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peer-reviewed Faecal VOCs (volatile organic compounds) were compared in horses and ponies before and after 6 weeks on Spring pasture and with and without a dietary supplement (ERME). The supplement was derived from malted barley and contained enzymes which degrade complex carbohydrates, including amylase, maltase, glucanases and fructanases. VOCs of faecal samples were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and the results showed that the faecal microbiome was altered in different ways both by feeding on Spring pasture and by the dietary supplement. The composition of the equine gut microbiome (EGM) is therefore potentially a reflection of dietary constituents, both pasture and supplements; any metabolomic approach should take this into account since the EGM may have modulating effects on physiological parameters such as diabetes and obesity.

Beetroot juice (BJ), a source of nitrate, was added to the diet of thoroughbred racehorses for a four-week period. Analysis of nitrate/nitrite in plasma showed no significant differences between control and dosed groups. SIFT/MS (selected ion-flow tube/mass spectrometry) was used to analyse the faecal metabolome. The levels and types of volatile organic compounds (VOCs) were compared using headspace sampling of faeces from control and beetroot-supplemented equines, However, there were no significant differences apart from raised levels of acetonitrile in samples from the animals dosed with BJ. The conclusion was that racehorses appear not to have nitrate transporters and that addition of BJ to equine diets would not improve performance

Immune Thrombocytopenia is an organ specific autoimmune disorder. It was believed that food intolerance may be a factor in ITP, affecting platelet count. This study investigated whether dietary modification could lead to an increase in platelet count in patients with ITP. IgE and IgG tests were conducted along with platelet counts to see if the role of food in ITP could be better understood. This study found that dietary modification did not affect platelet count in ITP patients. This suggests food intolerance does not cause chronic ITP.

The developed world has seen an alarming increase in the incidence of gastrointestinal diseases, among the most common of which is Crohn’s disease (CD) in the young. The current “gold standard” techniques for diagnosis are often costly, time consuming, inefficient, invasive, and offer poor sensitivities and specificities. This paper compares the performances of three hyphenated instrumental techniques that have been suggested as rapid methods for the non‐invasive diagnosis of CD from urine. These techniques are gas chromatography‐mass spectrometry (GC‐MS), high performance liquid chromatography‐mass spectrometry (HPLC‐MS) and selected ion flow tube mass spectrometry (SIFT‐MS). Each of these techniques is followed by multivariate classification to provide a diagnosis based on the acquired data. The most promising results for potentially diagnosing CD was via HPLC‐MS. An overall classification accuracy of 73% (74% specificity; 73% sensitivity) was achieved for differentiating CD from healthy controls, statistically significant at 95% confidence.

Summary Background It is possible to control Crohn's disease by dietary therapy involving the detection and exclusion from the patient's diet of foods which provoke symptoms. The effects of such treatment on pregnancy have not been studied in detail. Aim To determine the outcomes and complications in pregnancies occurring in women with Crohn's disease receiving dietary therapy. Methods A review by retrospective questionnaire and the contemporaneous medical and dietetic notes over a period of five years of women attending the department of gastroenterology at Addenbrookes hospital, Cambridge for treatment of Crohn's disease by diet. Results Forty seven pregnancies occurred in thirty four women. At conception, 51% of women were in remission, 40% had mildly active disease and 9% active disease. During pregnancy 78% remained stable or improved. Delivery was by caesarean section in 25%. The incidence of miscarriage (21%), stillbirths (2%), congenital abnormality (0%), prematurity (10%) and low birth weight (5%) were not different from those expected in the general population. Food intolerances improved during pregnancy in 66%. Nevertheless 55% relapsed within 3 months post-partum. Conclusions The incidence of complications of pregnancy was no greater than those observed in the healthy British population. Dietary treatment in pregnancy appears to be safe but relapse after delivery is common.

