'Sticky' neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.

Dwarakanath, A D; Yu, L G; Brookes, C.L.; Pryce, D.W.; Rhodes, JM

doi:10.1136/gut.37.4.585

Cited by 67 publications

(28 citation statements)

References 29 publications

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“…Gaffney and colleagues reported 10 patients, nine of whom responded, 4 and a large controlled Russian study reported a reduction in colectomy rate for severe colitis from 19.4% (control) to 6.2% (heparinized). 3 Recently we reported a patient with ulcerative colitis complicated by pyoderma gangrenosum who had a dramatic response to heparin 7 and speculated that the heparin might be exerting its effect via inhibition of neutrophil recruitment. We now report our further experience with the use of intravenous heparin in hospitalized patients with corticosteroidresistant ulcerative colitis.…”

Section: Introductionmentioning

confidence: 99%

Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases

Evans

Wong

Morris

et al. 1997

Aliment Pharmacol Ther

135

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Background:Heparin, a group of sulphated glycosaminoglycans, in addition to its anticoagulant activity, has a wide range of potentially anti‐inflammatory effects. These include inhibition of neutrophil elastase and inactivation of chemokines. Previous reports of fortuitous improvement in ulcerative colitis patients treated with heparin for prophylaxis of venous thrombosis, prompted us to perform a pilot study in patients with corticosteroid‐resistant ulcerative colitis.Methods:Sixteen hospitalized patients in relapse from ulcerative colitis and unresponsive to high‐dose corticosteroid therapy were treated with intravenous standard heparin (subcutaneous in two patients), the dose was adjusted to provide standard anticoagulant activity. Five patients continued with subcutaneous injections on discharge, with a gradual reduction in the frequency of doses.Results:Within 1 week of starting heparin, 12/16 patients had shown a considerable reduction in stool frequency. After 2 weeks of heparin therapy median stool frequency had improved from 8.0/day (range 6.3–10.0) pre‐treatment to 3.5/day (2.5–5.25) (P=0.008), and by 4 weeks 12/16 achieved clinical remission. Four patients required elective colectomy. Three patients were treated with heparin on a second occasion during a relapse, two failed to respond and required subsequent colectomy. Nine remain well. No serious complications were seen due to the anticoagulant activity, apart from bruising at subcutaneous injection sites.Conclusion:The response to heparin in patients with ulcerative colitis resistant to standard therapy is encouraging and supports the previous uncontrolled evidence for a therapeutic effect. A controlled trial of heparin in ulcerative colitis is clearly indicated.

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Section: Introductionmentioning

confidence: 99%

Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases

Evans

Wong

Morris

et al. 1997

Aliment Pharmacol Ther

135

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“…2,3 Interestingly, unfractionated heparin (UFH) has been found to reduce symptoms and improve healing in patients with GCS-refractive ulcerative colitis, 4±7 and also to be bene®cial against extraintestinal manifestations in ulcerative colitis. 8,9 In an uncontrolled study, 90% of the patients achieved complete remission. 4 However, this positive effect appeared to be dependent on concomitant SASP treatment, although these patients had not previously responded to SASP per se.…”

Section: Introductionmentioning

confidence: 99%

Low molecular weight heparin as adjuvant therapy in active ulcerative colitis

Törkvist

Thorlacius

Sjöqvist

et al. 1999

Aliment Pharmacol Ther

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Background: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions.Aim: To assess the tolerability and safety of subcutaneous self‐administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect.Patients and Methods: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study.Results: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved.Conclusion: Self‐administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids‐refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.

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“…[123] Such effects were seen in patients with RA, [124] asthma [125] and ulcerative colitis. [126] A potential mechanism of action is inhibition of leukocyte extravasation through binding to the beta-2 integrin CD11b/CD18. [127;128] An intriguing possibility is the development of new agents that retain the antiinflammatory properties of heparin, but without the anticoagulant Kovesdy and Kalantar-Zadeh Page 10…”

Section: Sevelamer Hydrochloride-sevelamermentioning

confidence: 99%

Novel targets and new potential: developments in the treatment of inflammation in chronic kidney disease

Kövesdy

Kalantar-Zadeh

2008

Expert Opinion on Investigational Drugs

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Background-Patients with chronic kidney disease (CKD) of all stages experience extremely high mortality, with cardiovascular causes accounting for about half of all their deaths. Traditional risk factors such as hypertension, hypercholesterolemia and diabetes mellitus cannot explain the excessively high cardiovascular mortality in CKD. Chronic inflammation is one of the novel risk factors that appear to contribute to the increased mortality seen in patients with CKD. Therapeutic interventions targeting chronic inflammation in CKD may lead to improved outcomes.Objectives-To describe the role of inflammation in CKD and to review antiinflammatory pharmacologic therapies that could have a role in its therapy. Methods-Review of the literature and expert opinion.Results/Conclusion-Inflammation is a common and significant problem in CKD. There are currently no approved pharmacologic antiinflammatory therapies in CKD, but several agents are being studied in early clinical trials, while others could become viable alternatives in the future.

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'Sticky' neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.

Cited by 67 publications

References 29 publications

Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases

Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases

Low molecular weight heparin as adjuvant therapy in active ulcerative colitis

Novel targets and new potential: developments in the treatment of inflammation in chronic kidney disease

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