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Biomedical subjects

E Carty

Publications and source records attributed to E Carty.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of new therapies for inflammatory bowel disease.

The pathophysiology of inflammatory bowel disease (IBD) is gradually being unravelled and new therapies are being developed to target the disturbed biological processes. This article outlines the clinical features of IBD, its current therapy and pathogenesis. The difficulties for clinical pharmacologists and gastroenterologists associated with designing, executing and interpreting clinical trials in IBD are then discussed. The final section reviews methods that can used to demonstrate the pharmacological actions of new treatments in patients with IBD. It is emphasized that proof of the therapeutic efficacy of a novel agent with a specific mechanism of action yields not only clinical benefit to patients with IBD, but also indicates the importance of the targeted biochemical pathway in the pathogenesis of the disease.

Biopsy↗
PubMed2002

Thromboxane synthase immunohistochemistry in inflammatory bowel disease.

BACKGROUND: Thromboxanes are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthase inhibitor, is anti-inflammatory and may have therapeutic benefits in patients with ulcerative colitis. AIMS: To investigate the immunohistochemical expression of thromboxane synthase in the colorectal mucosa of patients with inflammatory bowel disease. METHODS: Immunostaining of colonic biopsies from patients with inflammatory bowel disease (n = 13) and controls (n = 5) was performed using a monoclonal antibody to human thromboxane synthase. The extent of staining in cells of the lamina propria was compared in patient and control groups, and was assessed in relation to disease activity scored macroscopically and histologically. RESULTS: The percentage of cells in the lamina propria staining for thromboxane synthase was higher in patients with active inflammatory bowel disease than in those with inactive disease or in controls (p = 0.02 and p = 0.002, respectively). There was a direct correlation between disease activity, measured endoscopically and histologically, and the percentage of lamina propria cells staining for thromboxane synthase (R = 0.71, p = 0.001 and R = 0.72, p = 0.001, respectively). CONCLUSIONS: Increased thromboxane synthase expression in lamina propria cells occurs in active inflammatory bowel disease. It is possible that this results in increased thromboxane synthesis, which may in turn contribute to mucosal inflammation and intramucosal thrombogenesis.

Adult↗
PubMed2001

Lack of efficacy of ridogrel, a thromboxane synthase inhibitor, in a placebo-controlled, double-blind, multi-centre clinical trial in active Crohn's disease.

BACKGROUND: Thromboxanes are produced in excess and platelets are activated in active Crohn's disease. Preliminary reports have suggested that ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist, may have therapeutic benefit in patients with inflammatory bowel disease. AIMS: To investigate the efficacy of ridogrel in patients with active Crohn's disease. PATIENTS AND METHODS: This was an international, multicentre, randomized, double-blind, placebo-controlled trial of 5 mg/day oral ridogrel for 12 weeks in 85 patients with moderately active Crohn's disease. Sixty patients were randomized to receive ridogrel, and 25 to placebo. The Crohn's disease activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey-Bradshaw index, global evaluation by the investigator and the patient, and blood measures of inflammation, were used as secondary outcomes. RESULTS: The patients' mean (s.d.) CDAI at recruitment was 277 (68) in the ridogrel treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) patients who had been given ridogrel in an intention-to-treat analysis and seven out of 25 (28%) patients given placebo were in remission (no significant difference). No significant differences in Harvey- Bradshaw index or global evaluation were noted between patients given ridogrel and those given placebo. Adverse events were similar in both groups. CONCLUSION: A 5-mg dose of oral ridogrel was not more effective than placebo in inducing remission in patients with moderately active Crohn's disease. If thromboxane synthesis and platelet function are to be targeted for the treatment of Crohn's disease, more potent agents require development and assessment.

Adult↗
PubMed2000

Ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist: anti-inflammatory profile in inflammatory bowel disease.

