Biomedical subjects

C S Probert

Publications and source records attributed to C S Probert.

At least 37 records · Page 2Linked to original sources

PubMed1997

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases.

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin-peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their alpha-2,6 or alpha-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy.

Asia, Southeastern↗

PubMed1996

Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease.

It is increasingly recognized that chronic Ag exposure may lead to clonal expansions of T cells, including those within the peripheral blood. Inflammatory bowel disease is a chronic, multisystemic disease of unknown origin that predominantly affects the intestine. We sought to determine whether clonal expansions of T cells are present in the peripheral blood of patients with inflammatory bowel disease by an examination of TCR usage. Positively selected CD4+ and CD8+ peripheral blood T cells were isolated from subjects with active ulcerative colitis, Crohn's disease, and diverticulitis and from normal controls. Analysis of complementarity determining region 3 lengths of 24 TCR-beta chain V region families from CD4+ and CD8+ peripheral blood T cells showed a skewed distribution in the three inflammatory groups, consistent with expansion of T cell clones, in comparison to the normally distributed pattern observed among the control donors. Random sequencing of the PCR amplification products of CD4+ peripheral blood T cells from the subjects with ulcerative colitis, Crohn's disease, and diverticulitis revealed reiterative TCR-beta chain sequences that were not found in the normal donors. In subjects with Crohn's disease, the reiterative TCR-beta chain sequences from the CD4+ peripheral blood T cells were persistent over at least a 1-yr period. The persistently expanded TCR-beta chain sequences of CD4+ peripheral blood T cells were identifiable in genomic DNA isolated from archival tissue of intestine from subjects with Crohn's disease and ulcerative colitis by Southern blotting and direct DNA sequencing. An identical twin pair, concordant for Crohn's disease, shared the same reiterative TCR-beta chain sequences in their CD4+ peripheral blood T cells. These studies show that chronic intestinal inflammation is associated with expansions of CD4+ peripheral blood T cells. Furthermore, in inflammatory bowel disease these T cell clonal expansions are persistent and shared among HLA-identical individuals, implicating a response to specific, persistent, and stimulating Ags in these diseases.

Amino Acid Sequence↗

PubMed1996

A common TCR beta-chain expressed by CD8+ intestinal mucosa T cells in ulcerative colitis.

The human intestine contains two populations of anatomically distinct T cells, intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), both of which preferentially use the TCR-alpha beta. Recent studies of TCR alpha- and beta-chain usage by intestinal intraepithelial lymphocytes, which are predominantly CD8+ T cells, have demonstrated that these cells are oligoclonal in normal intestine. This report examined the TCR beta-chains expressed by purified CD4+ and CD8+ T cells from normal colonic lamina propria and from the intestinal mucosa of patients with active ulcerative colitis (UC). The selective expansion of CD8+ T cell clones, and to a lesser extent CD4+ T cell clones, was observed among both normal LPLs and mucosal T cells in UC. These expanded LPL clones from normal donors were all distinct, but the mucosal T cells isolated from five of nine patients with UC contained CD8+ T cells expressing related V beta 3-J beta 1.6 TCRs. These observations provide evidence for an Ag-specific mucosal T cell response in UC. Further studies will be required to identify this Ag and address whether the T cell response to it plays a primary role in initiating the disease or is secondary to the inflammatory response.

Amino Acid Sequence↗

PubMed1996

Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations and aetiological clues.

We present a review of epidemiological studies of inflammatory bowel disease and abdominal tuberculosis in various migrant communities in the United Kingdom. The differences between various South Asian groups such as Gujaratis, Bangladeshis and Punjabis are discussed in the context of age standardisation of incidence data and various dietary and social activities.

Asia↗

PubMed1996

Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire.

