, (iii) extent of radiological disease, (iv) prevalence of HLA-B8 and DR3 haplotype, (v) incidence of cholangiocarcinoma, and (vi) progression to hepatic transplantation (mean follow up 49.9 months). All patients in group A were symptomatic at diagnosis compared with 23 of the 38 patients (61%) in group B. Recurrent ascending cholangitis occurred in 12 patients in group A (52%) and two patients (5%) in group B. The similarity between the two groups was maintained when the nine patients in group A who developed calculi after sclerosing cholangitis was diagnosed were excluded. It is concluded that choledocholithiasis is part of the spectrum of primary sclerosing cholangitis and that it is not necessary to invoke choledocholithiasis as the initial lesion of the bile ducts in such patients.

Adolescent↗

PubMed1986

Serum autoantibodies, ulcerative colitis and primary sclerosing cholangitis.

The aetiology of primary sclerosing cholangitis is unknown, but it is closely associated with ulcerative colitis. Serum anticolon antibodies, crossreacting with portal tracts, have been reported in patients with ulcerative colitis but no studies have been carried out in primary sclerosing cholangitis. The frequency of serum anticolon antibodies and portal tract antibodies have been measured in 24 patients with primary sclerosing cholangitis and ulcerative colitis; 15 patients with primary sclerosing cholangitis without ulcerative colitis; 77 patients without primary sclerosing cholangitis: 25 patients with Crohn's colitis; 10 patients with primary biliary cirrhosis; 22 patients with extrahepatic biliary obstruction and 20 normal controls. Serum anticolon and portal tract antibodies were detected using immunoperoxidase techniques on normal colon and obstructed human liver. Tissue typing was undertaken using a standard microcytotoxicity technique. The frequency of anticolon antibodies was markedly increased in primary sclerosing cholangitis patients with ulcerative colitis (62.5%) compared with patients with ulcerative colitis (17%) and Crohn's colitis (16%) (chi 2 = 17.9; p less than 0.001). The antibodies were almost entirely of IgG and IgA classes in all groups. Anticolon antibodies were not found in sera from any other group. Sera from eight of 15 patients with primary sclerosing cholangitis, ulcerative colitis and anticolon antibody reacted with portal tracts of human obstructed liver. This reaction was also seen in four of nine patients with ulcerative colitis and primary sclerosing cholangitis and in three of 15 patients with primary sclerosing cholangitis alone. Portal tract antibody was of IgG class and was not present in sera from any other groups. Unlike anticolon antibody, there was a close relationship between HLA-B8 phenotype and the portal tract antibody (p<0.02; chi 2 = 6.04). Absorption studies confirmed that the anticolon antibody is distinct from portal tract antibody.

Autoantibodies↗

PubMed1986

Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis.

A prospective double blind controlled trial was undertaken to examine the role of metronidazole as an adjunct to corticosteroids in the management of severe ulcerative colitis. Thirty nine patients with severe ulcerative colitis were randomised on admission to hospital to receive either intravenous metronidazole 500 mg eight hourly (19 patients) or an identical intravenous placebo (20 patients). The two groups were similar with respect to age, sex, and the extent of colitis. In addition all patients received a standard intravenous regimen consisting of methyl prednisolone 16 mg six hourly and parenteral nutrition together with a twice daily hydrocortisone 100 mg enema. Treatment was continued for five days when the patients were formally assessed. Fourteen of 19 patients (74%) receiving metronidazole and 14/20 (70%) receiving placebo were substantially improved, or in remission at the end of five days. Five patients treated with metronidazole and six with placebo had no improvement and all proceeded to urgent colectomy with no operative mortality. There were three late deaths, one in the metronidazole and two in the placebo group. These results do not support the routine use of intravenous metronidazole in the treatment of severe ulcerative colitis.

Adolescent↗

PubMed1985

Olsalazine in active ulcerative colitis.

Olsalazine (azodisalicylate) is a new drug in which two molecules of 5-aminosalicylic acid are linked by an azo bond. Its role in the treatment of mildly active, distal ulcerative colitis was investigated. Sixty patients were randomly allocated to receive olsalazine 1 g or a placebo as a retention enema nightly for two weeks. Clinical improvement was seen in 19 (66%) and sigmoidoscopic improvement in 17 (59%) of the 29 patients receiving olsalazine compared with 12 (43%) and 11 (39%), respectively, of the 28 in the control group. These differences were not significant. In a second trial 40 patients were randomised to receive oral olsalazine 2 g daily or a placebo capsule for two weeks. Significant clinical and sigmoidoscopic improvement was seen in the patients receiving oral olsalazine compared with the patients receiving placebo capsules. Oral olsalazine may be valuable in the treatment of mildly active ulcerative colitis. Its role in maintaining remission is yet to be determined.

