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C D Holdsworth

Publications and source records attributed to C D Holdsworth.

At least 19 recordsLinked to original sources
PubMed2002

A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis.

BACKGROUND: Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule. AIM: To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis. METHODS: A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology. RESULTS: Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission. CONCLUSIONS: Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.

Administration, Oral↗
PubMed2001

Does adjuvant nutritional support diminish steroid dependency in Crohn disease?

BACKGROUND: Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored. METHODS: Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy. RESULTS: The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement. CONCLUSION: Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease.

Adult↗
PubMed1998

Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group.

BACKGROUND & AIMS: Aminosalicylates are widely used in the treatment of ulcerative colitis (UC). Balsalazide is a novel mesalamine prodrug, activated by colonic bacteria. The aim of this study was to compare the efficacy and safety of balsalazide with that of a pH-dependent formulation of mesalamine in active UC. METHODS: A randomized, double-blind study was performed comparing balasalazide, 6.75 g daily, with mesalamine, 2.4 g daily, administered for 4, 8, or 12 weeks to 101 (99 evaluable) patients with symptomatic, sigmoidoscopically verified UC. RESULTS: More patients treated with balsalazide achieved symptomatic remission after 2 (64% [balsalazide] vs. 43% [mesalamine]), 4 (70% vs. 51%), 8 (78% vs. 45%), and 12 weeks (88% vs. 57%) and complete remission (none/mild symptoms, sigmoidoscopy grade 0/1, no rectal steroid use within 4 days) after 4 (38% vs. 12%), 8 (54% vs. 22%), and 12 weeks (62% vs. 37%). Patients taking balsalazide experienced more asymptomatic days (4 weeks, 24% vs. 14%) and achieved the first asymptomatic day more rapidly (median, 10 vs. 25 days). Fewer patients in the balsalazide group reported adverse events (48% vs. 71%); four serious adverse events occurred in the mesalamine group. CONCLUSIONS: Balsalazide is more effective and better tolerated than mesalamine as treatment for acute UC.

Adult↗
PubMed1998

Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group.

BACKGROUND: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. AIM: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. METHODS: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. RESULTS: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. CONCLUSIONS: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.

Adolescent↗
PubMed1995

Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease.

Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation.

Amino Acids↗
PubMed1995

Quantitative assessment of overall inflammatory bowel disease activity using labelled leucocytes: a direct comparison between indium-111 and technetium-99m HMPAO methods.

The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method.

Adolescent↗
PubMed1994

Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist.

BACKGROUND/AIMS: Ulcerative colitis and Crohn's disease have well-recognized familial tendencies, but the genetic basis of this clinical observation remains unknown. The cytokine interleukin-1 receptor antagonist is a potent anti-inflammatory protein that can prevent immune-mediated bowel inflammation in animals. We have previously characterized a polymorphism within the gene for this cytokine and others in the genes for the proinflammatory cytokines interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor alpha. The aim of this study was to determine whether inflammatory bowel disease was associated with particular alleles of these polymorphic cytokine genes. METHODS: The allelic frequencies of these polymorphic cytokine genes were determined in patients with ulcerative colitis (n = 113), Crohn's disease (n = 78), and healthy controls (n = 261). RESULTS: Allele 2 of interleukin-1 receptor antagonist was significantly over-represented in the ulcerative colitis patients: 35% versus 24% in controls (P = 0.007). Carriage of at least one copy of this allele gave an odds ratio of 2.0 for ulcerative colitis compared with controls. This association with allele 2 of interleukin 1 receptor antagonist was greatest in patients with total colitis and was not seen in Crohn's disease. There were no associations between UC and any of the other cytokine genes examined. CONCLUSIONS: This observation provides evidence that interleukin-1 receptor antagonist may have a role in determining the genetic susceptibility to and pathogenesis of ulcerative colitis.

Adult↗
PubMed1994

Background subtraction: a new approach to the assessment of disease activity in Crohn's disease using 99mTc-HMPAO-labelled leucocytes.