OBJECTIVES: The aims of this study were to (i) estimate the prognosis of a 10-year cohort as expressed by risk of colectomy and risk of development of colorectal cancer, and (ii) assess the impact of long-term sulphasalazine on the natural course of ulcerative colitis. PATIENTS: One hundred and seventy-five patients diagnosed between 1972 and 1981 with either total colitis (n = 143) or with limited ulcerative colitis but deceased (n = 32) were identified. Overall there was 98% case ascertainment and verification. RESULTS: A total of 49 patients underwent a colectomy, 6 as emergency laparotomies, 36 for failed medical management and 7 for known colorectal cancer, giving a crude colectomy rate of 23.2%. The colectomy rate was 7.2% in the year of diagnosis, decreasing in frequency over the next 4 years, then reaching a steady state of approximately 1.7% per year. In the total cohort, colorectal cancer occurred in 10 patients within the study period. The cumulative incidence of colorectal cancer 10 years after diagnosis was 2.1% and at 20 years 7.4% for the total group of patients excluding those with a colectomy. The mean duration of ulcerative colitis before diagnosis was 7.9 years (range 5-12). The crude proportions developing cancer were 5/152 (3%) in the group who took long-term sulphasalazine but 5/16 (31%) in the those who had had their treatment stopped or who did not comply with therapy. This is highly significant using a simple chi 2 test (chi 2 = 20.2, df = 1, P < 0.001). Two methods were used for survival analyses, the log-rank and the generalized Wilcoxon methods. Both give highly significant values for the crude effect of compliance (P < 0.001). CONCLUSION: Patients with ulcerative colitis who were not on long-term sulphasalazine or 5-aminosalicylic acid therapy (either because a doctor stopped it or they did not comply with treatment) were significantly more likely to develop colorectal cancer than their compliant counterparts.

Adult↗

PubMed1996

Over-utilization of the J delta 3 gene-segment in Crohn's disease.

A majority of normal human intestinal intraepithelial lymphocytes (iIEL) are CD8+, express the alpha beta-T cell receptor (TCR) and are oligoclonal. The remainder of normal iIELs, which are also oligoclonal, express the gamma delta-TCR and preferentially utilize variable regions (V delta 1 and V delta 3) which are different from adult peripheral blood lymphocytes (V delta 2). The junctional region usage of gamma delta-TCRs in intestinal diseases is largely unknown. The aim of this study was to examine gamma delta-T cell clonality and junctional region usage of V delta 1 and V delta 3 transcripts in Crohn's Disease (CD) in comparison to several other chronic inflammatory diseases of the colon by polymerase chain reaction amplification, cloning and sequencing. As previously observed in normal subjects, all inflammatory cases examined, including CD (n = 3), ulcerative colitis (n = 1), diverticulitis (n = 1) and lymphocytic colitis (n = 1), the V delta 1 and V delta 3 transcripts contained reiterated sequences consistent with the expansion of gamma delta-T cells expressing these receptors. In 2/3 CD cases, but none of the non-CD inflammatory cases, transcripts containing J delta 3, a rarely used J delta, was observed among the V delta 1 and/or V delta 3 transcripts. Thus, in a subset of CD, gamma delta-T cells expressing J delta 3 may be expanded implicating a role for unique ligands that drive the expansion of T cells expressing these receptors.

Amino Acid Sequence↗

PubMed1995

South Asian and European colitics show characteristic differences in colonic mucus glycoprotein type and turnover.

South Asians in Britain have a high incidence of ulcerative colitis and a low incidence of colorectal cancer. The pattern of mucus production in 12 South Asian and 16 European colitics and a control group of 19 South Asians was studied. Three types of mucin were identified after organ culture of colonic biopsy specimens with a dual label of [3H]-glucosamine and sodium [35S]-sulphate: type A had a high [35S]:[3H] ratio and high incorporation ([3H] dpm/micrograms DNA > 500); type B had a low ratio and high incorporation; and type C had low incorporation but with either high (C1) or low (C2) ratios. European colitic mucins show a significant reduction in the level of sulphation detected by mucin histochemistry with high iron diamine/Alcian blue staining, together with predominantly type B or C2 mucins (low sulphation). South Asian colitics showed histochemically normal patterns of high sulphation and largely type A and C1 mucins (high sulphation). There was no correlation of mucin type with disease activity index in either ethnic group. The appearance of apparently normal mucin in patients with ulcerative colitis may be a useful marker for the identification of a subgroup at low risk of colorectal cancer.