Gastrointestinal diseases such as irritable bowel syndrome, Crohn’s disease (CD) and ulcerative colitis are a growing concern in the developed world. Current techniques for diagnosis are often costly, time consuming, inefficient, of great discomfort to the patient, and offer poor sensitivities and specificities. This paper describes the development and evaluation of a new methodology for the non-invasive diagnosis of such diseases using a combination of gas chromatography mass spectrometry (GC–MS) and chemometrics. Several potential sample matrices were tested: blood, breath, faeces and urine. Faecal samples provided the only statistically significant results, providing discrimination between CD and healthy controls with an overall classification accuracy of 85 % (78 % specificity; 93 % sensitivity). Differentiating CD from other diseases proved more challenging, with overall classification accuracy dropping to 79 % (83 % specificity; 68 % sensitivity). This diagnostic performance compares well with the gold standard technique of colonoscopy, suggesting that GC–MS may have potential as a non-invasive screening tool.

Background: The aim of this study was to determine whether volatile organic compounds (VOCs) present in the headspace of feces could be used to diagnose or distinguish between chronic diseases of the gastrointestinal tract and apparently healthy volunteers. Methods: A total of 87 people were recruited, divided between 4 categories: healthy volunteers (n = 19), Crohn's disease (n = 22), ulcerative colitis (n = 20), and irritable bowel syndrome (n = 26). They each supplied fecal samples before, and except for the healthy volunteers, after treatment. Fecal samples were incubated in a sample bag with added purified air at 40[degrees]C and headspace samples were taken and concentrated on thermal sorption tubes. Gas chromatography-mass spectrometry then desorbed and analyzed these. The concentrations of a selection of high-abundance compounds were determined and assessed for differences in concentration between the groups. Results: Crohn's disease samples showed significant elevations in the concentrations of ester and alcohol derivates of short-chain fatty acids and indole compared with the other groups; indole and phenol were elevated in ulcerative colitis and irritable bowel syndrome but not at a statistically significant level. After treatment, the levels of many of the VOCs were significantly reduced and were more similar to those concentrations in healthy controls. Conclusions: The abundance of a number of VOCs in feces differs markedly between Crohn's disease and other gastrointestinal conditions. Following treatment, the VOC profile is altered to more closely resemble that of healthy volunteers.

© 2013 Bentham Science Publishers.SIFT-MS is used for the first time in profiling the volatile organic profile in faecal headspace in two groups of horses admitted to an equine hospital, one group with acute intestinal disease (colic) affecting the large colon, plus a control group of similarly managed horses admitted for non-gastrointestinal/metabolic reasons (e.g. acute orthopaedic injury). Compounds in faecal headspace which show statistically significant concentration differences between the groups are acetone and methanol. In addition, some ions at various m/z values show significantly different ion counts between the groups. Further information may be gleaned by using multivariate statistics in evaluating the differences between the two horse groups. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were evaluated for reducing the dimensionality of the SIFT-MS data, and OPLS-DA was found to be best at discriminating between the groups, particularly with SIFT-MS data acquired using the H3O+ precursor ion. Analysis of these data also show the significance of ammonia as a discriminating ion. These results show that SIFT-MS may potentially be used on the headspace of horse faecal samples for detecting altered microbial fermentation associated with acute intestinal disease of the colon.

The interactions between disease processes and the metabolism of therapeutic drugs have not been systematically investigated. Inflammation, with the presence of pro-inflammatory cytokines, affects Phase 1 metabolism, particularly the activity of the CYP isoforms. Inflammatory factors also alter the activity of some Phase 2 enzymes, particularly the sulphotransferases (SULT isoforms) responsible for drug sulphonation and the enzyme pathway involved in the supply of sulphate for this reaction. Being ill may, therefore, in itself make drug metabolism unpredictable.

ITP is an organ-specific autoimmune disorder characterised by a low platelet count whose cause is uncertain. A possible factor is food intolerance, although much of the information linking this with ITP is anecdotal. The role of food intolerance in ITP was studied by replacing a normal diet with an elemental diet (E028), but this did not increase platelet counts. Clear differences, however, were apparent between the volatile organic compounds (VOCs) in the urine headspace of patients with ITP and those present in healthy volunteers, which leads to speculation that abnormal metabolic activity of the intestinal microbiome may be a factor causing ITP. However, further work is needed to confirm this. There were also differences between the VOCs of patients on a normal diet and those on the elemental diet, and in this case, the VOCs involved are very likely to be of bacterial origin, as their production is affected by dietary manipulation. Many of these VOCs are known to be toxic.

Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue infection which is rapidly fatal unless diagnosed promptly and treated with immediate debridement of necrotic tissue. As early clinical suspicion is paramount to improved survival, this review aims to increase awareness of the condition.

Reports that bacteria within the Firmicutes phylum, especially the species Faecalibacterium prausnitzii, are less abundant in Crohn's disease (CD) patients and supernatants from cultures of this bacterium are anti-inflammatory prompted the investigation of the possible correlations between the abundance of F. prausnitzii and the response to treatment in patients with gut diseases and healthy controls. In a randomized, double-blind trial, faeces were collected from healthy volunteers, and from patients with active CD, ulcerative colitis (UC) and irritable bowel syndrome before and after treatment. The levels of F. prausnitzii DNA in faecal suspensions were determined by PCR. Treatment by an elemental diet was effective, resulting in decreases in both the Harvey and Bradshaw index (P

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT.

The effects of probiotic supplementation on the intestinal re-growth microbiota following antibiotic therapy were studied in a double-blind placebo-controlled study. In the placebo group, numbers of facultative anaerobes and enterobacteria increased significantly, and at day 35 the numbers were significantly higher in the placebo group than in the active group; in the active group, the numbers of bacteroides increased significantly. Although the numbers of enterococci in both groups did not change, in the placebo group the number of patients harbouring antibiotic-resistant enterococci post therapy increased significantly. There was no change in the incidence rate of antibiotic resistance among the patients in the probiotic group.

Objective An inappropriate mucosal immune response to the commensal bacterial flora may play a role in the pathogenesis of inflammatory bowel disease (IBD). In this study we determined the percentage of immunoglobulin-coated bacteria in the stools of patients and controls.Methods Faecal samples were obtained from 18 patients with IBD (one sample during exacerbation and one shortly after remission was achieved), 15 healthy volunteers, eight infectious colitis patients, and 13 IBD patients in long-term remission. Bacterial immunoglobulin coating was determined by flow-cytometry analysis. Faecal alpha-1-antitrypsin concentrations were determined by radial immune diffusion.Results IBD patients had 69 +/- 19% immunoglobulin A (IgA)-, 56 +/- 32% immunoglobulin G (IgG)- and 56 +/- 29% immunoglobulin M (IgM)-coated bacteria in their faeces. Healthy controls had less immunoglobulin coating, respectively 36 +/- 12%, 11 +/- 4% and 11 +/- 7%. Infectious colitis patients had 57 +/- 14% IgA, 31 +/- 13% IgG, and 42 +/- 16% IgM; however, they had higher faecal alpha-antitrypsin concentrations than IBD patients. Shortly after remission, IBD patients had 65 +/- 20% IgA, 32 +/- 18% IgG and 40 +/- 21% IgM. Long-term-remission IBD patients had normal IgG and IgM but increased IgA (50 +/- 16%) coating.Conclusions Compared with healthy controls, patients with IBD had an increased percentage of immunoglobulin-coated faecal anaerobic bacteria, both in active disease and shortly after remission. These results support the concept that there may be a breakdown of mucosal tolerance to the commensal gut flora in IBD.

Objective Although most causes of abdominal pain have a visceral origin, the musculoskeletal system must be considered when the cause is not obvious. This prospective study aimed to identify questions that would aid the diagnosis of patients with abdominal pain of musculoskeletal origin. Design Assessment of consecutive patients with abdominal pain recruited from gastroenterological outpatient clinics to develop diagnostic pointers to identify abdominal pain arising from musculoskeletal disorders. Participants Subjects with benign abdominal pain, with or without a change in bowel habit, were recruited from gastroenterological clinics. Patients with inflammatory or neoplastic disease were excluded. Setting The study was conducted in the Physiotherapy Department, Addenbrooke's NHS Trust Hospital, Cambridge. Main outcome measures A set of questions developed to indicate a musculoskeletal cause of a patient's abdominal symptoms. RESULTS The questions 'Does taking a deep breath aggravate your symptoms?' and 'Does twisting your back aggravate your symptoms?' had a significant positive indication of abdominal symptoms of musculoskeletal origin. The questions 'Has there been any change in bowel habit since onset of your symptoms?', 'Does eating foods aggravate your symptoms?' and 'Has there been any weight change since onset of symptoms?' had a significant negative indication for abdominal symptoms not of musculoskeletal origin. A combination of these questions gave 96% specificity and 67% sensitivity. Conclusion These questions may help with the early identification of patients with abdominal pain of musculoskeletal origin and will be tested in further studies.