Administration, Oral↗

PubMed1985

Isolation studies--intestinal T lymphocytes.

Despite the variation in results of studies on isolated intestinal mucosal T cells obtained in different laboratories, it can be said that: 1) T lymphocytes and their subsets can be isolated from normal and from diseased intestinal mucosa. 2) Most of the functions of these T cells are, as far as has been studied, similar to those of peripheral blood T tions of T lymphocytes and the different distribution of these antigens between intestinal epithelium, which normally shows strong expression of HLA-A,B,C antigens but weak or no expression of HLA-DR antigens, and the lamina propria, which contains large numbers of histiocytic cells which are rich in HLA-DR antigens, may be vital to the functions of intestinal T cells. Removal of cells from the close association with these antigens may therefore alter their functions. Secondly, studies of isolated cell populations must be interpreted in combination with morphological examination of cell populations in situ. Such an approach will increase our understanding of the role of T cells in gut immunity in health and disease.

Cell Separation↗

PubMed1984

Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques.

Lymphocyte subpopulations in the intestinal mucosa of patients with ulcerative colitis or Crohn's disease have been studied using a double marker immunofluorescence technique. Analysis of tissue sections revealed that the majority of intraepithelial lymphocytes (IEL) were T cells (Hle-1+ HuTLA+ UCHT1+). Of these, over 80% were of suppressor-cytotoxic phenotype (OKT8+:83 +/- 10.2%) with a small population of helper type IEL (OKT4+). Only one third of OKT8+ IEL reacted with the T cell antibody, anti-Leu-1. IEL were also Tac-, C3b-receptor- (C3RT05-), and Ig-. Within the lamina propria, OKT4+ T cells predominated (ulcerative colitis 64 +/- 6.0%; Crohn's disease 63 +/- 6.0%). Less than half of the smaller OKT8+ population in the lamina propria was Leu-1+. These finding did not differ from those seen in histologically normal tissues from controls, and are similar to those reported in the small intestine. Mononuclear cells were also isolated from the intestinal lamina propria using an enzymatic technique. The majority of lymphocytes obtained were T cells (OKT3+), with populations of OKT4+ and OKT8+ cells. Comparison of the ratio of OKT4+ to OKT8+ lymphocytes determined by immunohistological analysis with that obtained in mucosal isolates, however, suggested that the isolation procedure may deplete OKT8+ cells. These findings indicate that an imbalance of mucosal immunoregulatory T cells, as defined by monoclonal antibodies, does not occur in inflammatory bowel disease. They also emphasize that functional studies of isolated intestinal mucosal cells should be combined with morphological studies of cell populations in situ.

Adolescent↗

PubMed1984

Alpha 1-antitrypsin serum concentration and phenotypes in ulcerative colitis.

96 unrelated patients suffering from ulcerative colitis were typed for the electrophoretic variants of alpha 1-antitrypsin (alpha 1-AT). None of the phenotypes showed a definite association with this condition. The serum concentration of alpha 1-AT was increased compared with healthy control subjects. There was a positive correlation between the serum concentration of alpha 1-AT and activity of the ulcerative colitis.

Adolescent↗

PubMed1984

Topical treatment of distal ulcerative colitis with 4-amino-salicylic acid enemas.

Enemas of 4-amino-salicylic acid (4-ASA) have been compared with placebo enemas in a double-blind study for the treatment of distal ulcerative colitis of mild to moderate severity. 30 patients were randomised to receive enemas containing 1 g of 4-ASA or placebo, and 22 to receive 2-gram enemas of 4-ASA or placebo. For each dose of 4-ASA there was clinical and sigmoidoscopic improvement, which reached significance when all patients receiving 4-ASA enemas were compared with those receiving placebo enemas (Cochran's test: p less than 0.005). There was also a trend towards histological improvement, but this failed to reach the level of significance. These findings suggest that 4-ASA may provide a stable, inexpensive alternative to 5-ASA for the topical treatment of ulcerative colitis or for linking to carrier molecules for release in the colon.

Aminosalicylic Acid↗

PubMed1984

Natural killer cells and spontaneous cell-mediated cytotoxicity in the human intestine.

