Faecal calprotectin in the assessment of Crohn's disease activity.

BACKGROUND: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. AIM: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. DESIGN: Cross-sectional comparative study. METHODS: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores. RESULTS: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). DISCUSSION: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.

Short report: the effect of misoprostol on the anaemia of NSAID enteropathy.

BACKGROUND: Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. METHODS: We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. RESULTS: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.). CONCLUSION: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.

Push enteroscopy in the investigation of small-intestinal disease.

We report our experience with small-bowel push enteroscopy in 50 patients. The indications for push enteroscopy were: anaemia/occult gastrointestinal bleeding (22 patients); overt gastrointestinal bleeding (17 patients); abnormal small-bowel radiology (8 patients) and miscellaneous (3 patients). In those with undiagnosed gastrointestinal bleeding/anaemia, abnormalities were detected in 24/39 patients (62%): small bowel arteriovenous malformations (AVMs) were detected in 19 (49%), and five (13%) had lesions in the upper gastrointestinal tract. Seventeen patients had heater-probe ablation therapy of vascular lesions: nine patients had small-intestinal lesions, four patients gastric lesions, and four patients combined gastric and small-intestinal lesions. In those with abnormal small-bowel radiology, abnormalities were detected in 6/8 patients. We conclude that (i) push enteroscopy can establish a diagnosis in a high proportion of patients with gastrointestinal bleeding; (ii) heater-probe ablation therapy of vascular lesions can be performed routinely at the time of enteroscopy; (iii) a significant proportion of patients (9/50) referred for enteroscopy with undiagnosed gastrointestinal bleeding have lesions in the stomach/proximal duodenum missed at diagnostic endoscopy. Push enteroscopy is a valuable diagnostic and therapeutic endoscopic procedure.

Measurement of fat absorption using [3H]glycerol triether and [14C]glycerol trioleate in man.

A direct test of lipid absorption has been developed using [3H]glycerol triether as a lipid marker and [14C]glycerol trioleate as the test lipid. Percentage absorption of triolein is calculated from the isotope ratio ingested and excreted in faeces. The test is independent of a complete faecal collection, reproducible and shows little day to day variation. Absorption in 25 normal subjects ranged from 96.4--100% (mean 98.6, S.D. +/- 1.15). In 24 patients with known pancreatic or small intestinal disease and steatorrhoea absorption ranged from 0.01% to 89.9%. The test has also been assessed by comparison with a standard Lundh test and faecal fat estimation in 34 patients.

Magnesium deficiency in patients on home enteral nutrition.

Home enteral nutrition (HEN) is an established method of long term nutritional support. Many patients receiving HEN have Crohn's disease complicated by intestinal failure and malnutrition, including magnesium deficiency. It is unknown if HEN can correct magnesium deficiency or if patients on HEN can become magnesium deficient. We measured total magnesium intake in nine patients receiving HEN, and assessed their magnesium status. Two patients had magnesium intakes below the recommended dietary allowance of 15 mmol/day. Four patients (44%) had biochemical evidence of magnesium deficiency, although no patient had clinical signs of magnesium deficiency. Several magnesium deficient patients used a liquid feed which had a low magnesium content. Patients on HEN should have their magnesium status checked regularly and may require magnesium supplements.

Plasma kinin-precursor levels in clinical intestinal inflammation.

Plasma kinin-precursor (kininogen) concentrations were measured in the peripheral venous blood of 7 untreated patients with inflammatory bowel diseases, 12 healthy subjects, and 5 uncomplicated fracture cases. The mean plasma kininogen levels were significantly raised (P less than 0.025) in patients with intestinal inflammation (7.0 +/- 1.0 micrograms BK Eq/ml), as compared with the value found in healthy subjects (5.7 +/- 0.7 micrograms BK Eq/ml), and in fracture cases (5.0 +/- 1.2 micrograms BK Eq/ml). The packed cell volume did not differ (P greater than 0.05) between patients and control groups. Thus, the raised plasma kininogen levels observed in patients were not the result of nonspecific changes in plasma volume. It is suggested that raised plasma kininogen might be due to increased synthesis to provide substrate for excessive kinin-formation, to a potent inflammatory agent, or to high synthesis of acute-phase reactants. The possible significance of this observation is discussed.

Push enteroscopy.

