The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat

Background:

Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results.

Aim:

To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol.

Methods:

Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4.

Results:

TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance.

Conclusions:

Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

     

Gastrointestinal pH profiles in patients with inflammatory bowel disease

Background:

5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.

Aim:

To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen.

Methods:

Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn’s disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease).

Results:

The median gastric pH values in the patient groups (Crohn’s disease 2.4, range 1.5–4.1; ulcerative colitis 1.95, range 1.55–4.4) were significantly higher than those observed in the controls (1.55, range 0.95–2.6). In the small bowel and colonic segments, all the pH values of Crohn’s disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission.

Conclusions:

The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.

     

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders

Aim:

To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea.

Source:

Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these.

Results:

In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT₃ antagonists.

Conclusion:

Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

     

Anti-diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro

Background:

Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti-diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown.

Aim:

To examine the effect of seirogan on electrogenic ion transport in vitro.

Methods:

Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh).

Results:

Serosal or mucosal application of seirogan (0.1–100 μg/mL) decreased basal jejunal transmural PD. Pre-treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan-induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh-induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD.

Conclusion:

The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh-induced electrical responses, may contribute to its anti-diarrhoeal action.

     

Heparin and low-molecular-weight heparin (enoxaparin) significantly ameliorate experimental colitis in rats

Background and aims:

The anticoagulants, unfractionated heparin and low‐molecular‐weight heparin, demonstrated anti‐inflammatory effects in animal models and in humans. Because of its dual effects, high‐dose heparin was proposed as a therapeutic modality for ulcerative colitis. We investigated whether a low dose of low‐molecular‐weight heparin—enoxaparin (Clexane, Rhône‐Poulenc Rorer, France)—ameliorates the inflammatory response in two models of experimental colitis.

Methods:

Colitis was induced in rats by intrarectal administration of dinitrobenzene sulphonic acid. Enoxaparin (40, 80 and 200 μg/kg) or unfractionated heparin (100, 200 and 400 U/kg) were administered subcutaneously immediately after the induction of damage. Enoxaparin, 80 μg/kg, was also administered after induction of colitis by intrarectal administration of iodoacetamide. Rats were sacrificed 1, 3 or 7 days after induction of injury. Colonic damage was assessed macroscopically and histologically. Mucosal prostaglandin E₂ generation, myeloperoxidase and nitric oxide synthase activities and tumour necrosis factor‐α levels in blood were determined.

Results:

Enoxaparin and heparin significantly ameliorated the severity of dinitrobenzene sulphonic acid‐ and iodoacetamide‐induced colitis as demonstrated by a decrease in mucosal lesion area, colonic weight and mucosal myeloperoxidase and nitric oxide synthase activities. The dose–response curve had a bell‐shaped configuration: enoxaparin, 80 μg/kg, and unfractionated heparin, 200 U/kg, were the optimal doses.

Conclusions:

Low‐dose enoxaparin and unfractionated heparin ameliorate the severity of experimental colitis. This effect is related to their anti‐inflammatory rather than anticoagulant properties.

     

Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study

Background

Germinated barley foodstuff (GBF) has been shown to attenuate intestinal injury in animal models, largely by increasing luminal short-chain fatty acid production.

Aim

To investigate the safety and efficacy of GBF in the treatment of ulcerative colitis (UC).

Methods

Ten patients with active UC received 30 g of GBF daily for 4 weeks in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Pre- and post-treatment stool concentrations of short-chain fatty acids were measured by gas-liquid chromatography.

Results

Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 6.9 ± 1.4 to 2.8 ± 1.5 (mean ± S.E.M., P < 0.05). The endoscopic index score fell from 6.1 ± 2.3 to 3.8 ± 2.3 (P < 0.0001). Patients showed an increase in stool butyrate concentrations after GBF treatment (P < 0.05). No side-effects were observed.

Conclusions

Oral GBF therapy may have a place in management of ulcerative colitis, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

     

Effect of pepper and bismuth subsalicylate on gastric pain and surface hydrophobicity in the rat

Background

The mechanism by which dietary pepper causes dyspepsia and epigastric pain is poorly understood, as is the ability of bismuth subsalicylate (BSS) to relieve these symptoms.

Aim

To investigate the ability of black pepper, red pepper and BSS to affect gastric surface hydrophobicity and induce/relieve visceral pain in rat model systems.

Methods

Fasted rats were administered intragastrically Vivonex containing varying concentrations of either black or red pepper (0–200 mg/mL) and gastric contact angles were read after 1–24 h. Some rats were post-treated with BSS (2.0–17.5 mg/mL) and contact angles were read after 2–18 h. To study pain sensitivity in rats treated with pepper/BSS, we compared tail-flick latencies after the application of radiant heat.

Results

Both black and red pepper rapidly (< 1 h) induced a decrease in gastric surface hydrophobicity in a dose-dependent fashion. This spice-induced increase in surface wettability was long-lasting, could be enhanced in the presence of ethanol and reversed by post-treating the rats with BSS. Both black and red pepper induced an increase in pain sensitivity, consistent with the presence of gastric pain, which could also be reversed by post-treating the rats with BSS.