Spontaneous cell-mediated cytotoxicity (SCMC) has been investigated in mononuclear cells (MNC) isolated from intestinal mucosa and autologous peripheral blood from human subjects. The proportion of cells with the NK-K phenotype (Leu 7+) were substantially lower in intestinal MNC than in autologous peripheral blood. SCMC of K-562 target cells when tested at an effector to target (E:T) ratio equivalent to that used for peripheral blood MNC was markedly deficient in intestinal MNC. This was not due to the effect of EDTA and collagenase used in the isolation process. However, at high E:T, ratios, significant cytotoxicity was demonstrated for most intestines examined probably reflecting a low proportion of effector cells within the intestinal MNC population. SCMC in both intestinal and autologous peripheral blood MNC were similarly related to the Leu 7+:T ratios used in the assay indirectly suggesting that the Leu 7+ cell may be responsible for the observed cytotoxicity. It is concluded that the apparent functional difference between similar cells derived from different sites may be largely related to differing proportions of effector cells. The findings indicate the need for specific definition of the effector cell and suggest that intestinal SCMC in health and various disease states requires re-appraisal.

Colon↗

PubMed1984

The mononuclear cells of human mesenteric blood, intestinal mucosa and mesenteric lymph nodes: compartmentalization of NK cells.

The proportions of T cell subsets and Leu 7+ cells and the spontaneous cell-mediated cytotoxicity (SCMC) of isolated mononuclear cells have been determined across the mesenteric vascular bed and along the intestinal mucosal-mesenteric lymph node (MLN) axis in patients undergoing abdominal surgery. Whereas the proportion of T4+ and T8+ cells were similar in simultaneously taken PVB and mesenteric venous blood (MVB), the proportion of Leu 7+ cells was higher in MVB in 16 of 17 studies (15.4 +/- 6.8%, 10.8 +/- 5.1%). Additional studies showed that the proportions of lymphocyte subsets in peripheral arterial blood are the same as those in PVB. Thus, an enrichment of Leu 7+ cells occurs across the mesenteric vascular bed. Isolated intestinal and MLN mononuclear cells contained similarly high proportions of T4+ and T8+ cells as in PVB but Leu 7+ cells made up a minority subpopulation in intestinal (1.3 +/- 0.8%) and MLN mononuclear cells (1.0 +/- 0.9%). The SCMC of intestinal and MLN mononuclear cells was low and paralleled the proportion of Leu 7+ cells. Despite the higher proportions of Leu 7+ cells in MVB, the SCMC was less than that of PVB in eight patients with inflamed intestine and not significantly different from PVB in seven patients with normal intestines. These paradoxical findings were at least in part due to inhibitory factors in mesenteric plasma. In conclusion, NK cells appear to be largely confined within the vascular system and the enrichment of Leu 7+ cells across the mesenteric vascular bed suggests that this compartmentalization may be due to differences in the traffic of lymphocyte subpopulations through the intestinal mucosa and MLN.

Cell Movement↗

PubMed1983

T lymphocyte subsets in inflammatory bowel disease: peripheral blood.

Peripheral blood T lymphocytes and T lymphocyte subsets have been quantified in 28 patients with ulcerative colitis and 26 with Crohn's disease by an indirect immunofluorescence technique using monoclonal antibodies: OKT3, which detects all peripheral blood T lymphocytes; OKT4 (T cells of helper phenotype); and OKT8 (T cells of supressor-cytotoxic phenotype). Eighteen normal subjects and 16 patients with a variety of non-inflammatory gastrointestinal disorders were studied as controls. No significant differences were found between patient and control groups in the proportions of circulating T lymphocytes or their subsets. When compared with normal subjects, absolute numbers of T lymphocytes were reduced in patients with active ulcerative colitis or Crohn's disease (p less than 0.05). OKT4+ T cell numbers were reduced in ulcerative colitis, whether active (p less than 0.02) or inactive (p less than 0.05) and in active Crohn's disease (p less than 0.05) Numbers of OKT8+ T cells were reduced in active Crohn's disease (p less than 0.01). There were no differences in T lymphocyte numbers between the patient groups and the disease control subjects. The OKT4+:OKT8+ ratio in patients with inflammatory bowel disease did not differ from that in controls. No relation was found between any of the parameters studied and disease activity, site, or extent of disease, or treatment with sulphasalazine or corticosteroids. The presence of Ia-like, HLA-DR antigens on T cells was detected using a double marker immunofluorescence technique. In control subjects up to 7% of OKT3+ cells were HLA-DR+. In only three patients was the proportion of HLA-DR+ cells greater than in controls. These results indicate that the pathogenesis of ulcerative colitis or Crohn's disease does not depend upon an alteration in the proportion of circulating T lymphocytes nor upon an imbalance of T lymphocyte subsets as defined by monoclonal antibodies. The reduction in T lymphocyte numbers may result from mucosal infiltration. The findings also suggest that circulating T lymphocytes are not activated.

Adolescent↗

PubMed1983

Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis.

HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phosphatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+/- NSA+/- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+/-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+/- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine. The alterations in inflammatory bowel disease may represent activation in response to an invading antigen.