A computer-based technique for the quantification of abnormal bowel uptake in Crohn's disease has been developed and compared with pre-existing clinical, laboratory and scintigraphic methods of assessment. The standard technique for labelling leucocytes with 99mTc-HMPAO is applied. Images were obtained at 40, 120 and 240 min after the injection of radiolabelled leucocytes. The count in the bowel area after subtracting background activity corrected to the injected dose and image acquisition times is the 'scan score', an objective measure of disease activity. The scan score is significantly higher in patients with clinically active disease (mean 82.1 +/- SEM 13.6) than in those with quiescent disease (24.7 +/- 7.0) (p < or = 0.005). Optimum separation between active and quiescent disease is achieved with a threshold scan score of 20. The scan score was comparable in small bowel disease (73.3 +/- 16.2), large bowel (94.4 +/- 33) and disease at both locations (94.1 +/- 19.2). The scan score correlated favourably with Crohn's Disease Activity Index (rs = 52, p < or = 0.0001), Harvey & Bradshow Simple Index (rs = 0.4, p < or = 0.001), serum C-reactive protein (rs = 0.72, p < or = 0.001), serum alpha acid glycoprotein (rs 0.67, p < or = 0.001), haemoglobin (rs = 0.66, p < or = 0.001), platelet count (rs = 0.47, p < or = 0.006), albumin (rs = 0.61, p < or = 0.0001) and faecal 111Indium excretion (rs = 0.78, p < or = 0.001), but not with the ESR (rs = 0.22, p < or = 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Crohn Disease↗
PubMed1993

Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis.

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.

Adolescent↗
PubMed1993

Quantification of disease activity in Crohn's disease by computer analysis of Tc-99m hexamethyl propylene amine oxime (HMPAO) labelled leucocyte images.

The reliability and clinical applications of computerised image analysis measurement of bowel uptake of Tc-99m HMPAO labelled leucocytes has been examined as a measure of disease activity in Crohn's disease. In 54 studies carried out on 33 patients with established Crohn's disease, the mean 'scan score', a quantitative assessment of image intensity, was 82.1 SEM (13.6), in patients with clinically active disease compared to 24.7 (7.0) in those with quiescent disease, p < or = 0.0005. A significant correlation was found between the scan score and Crohn's Disease Activity Index (rs = 0.52, p < 0.0001), and Harvey and Bradshaw Simple Index (rs = 0.4, p < 0.004). A low scan score correctly identified seven patients whose raised Crohn's Disease Activity Index incorrectly indicated active disease because symptoms used in calculation of the index were not caused by active inflammation. Of the laboratory measurements, the scan score correlated with the haemoglobin (rs = 0.66, p < 0.0001), albumin level (rs = -0.6, p < 0.0001), C-reactive protein (rs = 0.7, p < 0.0001), alpha-acid glycoprotein (rs = 0.57, p < 0.001), and platelet count (rs = 0.47, p < or = 0.006), but not with the erythrocyte sedimentation rate (rs = 0.2, p < or = 0.25). The scan score was raised in all patients who had clinically active disease but normal laboratory tests. The results of this study indicate that the scan score provides an objective indicator of disease activity in Crohn's disease which may be superior to clinical indices, and also to laboratory tests which although objective are often normal in the presence of active disease.

Acute Disease↗
PubMed1992

99Tcm HMPAO-labelled leucocyte imaging in Crohn's disease: a subtraction technique for the quantification of disease activity.

A new technique for the quantitative analysis of labelled leucocyte images from patients with inflammatory bowel disease is described. The method involves the computer generation of a 'background' image which, after appropriate registration, is subtracted from the patient's image to leave a residue which represents abnormal uptake in the bowel. Quantification of the residual activity yields a scan score which can be related to the level of disease activity in patients with Crohn's disease. In 54 investigations on 33 patients the scan scores correctly agreed with a clinical assessment of disease activity in 16 of 20 cases with inactive disease and 32 out of 34 cases with active disease. Most of the discrepancies reflected inaccuracies in the clinical assessment of activity rather than shortcomings of the imaging technique.

Crohn Disease↗
PubMed1992

Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine.

The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side-effects of sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also assessed in these patients. Thirty-nine (91%) patients were able to tolerate at least one of the three 5-ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5-ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5-ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5-ASA containing preparations and that the side-effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5-ASA and sulphapyridine.

Aminosalicylic Acids↗
PubMed1992

Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day.

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.