Objective : to determine whether it is possible to separate cases of irritable bowel syndrome associated with excess total hydrogen production (as a surrogate of colonic fermentation; these patients may be offered an exclusion diet as treatment) from other causes of irritable bowel syndrome by determining the amount of hydrogen excreted on patients' breath after oral administration of lactulose. Design : comparison of 24-hour hydrogen excretion and breath hydrogen following lactulose in untreated patients fulfilling the Rome criteria for irritable bowel syndrome, normal controls and irritable bowel syndrome patients who had previously failed to improve on an exclusion diet. Methods : colonic fermentation was measured by indirect calorimetry over 24 h. Immediately after calorimetry, the patients who were fasting received 20 g lactulose; end-expiratory breath samples were then collected every 30 min for 3 h. Hydrogen concentrations were determined by an electro-chemical cell. Results : the total 24-hour excretion of hydrogen was significantly greater in the irritable bowel syndrome group (median 333.7 ml/24 h, interquartile range 234.7-445.67) compared to the normal volunteers (median 203.1 ml/24 h, interquartile range 131.4-256;P = 0.002) or the failed-diet group (median 204.5 ml/24 h, interquartile range 111.35-289.13;P = 0.015). No difference was detected in breath excretion of hydrogen following lactulose in any group. Conclusion : total hydrogen production over 24 h is increased in some patients with irritable bowel syndrome who may respond to exclusion diets. However, this sub-group of patients cannot be identified by measuring breath-hydrogen excretion after lactulose.

Summary Background : Essential fatty acid supplementation has been found to ameliorate certain chronic inflammatory diseases. This effect is thought to be mediated through the modulation of eicosanoid synthesis. Pro-inflammatory eicosanoids have been implicated in ulcerative colitis. Aim : To investigate the possible therapeutic benefit of essential fatty acids in quiescent ulcerative colitis to reduce the frequency of disease relapse. Methods : A randomized, double-blind, placebo-controlled study was performed with a treatment duration of 12 months. Patients with quiescent disease received either trial medication (gamma-linolenic acid, 1.6 g, eicosapentaenoic acid, 270 mg, and docosahexaenoic acid, 45 mg, per day) or placebo (sunflower oil, 500 mg/day). The primary end-point was disease activity, assessed by a previously validated clinical index, sigmoidoscopic appearance and histology. Results : Sixty-three patients were randomized, 31 to receive essential fatty acid treatment and 32 to receive placebo. Disease relapse rates were similar at 12 months (placebo, 38%; essential fatty acids, 55%), as were changes in sigmoidoscopic grade from baseline. Conclusions : The supplementation of the diet with this combination of essential fatty acids does not prolong the period of disease remission of ulcerative colitis.

A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome (IBS). The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria. This study was designed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation. We conducted a double-blind, placebo-controlled, cross-over, four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS. Symptoms were assessed daily by a validated composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose. On placebo, the median symptom score was 8.5 [6.25–11.25 interquartile range (IQR)], the median maximum rate of gas production was 0.55 ml/min (0.4–1.1 IQR), and the median hydrogen production was 189.7 ml/24 hr (118.3–291.1 IQR). On Lactobacillus plantarum 299V the median symptom score was 8 (6.75–13.5 IQR), the median maximum rate of gas production 0.92 ml/min (0.45–1.5 IQR), and the median hydrogen production 208.2 ml/24 hr (146–350.9 IQR). There was no significant difference. Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P = 0.019). In conclusion, Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome.

