Can faecal calprotectin predict relapse in inflammatory bowel disease: a mini review.

Crohn's disease and ulcerative colitis are chronic inflammatory disorders affecting the gastrointestinal tract. Faecal calprotectin is a protein complex of the S-100 family of calcium-binding proteins present in inflammatory cells that can be measured in stool samples, which act as a biomarker for bowel inflammation. Elevated faecal calprotectin has been shown to reflect the presence of ongoing mucosal inflammation, which improves with mucosal healing. The aim of this review was to evaluate the available evidence on the ability of faecal calprotectin to predict a relapse in inflammatory bowel disease. Multiple retrospective studies have shown that patients who relapse have significantly higher levels of calprotectin in their stool compared with non-relapsers, especially in ulcerative colitis. Elevated faecal calprotectin postoperatively in Crohn's disease was also shown to be indicative of a relapse. However, the association of a raised faecal calprotectin and relapse is not universal and may be explained by the different patterns of mucosal inflammatory activity that exist. In conclusion, we put forward our hypothesis that changes such as a rise in faecal calprotectin levels may be more predictive of a relapse than absolute values.

Small bowel bacterial overgrowth in symptomatic older people: can it be diagnosed earlier?

BACKGROUND/OBJECTIVES: In older people, small bowel bacterial overgrowth syndrome may be a common, but under-diagnosed, cause of diarrhoea and nutrient malabsorption. We aim to determine which clinical features and baseline laboratory investigations indicate a high likelihood of small bowel bacterial overgrowth as defined by a positive glucose breath test. METHODS: A retrospective analysis of records for all patients referred for glucose breath test over a 6-year period to a teaching hospital. RESULTS: Out of 197 referrals, 168 patient records were located and analysed (62 male, 106 female; median age 65). Patient characteristics predictive of a positive glucose breath test were: increasing age (p < 0.01), low serum vitamin B12 (p = 0.02), low serum albumin (p = 0.03), previous partial gastrectomy (p < 0.01), previous right hemi-colectomy (p < 0.01), presence of small bowel diverticulae (p = 0.01) and concurrent use of a proton pump inhibitor (p < 0.01). 52.5% (n = 21/40) of patients studied who were over 75 years old versus 21.8% (n = 28/128) of those under 75 years old had a positive glucose breath test (p < 0.01). The median time to diagnosis, from first hospital visit to positive glucose breath test, was 39 weeks. CONCLUSIONS: There is often a significant delay in diagnosis of small bowel bacterial overgrowth. We suggest that this diagnosis should be considered earlier in the investigative algorithm in older patients with indicative symptoms and a predisposing factor (including previous partial gastrectomy, previous right hemi-colectomy, small bowel diverticulae or use of a proton pump inhibitor) or concurring laboratory indices (low vitamin B12 or albumin).

Human thiopurine methyltransferase activity varies with red blood cell age.

AIMS: Inherited differences in thiopurine methyltransferase (TPMT) activity are an important factor in the wide interindividual variations observed in the clinical response to thiopurine chemotherapy. The aim of this study was to establish a population range for red blood cell (RBC) TPMT activity in children with acute lymphoblastic leukaemia (ALL) at disease diagnosis. An additional aim was to investigate factors that can influence TPMT activity within the RBC. METHODS: Blood samples were collected from children with ALL at disease diagnosis, prior to any blood transfusions, as part of the nationwide UK MRC ALL97 therapeutic trial. RBC TPMT activity was measured by h.p.l.c. RBCs were age-fractionated on Percoll density gradients. RESULTS: Pretreatment blood samples were received from 570 children within 3 days of venepuncture. TPMT activities at disease diagnosis ranged from 1.6 to 23.6 units/ml RBCs (median 7.9) compared with 0.654-18.8 units (median 12.9), in 111 healthy control children (median difference 4.5 units, 95% CI 3.9, 5.1 units, P < 0.001). A TPMT quality control sample, aliquots of which were assayed in 60 analytical runs over a 12 month period, contained a median of 11.98 units with a CV of 11.6%. Seven children had their RBCs age-fractionated on density gradients. TPMT activities in the top gradient (young cells) ranged from 4.2 to 14.1 units (median 7.5) and in the bottom gradient (old cells) 1.5-12.6 units (median 4.7 units), median difference 2.3 units, 95% CI 0.7, 4.1, P = 0.035. CONCLUSIONS: Circulating RBCs do not constitute a homogeneous population. They have a life span of around 120 days and during that time undergo a progressive ageing process. The anaemia of ALL is due to deficient RBC production. The results of this study indicate that RBC TPMT activities are significantly lower in children with ALL at disease diagnosis. This may be due, at least in part, to a relative excess of older RBCs.