Asia, Southeastern↗

PubMed1995

Some determinants of whole-gut transit time: a population-based study.

Slow whole-gut transit time may be associated with an increased risk of gallstones, and possibly bowel cancer, but its determinants are unknown. We looked for these determinants in a community-based study of 884 women aged 25-69 years and 677 men aged 40-69 years. Transit time was estimated using prospective examination of three stools and a questionnaire about bowel habit. Diet and alcohol intake were assessed using a validated food frequency questionnaire. In women < 50 years not taking oral contraceptives, mean transit time was relatively constant across 10-year age bands (62 to 63 h). In older women it was also relatively constant, but was significantly shorter (58 to 59 h), suggesting an effect of female sex hormones. In women taking oral contraceptives, mean transit-time was 6 h longer than in women of the same age not taking them (95% CI 1.4 to 10.6 h). In men drinking > 40 g alcohol/day, mean transit time was 49 h compared with 54 h in those drinking < 20 g/day (p < 0.0001). In alcohol-abstaining men, an effect of dietary NSP (non-starch polysaccharide or fibre) intake was clearly apparent. Alcohol consumption quickened transit in both sexes; oral contraceptive usage slowed it in women. Body mass index in both sexes, soluble NSP in men, and insoluble NSP in women also significantly and negatively affected transit time. The food groups which were related to transit time were potatoes and cooked fruit in men, and pulses and bread in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Evidence for the ambiguity of the term constipation: the role of irritable bowel syndrome.

A satisfactory definition of constipation is elusive. An important and measurable element is slow colonic transit. Whole gut transit time, a proxy for colonic transit time, can be estimated from self recorded data on stool form and frequency. Our aim was to compare whole gut transit time with subjective definitions in the context of the general population. In a community based sample of 731 women aged 25-69 years the estimated whole gut transit time was compared with two subjective assessments of constipation-the woman's own perception and a symptom based definition proposed by an international working team (Rome definition). We have defined slow whole gut transit time as > 2 SD above the mean in women who seldom passed lumpy stools (that is, > 92 hours). Slow transit was present in 9.3% of the sample. Similar numbers met the subjective definitions (8.5% and 8.2%). However, the overlap between the three definitions was poor. Of 68 women with estimated slow transit, 28 had self perceived constipation, 20 had Rome defined constipation, and only 11 had both. Of subjects classified as constipated by the subjective definitions only 37% had slow transit; they had a high prevalence of irritable bowel symptoms. In conclusion, this study showed that the term constipation is ambiguous and often misleading and that attempts to base a definition on symptoms are misguided. In epidemiological studies, conclusions about the prevalence of constipation should be based on records of stool type and timing.

Adult↗

PubMed1993

Mortality in patients with ulcerative colitis in Leicestershire, 1972-1989. An epidemiological study.

The mortality in 1014 patients with ulcerative proctocolitis diagnosed while resident in Leicestershire identified in a population-based study from 1972 to 1989 was assessed. Ninety-two Europeans and one South Asian died. The standardized mortality ratio (SMR) in South Asians was 26 (95% confidence interval 0-147). In Europeans the overall mortality was not increased, the SMR was 93 (95% confidence interval 75-114). The SMR did not differ between established disease extents, but was highest in those patients in whom the extent was undefined (SMR = 237, 95% confidence interval 130-397). Comparison of SMRs and survival curves showed no difference in mortality in patients diagnosed from 1972 to 1980 and from 1981 to 1989. Mortality was similar in patients who had colectomy and those who had not (SMR = 130, 95% confidence interval 71-219, chi 2(1) = 1.2, NS). Mortality did not change during the study. These findings should be made available to patients and their families.

Adult↗

PubMed1993

Incidence of abdominal tuberculosis in Bangladeshi migrants in east London.