OBJECTIVES To determine if confirmation of hypolactasia offers any benefit to the dietary treatment of patients with irritable bowel syndrome (IBS). METHODS One hundred and twenty-two consecutive IBS patients (37 male, 85 female) were given lactose hydrogen breath tests (LHBT). Those with positive LHBT followed a low lactose diet for 3 weeks. Those improving on the diet were given double-blind, placebo-controlled challenges (DBPCC) with 5 g, 10 g and 15 g of lactose and a placebo, to confirm lactose intolerance. Those who did not respond to the low lactose diet followed either an exclusion or low fibre diet. Symptoms scores were kept prior to the LHBT, 8 h post-LHBT and daily whilst following any dietary change. Patients with negative LHBT returned to clinic and subsequent dietary interventions were recorded. RESULTS LHBT was positive in 33/122 (27%) IBS patients. Syrr otom scores prior to LHBT were not significantly different between the two groups, but after LHBT the symptoms in the positive group were significantly worse. Twenty-three patients followed a low-lactose diet of which only nine (39%) improved. Six who did not improve followed an exclusion diet, three improved and all were intolerant of milk. Three tried a low fibre diet with two improving. DBPCC were inconclusive. In the negative LHBT group 35 agreed to try a diet and 24 improved (69%). Eight were intolerant of cow's milk. CONCLUSIONS Use of a low lactose diet was disappointing in IBS patients with lactose malabsorption. Food intolerance was demonstrated in IBS patients with positive or negative LHBT and milk was identified as a problem in both groups. DBPCC were inconclusive. There appears to be little advantage in trying to separate patients who malabsorb lactose from others with IBS.

Objective To determine the effect of a specialist nurse on the management outcome of patients with inflammatory bowel disease (IBD). Design Audit of the management of a cohort of patients in the year prior to the employment of the specialist nurse and the year immediately after. Subjects 339 patients, both male and female, with either Crohn's disease or ulcerative colitis, resident in the Cambridge health district. Setting Addenbrooke's Hospital NHS Trust Outpatient Centre. Main outcome measures Health status was measured by blood tests (C-reactive protein, albumin and haemoglobin) throughout the year, symptom indices, number of clinic attendances, admissions to hospital and length of stay. Quality of life was measured via a postal questionnaire. Results Hospital visits were reduced from 1377 to 853 (38% reduction) and in-patient length of stay measured in bed-days from 516 to 417 (19% reduction). The number of patients in remission increased from 63 to 69%. Patient satisfaction improved in key areas, in particular, access to information on IBD and advice on avoidance of illness and maintaining health. Of a total of 251 calls to the telephone helpline, only 19 patients were referred for a medical opinion and five patients required hospital admission. Conclusion The IBD nurse specialist is a valuable and cost-effective member of the gastroenterology team.

Sucrose polyester (SPE) is a tasteless, odourless substance which reduces plasma cholesterolconcentrations and may therefore be valuable as a fat substitute in human foodstuffs. It hasrecently been approved for use in snack foods by the United States Federal Drug Administration.The current study was designed to investigate its effects on gastrointestinal physiology andnutrient absorption in human subjects. A 6-month (2×3-month periods) double-blind, placebo-controlled, randomized, cross-over trial of SPE and control fat was performed in healthy free-living volunteers. Subjects consumed 20–40g of SPE daily (mean 26.8(se6.8) g) which reducedthe intake of total and saturated fat but had no effect on energy intake or body weight. Plasmacholesterol and triacylglycerols were reduced. The frequency of bowel movements and theirurgency were increased and anal leakage occured in 7.2% of subjects. Abdominal pain was morefrequent in subjects receiving SPE and was significantly greater than in the control group after 8weeks feeding. The plasma concentrations of vitamin E and six carotenoids were significantlyreduced. Routine haematology and biochemistry, other vitamins, intestinal biopsies, bile-saltretention, rectal prostaglandins, fractional Ca absorption and aminopyrine metabolism wereunaffected. The ingestion of foods containing 20–40g SPE daily provoked significant gastro-intestinal problems. This intake is greater than that to be expected from the use of SPE in savourysnack foods, for which it has been approved by the United States Federal Drug Administration.However, the favourable effects on lipid profiles must be balanced against the reduction in theconcentrations of vitamins and carotenoids, as these compounds may have beneficial effects onhealth through protection from free-radical oxidative stress.Sucrose polyester: Absorption: Cholesterol