Push enteroscopy has superseded sonde enteroscopy principally because of its ability to provide therapy, as well as diagnosis. An overtube limits gastric looping and allows deeper jejunal insertion. A working channel allows therapeutic intervention. The technique is increasingly used to the diagnosis and treatment of small intestinal disorders, particularly in obscure gastrointestinal bleeding. The wider acceptance of push enteroscopy into routing practice requires further clinical effectiveness data.

Mg deficiency in chronic inflammatory bowel disease and requirements during intravenous nutrition.

Assessment of magnesium (Mg) status by serum and 24-hr urine estimations has been used to study a group of 17 patients with severe Crohn's disease, 10 of whom have required intravenous (IV) nutrition. Mg depletion was present in 15 (88%) and severe enough to cause symptoms in two. Urine levels were low in most patients and would appear to be a more sensitive indication of Mg depletion than serum levels alone. Serum Mg levels were significantly lower in the Crohn's group than in a group of hospital controls; 5-10 mmol of IV Mg were required daily to prevent Mg depletion during IV nutrition and some patients required higher intakes. Three patients with particularly severe malabsorption required oral Mg supplements in the long-term. The rationale for using our method of assessing Mg status, and the importance of recognizing and treating chronic Mg deficiency are presented.

Asthma leaflets for patients: what do asthma nurses use?

This study investigated patient information leaflets used by trained asthma nurses, and nurses' satisfaction with these. Main outcome measures were frequency of use, sources of material, and rating of reliability and readability. A total of 775 practice nurses with a diploma in asthma working in the general practice setting were surveyed using a postal questionnaire. Forty two percent of questionnaires (326) were returned. The provision of asthma information is an integral part of patient care by the trained asthma nurse. Most nurses (260, 83%) gave out between one and ten leaflets per week. An abundance of diverse information is available from a variety of sources, main sources used were Glaxo-Wellcome (cited by 47% of respondents), National Asthma Campaign (NAC) (19% of respondents) and Astra (19%). Pharmaceutical company material was considered more easily available, free of charge and more attractively presented. NAC material was viewed as more accurate. Assessment of NAC, Glaxo-Wellcome and Astra booklets revealed that they conformed to British Thoracic Society Guidelines for acute asthma. Thus, nurses stated a preference for charity information but in practice used a predominance of pharmaceutical company information. This appears to be because pharmaceutical company information was more readily available and free of charge. Nurses felt unease with self-perceived over-reliance on pharmaceutical company information.

Helicobacter pylori eradication for peptic ulceration: an observational study in a Scottish primary care setting.

Despite being established for the treatment of peptic ulcer (PU) disease, few studies have assessed the long-term effectiveness and economic benefits of Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate the effect of community based Hp eradication for patients with chronic peptic ulcer disease requiring maintenance acid suppression. The endpoints used were the patients dyspeptic symptoms and the requirement for the prescription of maintenance acid suppression therapy. The study area covered seven general practices in the Glasgow area. Patients with previously diagnosed peptic ulcer disease receiving prescribed acid suppression therapy were invited to a dyspepsia clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive patients received Hp eradication therapy and were reviewed six weeks later. At six months a review of practice records was carried out, and two years after eradication a postal questionnaire was sent to participating patients. A total of 243 patients attended the initial clinic of which 81.9% were HRBT positive. 156 of 196 patients offered Hp eradication re-attended at six weeks. The per protocol eradication rate was 91.7%. After six months patients who had received eradication therapy were less likely to require maintenance acid suppression therapy compared with those to whom eradication was not given. Two years after treatment 76.5% of patients felt their symptoms were improved, but 42.2% were still receiving maintenance therapy. The estimated cost of treatment per month per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In conclusion we felt that community based Hp eradication for patients with chronic PU disease is effective, however it does not completely alleviate dyspepsia. Predictors of symptomatic response or of no longer requiring acid suppression therapy after two years were younger age of onset of PU disease and absence of pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication improves patients symptoms, reduces the requirement for maintenance acid suppression and is cost-effective after two years follow-up in this targeted group.

Muscle activity during lifting: examining the effect of core conditioning of multifidus and transversus abdominis.