BACKGROUND: Thromboxanes, prostaglandins, reactive oxygen metabolites and pro-inflammatory cytokines are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthesis inhibitor and receptor blocker, may have therapeutic benefits in ulcerative colitis. AIMS: To investigate the anti-inflammatory profile of ridogrel. METHODS: The effects of ridogrel on the production of eicosanoids, reactive oxygen metabolites and cytokines by cultured inflamed colorectal mucosal biopsies were made using ELISA and chemiluminescence, reactive oxygen metabolite generation in a cell-free system, and platelet activation using flow cytometry. The effects of oral ridogrel on mucosal release of eicosanoids in two patients with active ulcerative colitis were assessed using rectal dialysis. RESULTS: Ridogrel significantly reduced the release of thromboxane B2, but not prostaglandin E2 or tumour necrosis factor-alpha, from biopsies (P < 0.01 for 10 microM ridogrel). Ridogrel showed no direct antioxidant activity but significantly reduced reactive oxygen metabolite production from cultured biopsies (P < 0.01 for 10 microM ridogrel). Platelet activation in vitro was inhibited by ridogrel (P </= 0.05 for >/= 10 microM ridogrel). Mean rectal mucosal thromboxane B2 release was reduced to 86% of pre-treatment levels in two patients treated with oral ridogrel. CONCLUSIONS: Its inhibition of mucosal production of thromboxane B2, reactive oxygen metabolites, and of platelet activation, suggests that ridogrel could have a therapeutic role in inflammatory bowel disease.

Adult↗
PubMed2000

Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel disease.

BACKGROUND: Platelets play an important role in inflammation and are activated in inflammatory bowel disease. Micro-vascular thrombosis in the gut wall leading to intestinal micro-infarction may be a pathogenic feature of Crohn's disease. 5-Aminosalicylic acid is an effective treatment for patients with inflammatory bowel disease. AIMS: To assess the effects of 5-aminosalicylic acid on platelet activation, when taken orally and in vitro by patients with inflammatory bowel disease. METHODS: Spontaneous and thrombin-induced platelet activation were studied using fluorescent antibodies to the activated platelet surface glycoprotein P-selectin and flow cytometry. RESULTS: Baseline platelet activation in inflammatory bowel disease was significantly greater than that in controls (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex-vivo platelet activation was 50% lower in patients with inflammatory bowel disease taking 5-aminosalicylic acid orally than in those not on such treatment (P < 0.05). In vitro, 5-aminosalicylic acid significantly reduced both spontaneous (P < 0. 03 for >/=1 microM 5-aminosalicylic acid) and thrombin-induced platelet activation (P < 0.02 for >/= 1 microM 5-aminosalicylic acid). CONCLUSIONS: 5-Aminosalicylic acid given either orally or in vitro inhibits platelet activation. If this effect reflects an in vivo action in the gut, it could contribute to the beneficial actions of 5-aminosalicylic acid in inflammatory bowel disease.

Adult↗
PubMed2000

Measurement of in vivo rectal mucosal cytokine and eicosanoid production in ulcerative colitis using filter paper.

BACKGROUND: Excessive mucosal generation of cytokines and eicosanoids has been reported in vitro in ulcerative colitis (UC) using traumatising biopsy techniques, and in vivo using time consuming rectal dialysis. AIMS: To validate a simple filter paper technique to profile rectal mucosal production of cytokines and eicosanoids in vivo in patients with UC compared with controls. PATIENTS: Forty one patients with UC (21 with active disease) and 16 controls were studied. METHODS: In vitro, recovery of known concentrations of cytokine or mediator applied to filter papers was measured by ELISA following incubation in buffer. In vivo, patients and controls had filter papers apposed to the rectal mucosa briefly through a rigid sigmoidoscope. Filter papers were then incubated prior to assay by ELISA. RESULTS: In vitro validation studies showed that the filter paper technique could be used to measure mucosal release of interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), thromboxane B(2) (TXB(2)), and prostaglandin E(2) (PGE(2)), but not interferon gamma (IFN-gamma). Mucosal release of IL-1beta, TNF-alpha, TXB(2) and PGE(2) were significantly increased in active UC (p=0.001) and correlated directly with disease activity (p=0.02). CONCLUSIONS: The filter paper technique confirmed increased rectal mucosal release of cytokines and eicosanoids in UC, in proportion to disease activity. The simplicity, safety and speed of the technique make it a practicable option for use in the outpatient clinic to study the pathogenesis of inflammatory bowel disease, and potentially its response to treatment.

Adult↗
PubMed1999

Use of mean platelet component to measure platelet activation on the ADVIA 120 haematology system.