Background: A 30-year-old woman with celiac sprue had progressive weight loss, myalgia, limb-girdle weakness, and dysphagia. Methods and Results: Barium swallow showed an atonic esophagus, and scintigraphic study confirmed esophageal dysmotility. Skeletal muscle biopsy showed characteristic appearances of acid maltase deficiency, which was confirmed by a reduction of leukocyte acid α-glucosidase activity. Conclusions: Nutritional factors may have accelerated the presentation of the lysosomal storage disorder. This is the first reported case of dysphagia caused by esophageal motor weakness in acid maltase deficiency. (Journal of Parenteral and Enteral Nutrition21:046-049, 1997)

The relative abundance of different groups of sulphate-reducing bacteria (SRB) in faecal DNA collected before and after therapy from patients suffering from Crohn's disease (CD), irritable bowel syndrome (IBS) or ulcerative colitis (UC) has been compared with that from healthy controls. Growth tests revealed that SRB were not more abundant in samples from patients with CD before treatment than in the healthy control group. For most of the 128 samples available, these preliminary results were confirmed using degenerate PCR primers that amplify the dsrAB gene. However, some samples from patients with CD before treatment contained a growth inhibitor that was absent from IBS or UC samples. In-depth sequencing of PCR-generated dsrB fragments revealed that the diversity detected was surprisingly low, with only eight strains of SRB and the sulphite-reducing bacterium, Bilophila wadsworthia, detected above the 0.1% threshold. The proportion of the two major species detected, B. wadsworthia and Desulfovibrio piger, was as high as 93.5% of the total SRB population in the healthy control group and lower in all patient groups. Four previously undescribed species were found: it is impossible to predict whether they are sulphate or sulphite-reducing bacteria.

The treatment of irritable bowel syndrome (IBS) remains unsatisfactory. There are no objective markers for diagnosis, and classification (currently based on symptoms) provides little insight into potential causes or optimal therapy. The aim of this study was to determine whether a Swedish classification of IBS based on cluster analysis of patients' symptoms might provide a guide to successful treatment.Patients in a research clinic for IBS were classified according to criteria published by RagnarssonBodemar (RB) and also assessed independently by a clinician. Patients fulfilling the RB criteria for subgroups 1 and 2 received specific treatments, either bulk laxatives or dietary treatment to reduce colonic fermentation, respectively. Patients who did not fit into these categories were given "best treatment" targeted at their predominant symptoms, but not limited in any way. Results before and after follow-up were assessed using a validated symptom-scoring scale.Seventy-one successive patients were recruited, and the numbers falling into RB subgroups 1 and 2 were 15 (21%), and 28 (39%), respectively, leaving 28 (39%) unclassified. Receiver operating characteristic plots showed that the criteria for separation into subgroups 1 and 2 correlated well with the clinician's assessment. After treatment, symptom scores for the whole group showed a significant improvement (p0.0001), but results were significantly better in subgroups 1 and 2 than in those unclassified, even when allowance was made for a potential therapeutic placebo effect of 40%.The RB classification provides a helpful guide to treatment in many cases of IBS.

Recent developments in our knowledge of inflammatory bowel disease (IBD) have been dramatically exciting, but the speed and diversity of progress may seem bewildering. A forthcoming conference on IBD, in association with the British Journal of Hospital Medicine (see p. 351 or www.mahealthcareevents.co.uk/ for full details), provides an opportunity to reflect on the significance of new findings in the pathophysiology of these disorders and ways of improving disease management.

Abnormal fermentation may be an important factor in irritable bowel syndrome (IBS). Gastroenteritis or antibiotic therapy may damage the colonic microflora, leading to increased fermentation and the accumulation of gas. Gas excretion may be measured by whole-body calorimetry but there has only been one such study on IBS to date. We aimed to assess the relationship between IBS symptoms and fermentation rates in IBS. A purpose-built, 1.4-m3, whole-body calorimeter was used to assess excretion of H2 and CH4 in IBS subjects while consuming a standard diet and, again, after open randomization on either the standard diet together with the antibiotic metronidazole or a fiber-free diet to reduce fermentation. Metronidazole significantly reduced the 24-hr excretion of hydrogen (median value compared to the control group, 397 vs 230 ml/24 hr) and total gas (H2 + CH4; 671 vs 422 ml/min) and the maximum rate of gas excretion (1.6 vs 0.8 ml/min), as did a no-fiber polymeric diet (hydrogen, 418 vs 176 ml/min; total gas, 564 vs 205 ml/min; maximum rate of gas excretion, 1.35 vs 0.45 ml/min), with a significant improvement in abdominal symptoms. IBS may be associated with rapid excretion of gaseous products of fermentation, whose reduction may improve symptoms.