Adult↗
PubMed1992

Virulence properties of Escherichia coli strains isolated from patients with inflammatory bowel disease.

Escherichia coli strains cultured from 74 patients with inflammatory bowel disease at different stages of disease activity (Crohn's disease (40), ulcerative colitis (34)) and 18 healthy controls were studied in relation to haemolysin and verotoxin production and enteroadherence. Disease activity was assessed by standard clinical and laboratory tests. Haemolytic E coli were isolated from 18% of patients with Crohn's disease, 24% with ulcerative colitis, and 11% of healthy controls. None of these differences was significant. No verotoxin producing strains were detected among the 216 E coli isolates examined but the extract from five strains (Crohn's (4), ulcerative colitis (1) produced a distinctive cytopathic effort on Vero cell monolayers which was later shown not to be due to verotoxin. The adhesion indices of E coli isolates cultured were: mean (SEM) 42.2 (6.4) for Crohn's disease, 43.3 (6.2) for ulcerative colitis, and 11.3 (2.0) for normal controls (p less than or equal to 0.0001). Adhesive E coli were isolated from 62% of patients with Crohn's disease and 68% with ulcerative colitis but from only 6% of normal controls (p less than or equal to 0.0002). Neither haemolysin production nor enteroadherence was dependent upon disease activity, disease location, sulphasalazine treatment, or previous intestinal resection. These results indicate that only enteroadherent E coli were frequently associated with inflammatory bowel disease; their relation to the pathogenesis of these conditions, however, remains uncertain.

Adult↗
PubMed1992

Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance.

Saccharomyces cerevisiae (baker's yeast) may play an important part in the pathogenesis of Crohn's disease. Because of this the levels of IgG and IgA antibodies against three S cerevisiae strains (NCYC 77, NCYC 79, and NCYC 1108) were assayed in 49 patients with Crohn's disease, 43 with ulcerative colitis, 14 with coeliac disease, and 21 healthy controls. Coded serum samples were tested by ELISA. Similar antibody patterns to all three strains were found. IgG and IgA antibody levels were significantly raised in patients with Crohn's disease compared with healthy controls (p < 0.001 and p < 0.0001 respectively) and with ulcerative colitis patients (p < 0.0001 and p < 0.0006 respectively). Raised IgA, but not IgG, yeast antibody levels were found in two patients with Crohn's disease who were intolerant to yeast, but these values were similar to those in other patients without yeast intolerance. In ulcerative colitis, both IgG and IgA levels were similar to normal controls. Patients with small bowel Crohn's disease had significantly higher IgG antibody levels than those with colonic disease (p < 0.01). High levels of IgG, but not IgA, antibody were present in patients with coeliac disease, the antibody responses being indistinguishable from those found in Crohn's disease. It is concluded that the presence of IgG antibody to S cerevisiae is characteristic but not specific to Crohn's disease. Although raised IgA antibody levels are more frequently found in Crohn's disease, their pathogenic importance remains to be established.

Adult↗
PubMed1991

The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique.

A semi-quantitative bacteriological method was used to study faecal flora in 42 patients with Crohn's disease, 37 with ulcerative colitis and 21 healthy controls. Faecal homogenates were plated on primary isolation plates by a technique that allowed the growth of various microbial isolates to be assessed on a visual 1(+)-5+ score. This method was first calibrated against a standard quantitative bacteriological technique, which confirmed the reliability and reproducibility of the results obtained by the simpler method. Patients with clinically active Crohn's disease (22) had significantly higher total aerobe scores than patients with quiescent disease (20) (p less than or equal to 0.006) or ulcerative colitis (p less than or equal to 0.04) or normal controls (p less than or equal to 0.02). The scores of Escherichia coli were parallel to those of total aerobes. Lactobacillus and bifidobacteria scores were significantly reduced in patients with Crohn's disease compared to those with ulcerative colitis and controls. The anaerobic flora in both Crohn's disease and ulcerative colitis was indistinguishable from that of controls. Bacteroides vulgatus and B. fragilis were the predominant bacteroides in all groups. Patients with ulcerative colitis, regardless of disease activity, harboured faecal flora that did not differ from that of normal controls. The abnormal faecal flora in Crohn's disease did not correlate with established clinical and laboratory indicators of disease activity.

Adult↗