BACKGROUND: It is well accepted that both multifidus and transversus abdominis muscles have a vital role in maintaining spinal stability. OBJECTIVE: To determine if multifidus and transversus abdominis could be strengthened by a six-week conditioning program and to establish if the amount of electromyographic (EMG) activity in external oblique differed in a lifting and holding task after the conditioning program. METHODS: EMG activity of external oblique during a lifting and holding task was obtained. Multifidus cross-sectional area and transversus abdominis width were measured using real time ultrasound in six males and five females, with no back pain (mean age of 26.3 (± 5.4) years). The participants then performed a six-week muscle-conditioning program for multifidus and transversus abdominis, after which the EMG activity of external oblique and dimensions of multifidus and transversus abdominis were re-measured. RESULTS: Both multifidus and transversus abdominis significantly increased in size. There was significantly less activity in external oblique during a lifting task after the conditioning program, with no change in external oblique activity during a holding task. CONCLUSIONS: this study may indicate a link between the dimensional increase of multifidus and transversus abdominis, and the decrease in EMG activity in external oblique during lifting.

The effect of pH on folic acid absorption in man.

1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease. 2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PTEGlu than normal subjects and patients with treated coeliac disease. 3. The "resting" pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease. 4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects. 5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum.

Small bowel enteroscopy in undiagnosed gastrointestinal blood loss.

Sixty five of 70 consecutive patients with undiagnosed gastrointestinal blood loss were examined using the new technique of small bowel enteroscopy. Using a balloon driven sonde enteroscope (SIF-SW) extended views of the small bowel were obtained as far as the distal ileum. Medium length of small bowel examined was 140 cm (range (30-200 cm). All patients studied had a normal upper gastrointestinal endoscopy. Nineteen (41%) of 46 anaemic rheumatoid arthritis patients taking non-steroidal antiinflammatory drugs (NSAID) and three (27%) of 11 patients with unexplained iron deficiency, were found to have small bowel lesions to account for their anaemia. Small bowel lesions were found in a further three of eight (37%) patients with acute gastrointestinal bleeding. The procedure failed or was terminated in five patients. Small bowel enteroscopy has considerable potential in the investigation of undiagnosed gastrointestinal blood loss and deserves more widespread application.

Pharmacological implications of cellular localization of alpha1-adrenoceptors in native smooth muscle cells.

1. This study examines the cellular localization of alpha1-adrenoceptors and demonstrates that binding to intracellular receptive binding sites in native smooth muscle cells may influence the pharmacological profile of agonists or antagonists. The example tissue studied was rat basilar artery. 2. An alpha1-adrenoceptor antagonist and fluorescent analogue of prazosin, BODIPY-FL prazosin (QAPB) allowed visualization, with high resolution, of both plasma membrane and cytosolic binding sites on live native cells, as previously shown in cells harbouring recombinant receptors. QAPB-associated fluorescence binding was both time- and concentration-dependent in rat basilar smooth muscle cells and affinity for alpha1-adrenoceptors was calculated from specific binding curves as 1.1 nM. 3. Concentration-dependent binding of QAPB detected in smooth muscle cells dissociated from rat basilar arteries was composed of diffuse and clustered fluorescence. Visually the diffuse component of fluorescence was the more evident up to a concentration of 5 nM QAPB. Confocal visualization of an optical section through the cell showed that the clustered component was located mainly intracellularly. In rat basilar artery smooth muscle cells the intracellular binding sites were located in close proximity to the nuclear membrane. 4. 3D models of QAPB-associated fluorescence demonstrate that a high proportion of effective binding sites are intracellular, showing not only that a high proportion of receptors are located inside the cell but also that in this location they can bind ligands. This has implications for pharmacological analysis in relation to the consequences of intracellular binding per se and for differential effects upon the pharmacology of particular ligands according to whether they can enter the cell.

Role of taurocholic acid in production of gastric mucosal damage after ingestion of aspirin.