Platelet activation results in changes in a number of cell surface molecules including an increase in P-Selectin (CD62P) that may be rapidly and conveniently measured by immunofluorescent flow cytometry. The ADVIA 120 (Bayer) is a new system that facilitates more accurate measurement of platelet volume and in addition provides an approximate measure of the mean refractive index (RI) of the platelets reported as mean platelet component (MPC) concentration. We were interested to determine whether changes in MPC might reflect changes in platelet activation status. To investigate this, the platelet CD62P expression, determined by flow cytometry, and change in MPC, measured on the ADVIA 120 system, was first examined in vitro after stimulation of EDTA anticoagulated whole blood with submaximal concentrations of bovine thrombin in the presence or absence of the thromboxane synthase inhibitor, Ridogrel. Thrombin produced a dose-dependent increase in platelet CD62P expression and a decrease in MPC that could be inhibited by Ridogrel at physiological concentrations. In the second set of experiments, blood from 20 normal controls was collected into both EDTA and sodium citrate (SC) anticoagulants. Within 30 min of venesection and again at 3 h post-venesection after storage at room temperature, the platelet MPC and CD62P expression were determined. Platelets in all samples with both anticoagulants showed very low levels of CD62P expression when first analysed. At 3 h there was a small increase in CD62P expression on platelets in whole blood anticoagulated with SC, but a significant (P < 0.001) increase was observed on platelets anti-coagulated with EDTA. A negative correlation was found between the change in MPC of the platelets and the increase in the mean fluorescence intensity (MFI) (r = -0.69, P < 0.001, n = 20) and the percentage (r = -0.72, P < 0.001, n = 20) of CD62P positive platelets at 3 h in blood anticoagulated with EDTA. We conclude that a reduction in MPC as measured by the ADVIA 120 may be used to detect anticoagulant induced, as well as thrombin stimulated, in vitro platelet activation in blood anticoagulated with EDTA. Further, we conclude that platelet activation is negligible for up to 3 h in sodium citrate anticoagulated whole blood.

Adult↗
PubMed1997

Community resources for frail older patients.

The goal of community-based services for frail older patients is to help them achieve the greatest degree of functional ability and independence. The services available include case management, geriatric assessment, adult day health care, home health services, and the Program for All-inclusive Care for the Elderly (PACE). Definitive criteria for referral have not been established, but without some targeting, the efficacy of these services remains uncertain. Targeting criteria identified include dependency in 2 or more activities of daily living, no family support, dementia, many long-term illnesses, and many hospital stays. Although efficacy and cost-effectiveness remain uncertain, patients, families, and physicians generally report these services to be helpful.

Aged↗
PubMed1983

Skeletons in the closet: exploring personal family background as a prerequisite for family nursing.

A nurse's family background, values and experiences will either positively or negatively affect the kind of care he or she gives. This depends on whether the nurse either has explored his/her background and uses it as a valuable resource or fails to see that it may affect care or even be a restriction to quality care. An individual can take specific steps to use family background as a potent and valuable resource. This paper describes a collection of self-directed and group exercises developed at the University of British Columbia School of Nursing that can be used to explore family background and hence use it more positively.

Adult↗
PubMedDate not supplied

Deconstructing the gender neutrality of chronic illness and disability.

Although a great deal has been written in the fields of women's health and disability/chronic illness, there is surprisingly little cross-fertilization. The dominant narrative within society orients us toward a view of chronic illness and disability that is gender neutral and devoid of social context. Examination of the ways in which chronic illness and disability are differently experienced by men and women creates a foundation upon which the implications of the dominant narrative can be explored. In this analysis, the authors find clinical, sociopolitical, and theoretical implications that derive from the traditional reluctance to consider the intersection of these fields of study. They conclude with recommendations for broadening our vision, correcting the omissions within our knowledge, and rethinking our part in contributing to inequities within society.

Attitude to Health↗
PubMedDate not supplied

A curriculum for SHO training--what is it and why has it changed?

The Royal Colleges of Physicians have revised the core curriculum for SHOs in medicine and the medical specialties to make it objective based. The objectives, knowledge, skills and attitudes for 'core skills' use ward based and outpatient clinical scenarios in specialty areas. There are also important sections on 'generic skills' including communication skills, team-working skills etc., cross-specialty areas, training in practical procedures and selection of investigations. Only in up to 41% of posts do SHOs in medicine get regular appraisal. A new appraisal replacing the personal training record has been designed to help SHOs reflect on their experience and identify gaps in their training using the revised curriculum. The new edition of the core curriculum should also allow the RCPs to set standards on the assessment of competence of SHOs to inform the postgraduate deans' SHO RITA process.

Clinical Competence↗