In this pilot-scale, double-blind, placebo-controlled trial, 30 patients with Helicobacter pylori infection were randomised into three groups prior to their 7 days eradication therapy, to study the effects of probiotic supplement comprising Lactobacillus acidophilus and Bifidobacterium bifidum on the intestinal microflora in response to antibiotic therapy. Group I received the placebo product from day 1 to day 15, Group II received placebo from day 1 to day 7 and probiotics from day 8 to day 15 and Group III received probiotics from day 1 to day 15. Patients provided stool samples for analysis on days 1, 7, 12, 17 and 27. For patients in Groups I and II, significant increases in the facultative anaerobe component of the microflora occurred between days 1 and 7. In Group I, the numbers remained elevated to day 27 but in Group II, the numbers decreased significantly between days 7 and 27 back to the starting levels. In Group III, the facultative anaerobe population remained stable throughout. The total anaerobe numbers increased significantly at day 27 than at day 1 for Group I, were unchanged throughout for Group II and decreased significantly for the patients in Group III between days 1 and 7 before reverting to the starting levels by day 27. From these results, it can be seen that probiotic supplementation modulates the response of the intestinal microflora to the effects of antibiotic therapy.

Background: Crohn's disease of the esophagus is rare, and medical treatment often ineffective. Complications such as abscess and fistula may arise, and the morbidity of surgery is high. Methods: Two cases of refractory esophageal Crohn's disease were confirmed by endoscopy and biopsy. Percutaneous endoscopic gastrostomies (PEGs) were inserted and used for enteral nutrition for 9 and 1 month, respectively. Results: The PEGs were well tolerated. Symptoms subsided rapidly, and later gastroscopies confirmed healing of the esophageal ulcers. No complications occurred, and the gastrostomy sites closed quickly after removal of the tubes, with minimal scarring. Conclusions: Enteral feeding via PEG appears to be safe and well tolerated and may be of great value in the management not only of esophageal Crohn's disease but also of refractory disease at other sites. (Journal of Parenteral and Enteral Nutrition24:176-179, 2000)

TO THE EDITOR: Psychiatric symptoms occur in approximately 25% of patients receiving corticosteroid therapy with up to 6% of patients experiencing severe complications including psychosis, affective disorders (depression or mania) or delirium (1). In addition, there is increasing evidence of an association between high corticosteroid levels and cognitive impairment (2). Given the frequent use of these drugs, the research literature remains remarkably undeveloped, and data regarding risk factors, etiological mechanisms, and management strategies are scarce. Although patients are frequently well informed about physical side effects, psychiatric side effects receive less attention. Here, we describe the case of a patient with Crohn's disease who developed a steroid-related psychosis, with near fatal consequences.

Rofecoxib and cytomegalovirus in acute flare-up of ulcerative colitis: coprecipitants or coincidence?

Introduction As one of the possible causes of inflammatory bowel disease (IBD), the microbiota in the human gut has been widely studied. Sulphate-reducing bacteria (SRB) have long been considered as candidate pathogens because their metabolic product, sulphide, through its toxic properties, damages the colonic epithelium. However, no specific SRB has been identified as a pathogen to IBD, and even their abundance in the human gut remains controversial. This project compares the amount of faecal SRB in healthy subjects with that in patients either with Crohn's disease (CD) or ulcerative colitis (UC), and traces the change, if any, after treatment in each patient. Methods Faecal samples were collected from 18 healthy subjects, 18 CD patients and 14 UC patients. CD patients were treated with elemental diet and UC patients received conventional treatment. A suspension of the faecal matter from each patient both before and after treatment was inoculated into a sulphate-rich growth medium, Postgate B. The abundance of SRB was gauged according to the amount of black precipitate (ferrous sulphide) formed by SRB. Results Contrary to expectation 88% of healthy subjects carry SRB that produce high levels of sulphide in vitro, despite its cytotoxicity in vivo. In contrast, this carriage rate is low (45%) in CD patients at their initial presentation. After taking elemental diet, the carriage rate of active SRB did not change despite a significant fall in the total amount of gut bacteria. In UC patients, who are often characterised with mucus depletion, the carriage rate of active SRB is significantly lower (31%, p