A retrospective epidemiological study of abdominal tuberculosis in a defined population in the London Borough of Tower Hamlets was conducted between January 1985 and 31 December 1989. The total population of 163,900 included a mean of 20,732 Bangladeshis. Of the 13 cases diagnosed 8 were Bangladeshi, with equal involvement of the peritoneum and intestine. The crude incidence in the Bangladeshi community was 7.7 cases/10(5)/year, which was significantly higher than that in Europeans (0.3 cases/10(5)/year, chi 2 with Yate's correction = 14.0 P < 0.001). The highest age-specific incidence was amongst those aged 16-20 years and 41-45 years. Most patients had a laparotomy or peritoneal biopsy to confirm the diagnosis. The response to therapy was good. Only 62% of cases were notified. This study confirms the importance of tuberculosis in the differential diagnosis of abdominal symptoms in Bangladeshi patients.

Adolescent↗

PubMed1993

Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and south Asians in Leicestershire.

The family history of patients identified during incidence studies in Leicestershire were investigated and the prevalence and comparative risks calculated; 1254 patients aged 15 to 80 years were sent a questionnaire about their family history. All cases with a positive family history were reviewed and confirmed cases included in the study. In Europeans the standardised prevalence of Crohn's disease was 75.8/10(5) and that of ulcerative colitis 90.8/10(5). The prevalence of Crohn's disease among South Asians was 33.2/10(5) and that of ulcerative colitis 135/10(5). The prevalence of Crohn's disease in Europeans was significantly greater than that in Hindus (chi 2 = 16, p < 0.001), while the prevalence of ulcerative colitis was significantly lower in Europeans than Hindus (chi 2 = 27, p < 0.001) and Sikhs (chi 2 = 4.4, p < 0.05). The comparative risk of developing ulcerative colitis in first degree relatives of Europeans patients with ulcerative colitis was increased by approximately 15, but the risk of Crohn's disease was not increased. The comparative risk of developing Crohn's disease among first degree relatives of patients with Crohn's disease was increased by up to 35, the comparative risk of ulcerative colitis was approximately 3. The risk among relatives of South Asian patients with Crohn's disease was not increased, but the risk of ulcerative colitis to relatives of patients with ulcerative colitis was. This study supports the view that Crohn's disease and ulcerative colitis arise in people with a genetic predisposition and exposed to some, as yet unknown, environmental factor.

Adolescent↗

PubMed1993

The renaissance of abdominal tuberculosis.

During the last decade, abdominal tuberculosis (TB) has experienced a renaissance. The number of cases diagnosed in Western European and North American countries has dramatically increased. The reasons for this are multiple and include the appearance of AIDS as a significant disorder and the increased morbidity of peoples across the world with the migration of many people from areas of high incidence of TB to the West. Recent epidemiological work is reviewed, and its relationship to these changes considered. The distribution of disease along the gastrointestinal tract and in the mesentery is discussed. The frequency of involvement at various sites and the clinical symptoms caused by the disease are reviewed. The need to diagnose abdominal TB in the 1990s is considered in detail in areas where the disease had previously been thought rare.

Developing Countries↗

PubMed1993

Proctitis and proctosigmoiditis--a need to identify the extent of disease in epidemiological surveys.

Proctitis and proctosigmoiditis may be distinct clinical entities. The lesions are restricted to the rectum or extend proximally to involve the sigmoid colon, respectively. Barium enema examination should be normal proximal to the rectum and sigmoid colon. Histology is used merely to confirm the disease process. We provide evidence drawn from a large epidemiological database that significantly more patients with proctitis than proctosigmoiditis followed over a mean period of 11 years became asymptomatic or had their diagnosis revised to a non-inflammatory bowel disease condition (p < 0.05). The 2 groups were well-matched for age, sex, duration of disease and received similar medical treatment. Future epidemiological studies and therapeutic trials should make a distinction between proctitis and proctosigmoiditis.

Female↗

PubMed1993

British gastroenterologists' care profile for patients with inflammatory bowel disease: the need for a patients' charter.