Conclusion

Both black and red pepper may induce epigastric pain by removing the stomach’s hydrophobic lining and activating intramucosal pain receptors. BSS may provide relief from postprandial dyspepsia by restoring the stomach’s non-wettable properties.

     

Dialysis of the rectum for sampling drug concentrations in the luminal extracellular fluid of the gut: technique and precision

Background:

It is useful to measure the luminal concentration of drugs which act in the gut. Dialysis of the rectum has not previously been used or validated for this purpose.

Aim:

To determine the precision of rectal dialysis for measuring rectal drug concentrations.

Methods:

To establish the duration of dialysis required to approach equilibrium, the rate of methotrexate diffusion into dialysis bags was first determined in vitro. The precision of rectal dialysis for sampling the methotrexate concentration of colonic lumen extracellular fluid was determined in seven subjects who underwent two consecutive dialysis procedures. Subjects treated with subcutaneous methotrexate for refractory inflammatory bowel disease were studied.

Results:

Methotrexate crossed the dialysis membrane by a first-order process, and after a 2 h in vitro dialysis, equilibration was 74 ± 2% (mean ± s.d.) complete. Rectal dialysis was well tolerated by all subjects. The mean ± s.e. methotrexate concentration of 3.6 ± 1.1 nmol/L in the first dialysate was not significantly different from 3.6 ± 0.9 nmol/L in the second dialysate, P = 0.99 (paired two-tailed t-test). Similar precision was obtained for an endogenous molecule, potassium, secreted by the rectal mucosa.

Conclusions:

Dialysis of the rectum is a well tolerated and precise technique for sampling the colonic lumen extracellular fluid for quantitative analyses of exogenous and endogenous substances.

     

Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome

Background:

Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome.

Aim:

To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to distension with a barostat.

Methods:

Twenty-five irritable bowel syndrome patients were included in a randomized double-blind parallel group trial; data were available for 22 (Rome criteria; 48 ± 11 years; 13 men and nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain.

Results:

Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d.

Conclusion:

Alosetron increases the compliance of the colon to distension, and could thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.

     

Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy

Background:

Although the role of gastric digestion (by acid-dependent pepsins) in overall protein assimilation has never thoroughly been studied, it is generally considered to be limited. Protein that escapes assimilation in the small intestine is intensely fermented by the colonic flora. Phenol and p-cresol are specific bacterial metabolites of tyrosine.

Aim:

To elucidate the role of gastric digestion of protein by evaluating the influence of acid suppression therapy on overall protein assimilation and fermentation.

Methods:

Protein assimilation was studied in 16 healthy subjects under basal conditions and after omeprazole treatment using the combined ¹⁴C-octanoic acid/¹³C-egg white breath test. The degree of protein fermentation was estimated by measuring the urinary output of phenol and p-cresol in 41 healthy volunteers and in 17 patients treated for more than 1 month with omeprazole because of peptic disease.

Results:

Protein assimilation was significantly impaired after omeprazole treatment. Gastric emptying, conversely, was not affected. The urinary output of phenol and p-cresol was increased in patients treated with omeprazole as compared to untreated controls.

Conclusion:

Gastric acid suppression therapy hampers protein assimilation and may promote protein malabsorption. Gastric digestion is likely to play a substantial role in overall protein assimilation.

     

Conditional loss of TGF-beta signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice

Background:

Downregulation of TGF‐β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF‐β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis.

Methods:

We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF‐β type II receptor was expressed under the control of tissue‐specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA⁺ and VacA⁺) or administered with azoxymethane to determine the significance of loss of TGF‐β signalling in gastrointestinal carcinogenesis.

Results:

Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild‐type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF‐β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen‐labelling index when infected with H.pylori than wild‐type littermates (P < 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild‐type littermates.

Conclusions:

Maintaining normal TGF‐β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.

     

Beclomethasone dipropionate enemas versus prednisolone sodium phosphate enemas in the treatment of distal ulcerative colitis

Aim:

To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60mL enema (PP) once daily in patients with active distal ulcerative colitis.

Methods:

One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks.

Results:

Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic–pituitary–adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups.

Conclusions:

It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

     

Short- and long-term outcome of patients treated with cyclosporin for severe acute ulcerative colitis

Background:

Recent evidence suggests that the immunosuppressive drug cyclosporin may be of benefit in treating patients with severe colitis who are steroid resistant. Although cyclosporin appears to be effective in reducing colectomy rates in the short term, few data are available on the long-term follow-up of such patients.

Aim:

To investigate the short- and long-term outcome of patients with severe steroid-resistant ulcerative colitis treated with cyclosporin who were otherwise being considered for colectomy.

Methods:

Twenty-two patients with severe steroid-resistant exacerbations of ulcerative colitis who were being considered for colectomy were treated with cyclosporin (4 mg/kg i.v.) daily for 7 days followed by oral treatment (6 mg/kg/day) if colectomy was avoided.