Background Crohn's disease (CD) and multiple sclerosis (MS) share common pathogenic processes. Interferon (IFN) beta-1a is effective and generally well tolerated in patients with MS and has been shown to down-regulate the expression of interleukin-12, a cytokine that is thought to be involved in mucosal degeneration in CD. IFN beta-1a therefore offers promise as a treatment for CD. Methods In this multicentre, double-blind, placebo-controlled, phase II, dose-finding study, patients with steroid-induced clinical remissions of CD were randomized 1:1:1:1 to subcutaneous IFN beta-1a: 66 mcg three times weekly (tiw), 44 mcg tiw, 44 mcg twice weekly (biw), or matching placebo tiw with steroid tapering. The primary endpoint was the proportion of patients relapse-free at Week 26. Safety was also assessed. Results This study was terminated early following a planned interim analysis at 26 weeks. Of the planned 192 patients, 67 were randomized to treatment: placebo (n = 16), or IFN beta-1a 44 mcg biw (n = 17), 44 mcg tiw (n = 16) or 66 mcg tiw (n = 18). In total, 20/67 patients (29.9%) completed 26 weeks and 7 patients (10.4%) completed 52 weeks. The proportion of patients who remained relapse-free at Week 26 did not differ significantly between the placebo group (5/16, 31%) and the IFN beta-1a 44 mcg biw (6/17, 35%; p = 0.497), 44 mcg tiw (7/16, 44%; p = 0.280) or 66 mcg tiw (2/18, 11%; p = 0.333) groups. There was little difference between treatment groups in secondary efficacy endpoints. IFN beta-1a was generally well tolerated at all doses. Adverse events (AEs) were generally mild or moderate in IFN beta-1a-treated patients, with the most common AEs (influenza-like symptoms, headache, injection-site reactions) being similar to those reported with IFN beta-1a in MS. Conclusion There was no difference in efficacy between patients with CD receiving IFN beta-1a or placebo. However, these results should be considered in the context of the low patient numbers and high dropout rate. Overall, IFN beta-1a was generally well tolerated, with a safety profile that was consistent with previous experience in MS. Trial registration ClinicalTrials.gov NCT00304252

Why be put off by jealous colleagues who make school-boy jokes about bums and bottoms? True, detailed enquiries into bowel habits are necessary for the resolution of many patients' complaints, but actual faeces play a small part in the life of the well-organized gastroenterologist. Discussions of bowel habit should be as detached and cerebral as su-doku, and modern bowel preparations leave the colon as clear as crystal.

Introduction : Exclusion and low-fibre diets relieve symptoms in many cases of irritable bowel syndrome (IRS), but their mechanism of action is poorly understood. IRS often develops after the use of antibiotics or gastroenteritis, factors which may affect the colonic flora. Chemotaxonomy allows the assessment of anaerobic bacterial flora without the need for culture, by measuring bacterial cell wall fatty acids which are specific for differing species. Methods: 18 patients fulfilling the Rome criteria for IRS were divided into groups of 6 and randomised to receive either an exclusion diet, or a fibre-free diet (Fortisip, Cow & Gate, Nutricia Ltd) for two weeks, or a normal diet and one week on metronidazole 400mgs t.d.s. Symptoms were assessed by a validated symptom score and fecal specimens collected both before treatment, and on the final day of the study. 109 fecal slurries were made and filtered before extraction of bacterial fatty acids by saponification, methylation, extraction and a base wash followed by gas liquid chromatography (Hewlett Packard, USA). Results: The table shows the median values for the four most frequent fatty acids expressed as a percentage of the value on the normal diet. (FAME=fatty acid methyl ester, significance tested by Wilcoxon signed rank). Symptoms improved on both exclusion and fibre-free diet and in these groups significant alterations were found in the fatty acid composition of fecal bacteria. Metronidazole by contrast produced only temporary symptomatic improvement and did not affect significantly the bacterial fatty acids. Conclusion: The benefits of exclusion diet and fibre-free diets in IBS may be linked to their effects on the colonic flora. 4960