The follow-up of patients with inflammatory bowel disease (IBD) was investigated using a postal questionnaire sent to 359 members of the British Society of Gastroenterology (BSG), of whom 235 replied. Of patients with IBD, 96% were weighed on each out-patient clinic review and over 60% had their full blood count checked. Although few centres (20%) have computerized recall of their patients for cancer surveillance, 96% did perform such surveillance on patients with ulcerative colitis. The mean duration of disease before surveillance was initiated was 9.6 years. Most clinicians (80%) only surveyed patients with disease extending beyond the transverse colon. Despite recent work on cancer risk age is relatively unimportant to 76% of clinicians in their decision to screen or not. Only 24% of clinicians undertake cancer surveillance in patients with Crohn's disease but these use similar criteria in their selection of patients. Few other tests were performed regularly. Clinic services vary considerably from centre to centre, 62% offer open access to patients with IBD, 8% have a stoma nurse in clinic and 17% a dietitian. Eighty-four per cent of respondents provide educational books and 22% videos. Forty-four per cent of clinicians refer patients for advice to fellow sufferers. We believe there should be a uniform minimum standard of care and services available in clinics throughout the United Kingdom and propose a patients' charter to ensure that this occurs. Such care profiles provide guidelines to those who need to develop standards for resource management.

Adolescent↗

PubMed1993

Disease variations in Asians in Leicester.

The epidemiological study of ethnic groups provides valuable information for physicians in a number of ways. First, it assists in the diagnostic approach in individual patients, especially for doctors unfamiliar with patients of a particular ethnic background. Second, it provides population data to assist in health care planning and provision for the present and future in districts where ethnic minorities are resident in significant numbers. Third, it may provide pointers for the study of pathogenic mechanisms. Fourth, changing epidemiology in migrant ethnic minorities may help to distinguish the degree of influence of genetic and environmental pathogenic factors. These studies are particularly valuable when minority populations are of a size which allows meaningful data to be collected on uncommon conditions. Furthermore the contrasts between migrant and indigenous populations are most clearly seen if migration has occurred over a restricted period. For these and other reasons the study of the migrant population from the Indian subcontinent (defined as India, Pakistan and Bangladesh) which has settled in Leicester since the mid-1960s has proved particularly rewarding. This report summarizes the distinctive epidemiological features of these people now living in Leicester.

Adult↗

PubMed1992

Stoma anxieties: a comparison of the attitudes of Asian migrants and the indigenous population in the United Kingdom towards abdominal surgery and the role of intestinal stomas.

We have studied stoma care nurses' experience with Asian patients having a stoma. The general public's attitudes to abdominal surgery in general were assessed in a survey of employees in Leicester. Many stoma care nurses are aware of the needs of Asian patients, especially with regards to ethnic dress, but only half of the ostomists who wanted to see a stoma care nurse or fellow ostomist were able to do so (chi 2 = 4.5, p less than 0.03). All ostomists considered counselling on education, employment and marriage inadequate. There is a high level of anxiety about stomas and these anxieties are surprisingly similar for all ethnic groups.

Abdomen↗

PubMed1992

The attitude of employers to people with inflammatory bowel disease.

Many patients with inflammatory bowel disease are anxious about their future prospects of employment. Personnel managers at 61 major national and 136 principal local employers in Leicester and Cardiff were asked to provide details about their attitude to people with inflammatory bowel disease and the type of health care they offer to employees. Over one million people were employed by these companies. A poor response rate of 27% suggested at best disinterest in the subject on the part of employers. In those who did reply the attitude to people with inflammatory bowel disease was often positive, although up to a quarter (25%) would not continue to employ people if they developed these conditions and many (30%) would not provide time off work to attend hospital clinics. Only 60% of respondents would consider providing lighter duties to affected employees. In general there is a surprisingly negative attitude to promotion of people with chronic diseases such as epilepsy, multiple sclerosis or liver disease. This seems less so in inflammatory bowel disease.

Attitude to Health↗