Results:

Twenty of 22 patients (91%) avoided colectomy during their initial hospital admission. With a mean follow-up period of 39 months (range 31–59), eight of these patients have subsequently relapsed and required colectomy and 12 patients have avoided colectomy (53%). Of the 12 patients avoiding colectomy, seven have successfully been weaned on to azathioprine while five are maintained on an aminosalicylate alone. None of these long-term responders require maintenance corticosteroids. The main side-effects during treatment with cyclosporin were headaches (six patients, 27%), paraesthesia and tremors (four patients, 18%) and hypertension (four patients, 18%). Two patients developed renal impairment on cyclosporin which resolved on lowering the dose. In no case was cyclosporin discontinued because of an adverse reaction. No clinical or laboratory features could be identified that predicted which patients treated with cyclosporin would later require colectomy.

Conclusion:

This study shows that cyclosporin is a viable alternative to emergency colectomy in severe ulcerative colitis in the short term. Although these benefits are not maintained in all patients, more than half were found to avoid colectomy in the longer term.

     

Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis

Background:

To investigate the value of combined treatment with allopurinol and 5‐aminosalicylic (5‐ASA) based drugs as maintenance treatment for ulcerative colitis (UC).

Methods:

199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5‐ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months.

Results:

Intention‐to‐treat analysis after 6 and 12 months showed similar results in both groups. A log‐rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar.

Conclusions:

It appears possible that allopurinol in combination with 5‐ASA is better than 5‐ASA alone for a 6‐month, but not a 12‐month period. This has to be verified in further dose‐ranging studies.

     

Experimental colitis induced by dextran sulphate sodium in mice: beneficial effects of sulphasalazine and olsalazine

Background:

Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextran sulphate sodium (DSS) induced intestinal inflammation model has recently been shown to fulfil some pathological criteria for an adequate experimental model.

Aim:

To determine whether this form of experimental intestinal inflammation responds to established therapy used for human inflammatory bowel disease.

Methods:

DSS was used to induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD-1(BR) mice, and the well-documented 5-aminosalicylic acid (5-ASA) based anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study therapeutic effects. Parameters which have been shown to reflect DSS-induced intestinal inflammation (body weight, colon length, spleen weight, diarrhoea, and rectal bleeding) were measured in the Balb/c mice.

Results:

Significant amelioration was seen on these parameters after different treatment protocols. Survival in nu/nu CD-1 mice was studied, and after 16 days a death rate of 50% was noted in the DSS group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolonged the survival to 29 and 38 days, respectively. SASP and OLZ showed a dose-dependent effect in the range between 10 and 100 mg/kg/day, doses closely corresponding to those used in humans.

Conclusions:

SASP and OLZ are able to ameliorate the DSS-induced intestinal inflammation. The dose-response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5-ASA molecule.

     

Duplex-Doppler evaluation of the effects of propranolol and isosorbide-5-mononitrate on portal flow and splanchnic arterial circulation in cirrhosis

Background:

A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding.

Aim:

To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide-5-mononitrate, on splanchnic circulation.

Methods:

Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide-5-mononitrate.

Results:

The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide-5-mononitrate (≥ 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide-5-mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney.

Conclusions:

Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of ≥ 20% after the acute addition of isosorbide-5-mononitrate to chronic propranolol treatment.

     

Review article: the management of achalasia - a comparison of different treatment modalities

Summary

Background

Achalasia is an uncommon primary oesophageal motor disorder with an unknown aetiology. Therapeutic options for achalasia are aimed at decreasing the lower oesophageal sphincter pressure, improving the oesophageal empting, and most importantly, relieving the symptoms of achalasia. Modalities for treatment include pharmacologic, endoscopic, pneumatic dilatation and surgical. The decision of which modality to use involves the consideration of multiple clinical and economic factors.

Aim

To review the management strategies currently available for achalasia.

Methods

A Medline search identified the original articles and reviews the published in the English language literature between 1966 and 2006.

Results

The results reveal that pharmacotherapy, injection of botulinum toxin, pneumatic dilatation and minimally invasive surgical oesophagomyotomy are variably effective at controlling the symptoms of achalasia but that each modality has specific strengths and weaknesses which make them each suitable in certain populations. Overall, pharmacologic therapy results in the shortest lived, least durable response followed by botulinum toxin injection, pneumatic dilatation and surgery, respectively.

Conclusion

The optimal treatment for achalasia remains an area of controversy given our lack of complete understanding about the pathophysiology of the disease as well as the high numbers of clinical relapse after treatment. Further research focusing on optimal dosing of botulinum toxin injection and optimal timing of repeated graduated pneumatic dilatations could add to our knowledge regarding long‐term therapy.

     

Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis

Aim:

To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis.

Patients and methods:

Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks.

Results:

Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a non-significant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator’s global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine.

Conclusion:

Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.

     

Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin–tazobactam

Background

Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk.

Aim

To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin–tazobactam (PT).

Methods

A prospective, ward-based, crossover study was carried out on two well-matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad-spectrum antibiotic treatment.

Results

There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P = 0.001) and diarrhoea (18/34 vs. 1/14, P = 0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment.

Conclusions

Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.

     

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

Summary

Background

The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC).

Aim

To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC.

Methods

Ninety‐eight consecutive treatment‐naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM‐IV, at baseline and both during and after treatment.

Results

Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti‐viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one).

Conclusion

Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.