Colitis, Ulcerative↗

PubMed1983

Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease.

Lymphocyte subpopulations in human small intestinal mucosa have been studied using an immunofluorescence technique on tissue sections. In the normal intestine, the majority of intraepithelial lymphocytes (IEL) were of suppressor-cytotoxic phenotype (HuTLA+ UCHTI+ OKT8+ OKT4-; 84%). Only one-third of these OKT8+IEL reacted with anti-Leu-1, and antibody directed towards a 67,000 dalton antigen found on peripheral blood T cells. IEL failed to express the activation antigen, Tac, and also lacked detectable C3b receptor (C3RTO5-). The remaining T IEL, as well as the predominant lamina propria T lymphocytes (LPL), were OKT4+ OKT8-, helper type T cells. Most of the lamina propria OKT8+ cells were also Leu-1-. In patients with adult coeliac disease, the proportions of OKT8+ and OKT4+ lymphocytes in the epithelium were not altered. However, the proportion of OKT8+ Leu-1+TIEL was significantly increased (56 vs 32%; P less than 0.02). IEL were also HLA-DR-, Tac- and C3RTO5-. The proportion of OKT8+ cells in the lamina propria was slightly, but significantly, increased (40 vs 32%; P less than 0.005). Mucosal findings in treated patients did not differ from normal. Lymphocytes with the phenotype of natural killer cells (HNK-1) were rarely found in normal or diseased mucosa. No alterations in the proportions of circulating T lymphocytes or their subsets were found in patients with coeliac disease. These findings illustrate the heterogeneity of lymphocyte subpopulations in normal and in diseased small intestinal mucosa. The changes found in adult coeliac disease may reflect the increased traffic of IEL into the epithelium.

Adult↗

PubMed1983

Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease.

The expression of HLA-DR and HLA-A,B,C antigens by human colonic epithelium has been examined in tissue sections of patients with inflammatory bowel disease using an immunohistological technique. Colonic epithelial cells from all 21 control subjects with histologically normal colonic mucosa were HLA-DR-. In contrast, in nine of 13 patients with active ulcerative colitis and 11 of 12 with active Crohn's disease the epithelium of involved colonic mucosa was HLA-DR+. HLA-DR antigens were found on the epithelium of only one of six patients with ulcerative colitis in remission and one of three with inactive Crohn's disease. Moreover, these antigens were not present on the epithelium of non-inflamed colonic mucosa in two patients with Crohn's disease in whom adjacent involved mucosa showed strong epithelial reactivity. This difference between patients with active and those with inactive disease is highly significant (P less than 0.005). These findings provide further evidence of the importance of cell-mediated immune mechanisms in the pathogenesis of inflammatory bowel disease.

Colitis, Ulcerative↗

PubMed1983

E rosetting lymphocytes in inflammatory bowel disease. An analysis using monoclonal antibodies.

Lymphocytes rosetting with sheep red blood cells (SRBC) have been quantitated in the peripheral blood of patients with ulcerative colitis (UC) or Crohn's disease (CD) and the results compared with those from healthy control subjects. In contrast with previous studies, normal populations of total (SRBC: lymphocyte, 60:1) and avid (8:1) rosetting lymphocytes were found in the patient groups. Analysis of these cells, using monoclonal antibodies, showed that the proportions of OKT3+, OKT4+ and OKT8+ cells were similar in the two rosetting populations. However, for patients with UC, there was a significant increase in OKT4+ cells in the total rosette forming population when compared with healthy subjects. It is concluded that avid rosette forming cells are unlikely to form a functionally distinct population of T lymphocytes and this population, which is thymosin-dependent, is not deficient in patients with UC or CD.

Adult↗

PubMed1983

Ulcerative colitis and persistent liver dysfunction.

Six hundred and eighty-one patients with ulcerative colitis who attend the outpatient clinic in Oxford have been screened for the presence of persistently abnormal liver function tests. Of the 21 patients (3.0 per cent) found with abnormal liver function 17 (2.4 per cent) were shown by cholangiography to have primary sclerosing cholangitis. The liver biopsies from those patients demonstrated a wide range of histological features and were diagnostic of primary sclerosing cholangitis in only 50 per cent of the patients. When persistently abnormal liver function tests are demonstrated in patients with ulcerative colitis it is likely that primary sclerosing cholangitis will be present (81 per cent of patients in this study), and in order to make a reliable diagnosis it is necessary to perform cholangiography in addition to liver biopsy. A close association with primary sclerosing cholangitis and histocompatibility antigens HLA B8 and DR3 is also reported.

Adolescent↗

PubMed1982

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