Cervicovaginal foetal fibronectin in the prediction of preterm labour in a low-risk population.

The aim of this study was to evaluate the role of cervicovaginal fibronectin as a screening test in a low-risk population. Swabs were taken from the posterior fornix at 28 weeks gestation and foetal fibronectin levels were assayed using enzyme immunoassay. Eighteen patients (7.7%) delivered at less than 37 weeks of gestation, and 6 (2.4%) at less than 34 weeks of gestation. Five patients (2.1%) had a positive fibronectin test result. The sensitivity, specificity, positive predictive value and negative predictive value in the prediction of delivery less than 37 weeks of gestation were 16.7%, 99.1%, 60.0% and 93.4%, respectively. The sensitivity of foetal fibronectin in the prediction of delivery less than 34 weeks of gestation was higher (50%) compared with the prediction of delivery less than 37 weeks of gestation (16.7%). The low sensitivity of this test suggests a limited role for cervicovaginal fibronectin in the low-risk population. Further studies need to be carried out to assess whether multiple testing of cervicovaginal fibronectin at different gestational ages will further increase the sensitivity.

Suppressor cell function in renal failure and transplant patients.

Suppressor cell function was assessed in 13 patients with chronic renal failure not on dialysis, 10 patients on regular hemodialysis and 11 renal transplant patients by means of the Concanavalin A inducible Suppressor Cell Assay. The mean Suppression Index (S.I.) in the undialysed patients (0.76 +/- 0.39) and those of the dialysed patients (0.72 +/- 0.18) were not significantly different from the 25 healthy controls (0.68 +/- 0.22). However the S.I. in the renal transplant patients (1.11 +/- 0.41) was significantly different from the normal controls as well as the undialysed and dialysed patients. Although there was no correlation between S.I. and age, post transplant follow up period, serum creatinine concentration, prednisolone or azathioprine dosage it is likely that the cause of the impaired suppressor cell function was due to the immunosuppressive agents used.

Epstein-Barr virus specific T-cell response in nasopharyngeal carcinoma patients.

There is a substantial body of evidence suggesting an association between Epstein-Barr virus (EBV) and undifferentiated nasopharyngeal carcinoma (NPC). The present study has compared a group of NPC patients (newly diagnosed and long-term survivors) and controls for EBV-specific T-cell immunity using the regression of transformation assay. Newly diagnosed patients (17 tested) when compared with either long-term survivors (20 tested) or controls (30 tested) showed a significant impairment in virus-specific T-cell immunity (p = 0.036, p = 0.043 respectively). Furthermore, donors with IgA antibody to EBV showed a significant depression in virus-specific T-cell immunity compared with donors without IgA antibody (19 IgA-positive, 48 IgA-negative; p = 0.0025). These results may be important in explaining the postulated role of EBV in the aetiology of NPC.

Loss of concanavalin A induced suppressor T-lymphocyte function in patients with mesangial IgA nephritis.

Using the method of concanavalin A (Con a) inducible suppressor activity the peripheral mononuclear cells (PMC) of 17 patients with Mesangial IgA nephritis, 13 patients with idiopathic mesangial proliferative glomerulonephritis but with no IgA deposits on immunofluorescence (Non-IgA nephritis) and 18 healthy subjects were studied. DNA synthesis was measured by incorporation of 3H Thymidine. The mean suppression index (S.I.) of 0.94 +/- 0.08 (SEM) in the IgA nephritic patients was significantly different from that of the non-IgA nephritic patients (0.67 +/- 0.05) (P less than 0.01) as well as the group of normal healthy controls (0.64 +/- 0.05) (P less than 0.0025). The data show that patients with IgA nephritis have abnormal suppressor cell function and suggest an autoimmune basis in the pathogenesis of IgA nephritis.

General immunological status of nasopharyngeal carcinoma patients in Singapore.

Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole.

Impaired general cell-mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma.

General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vivo Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreated NPC patients also showed lymphocyte hyporesponsiveness to PHA compared to 15 (15.5%) of 97 control patients. Combined deficiencies were observed in 35 (42.2%) of 83 NPC patients compared to only 2 (3.3%) of 61 control patients. No difference in the frequency of immunodeficiency was observed between "early" and "late" disease patients. CMI functions of treated "remission" NPC patients were found to be impaired to the same extent as those of untreated NPC patients.