The possibility that aspirin-induced gastric mucosal damage may occur more readily in the presence of bile has been studied in man using measurement of transmucosal electrical potential difference as a marker of disruption of the gastric mucosal barrier. After the introduction of acetylsalicylic acid (600 mg) in suspension to seven subjects the mean electrical potential difference (plus or minus S.E. of mean) fell significantly from -33-3 plus or minus 2-0 mV to - 17-1 plus or minus 2-1 mV, and after the introduction of taurocholic acid (5 mmol/1) to seven other subjects the electrical potential difference fell significantly from -38-1 plus or minus 3-0 mV to-19-1 plus or minus 3-4 mV, the mean duration of these changes being 14-4 and 17-5 minutes respectively. When a combination of acetylsalicylic acid and taurocholic acid was introduced to eight subjects the mean electrical potential difference also fell significantly from -38-6 plus or minus 1-8 mV to -17-9 plus or minus 1-8 mV, but mean duration of this change (27 minutes) was significantly longer than that found after acetylsalicylic acid or taurocholic acid alone. These results indicate that the ingestion of aspirin, together with coincidental reflux of bile from duodenum, may be a factor in the pathogenesis of aspirin-induced gastric mucosal damage.

The effect of frusemide on water and electrolyte absorption from the human jejunum.

1. Frusemide, in a dose of 120 nmol (40 mg) administered intravenously, significantly reduced the absorption of water and electrolytes from the human jejunum, a double-lumen perfusion system with proixmal occluding balloons being used. Net secretion of water and electrolytes occurred in some subjects. 2. No significant change in water and electrolyte absorption was observed with 60 nmol (20 mg) of frusemide. 3. These findings may explain the diarrhoea which may be induced by fursemide in some patients.

Heterogeneity of endothelin-B receptors in rabbit pulmonary resistance arteries.

We have previously shown that endothelin-B (ETB) receptors mediate contraction in human and rat pulmonary resistance arteries (PRAs). Here we characterize the endothelin (ET) receptors in rabbits PRAs. PRAs (approximately 150 microns i.d.) were studied using wire myography. Vasoconstrictor effects to ET-1, ET-3, and the ETB-selective agonist sarafotoxin S6c (S6c) were studied in the presence and absence of the ETA receptor antagonist FR139317, the ETB-selective antagonist BQ788, and the mixed ETA/ETB antagonist SB209670. The effect of SB209670 was also studied in human PRAs (approximately 250 microns i.d.). Competitive ET-1 binding studies were also carried out on rabbit small pulmonary artery homogenates. The potencies of the agonists were in the following order: S6c > ET-3 = ET-1. Concentration-response curves (CRCs) to ET-1 were biphasic, with a gradual slope up to approximately 1 nM and a steeper component at higher concentrations of ET-1. Neither FR139317 (1 microM) nor BQ788 (1 microM) inhibited responses to ET-1. BQ788 inhibited S6c- and ET-3 induced contractions with pKb values of 6.8 +/- 0.1 and 6.3 +/- 0.2, respectively. SB209670 inhibited responses to ET-1 in the higher concentration component of the CRC and inhibited responses to S6c in a competitive fashion. pKb values for ET-1 and S6c were 6.8 +/- 0.2 and 7.5 +/- 1, respectively. SB209670 (0.1-1 microM) totally abolished responses to ET-1 in human PRAs. The binding assay established two ET binding sites in rabbit PRAs, one low affinity (Ki = 480 pM) and one high affinity (Ki = 64 fM). The study provides evidence for a heterogeneous population of ETB-like receptors in pulmonary resistance arteries, including an atypical ETB receptor sensitive to SB209670.

Enteroscopic diagnosis of small bowel ulceration in patients receiving non-steroidal anti-inflammatory drugs.

15 patients with rheumatoid arthritis who were receiving non-steroidal anti-inflammatory drugs (NSAIDs) and who had chronic occult gastrointestinal bleeding underwent extended small bowel examination with a Sonde enteroscope. 7 patients (47%) were found to have jejunal or ileal ulceration. Small bowel enteroscopy may be a valuable technique for the investigation of undiagnosed gastrointestinal bleeding.

Can 111indium autologous mixed leucocyte scanning accurately assess disease extent and activity in Crohn's disease?

111Indium autologous mixed leucocyte scanning has recently been used for the investigation of Crohn's disease. Nineteen patients had indium scans to assess disease extent and activity. The scans were compared with conventional imaging techniques and indices of disease activity including clinical scores, ESR, CRP, and GI protein loss. In five patients with active disease the scans were negative and overall there was poor correlation between the scan scores and the other indices of disease activity. Indium scanning correctly located extent of disease in only 58% of patients. 111Indium mixed leucocyte scanning may be more suited for the assessment of disease extent and activity in severely ill patients with Crohn's disease.