bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chemoprevention of colorectal carcinoma
Authors: Gasche C. 
Published: December 2004

SummaryThis review aims to provide an insight into some of the common pathways involved in the development of colorectal cancer — so‐called chromosomal instability and microsatellite instability. There is both clinical and molecular evidence to show that colorectal cancer development occurs over an extended period of time. Together with a knowledge of the molecular pathogenesis of colorectal cancer, this time window allows physicians to counteract cancer development, a strategy known as chemoprevention. In familial and sporadic colorectal cancer, aspirin, other nonsteroidal anti‐inflammatory drugs and cyclo‐oxygenase‐2 inhibitors have been tested for their ability to reduce polyp and cancer development in clinical studies. In inflammatory bowel disease‐related colorectal cancer, evidence from retrospective case–control studies shows that mesalazine (mesalamine) can reduce the development of dysplastic lesions or cancer. Although the mechanisms behind this are incompletely understood, general anti‐inflammatory, oxygen scavenger and some pro‐apoptotic and cyclo‐oxygenase inhibitory activities of mesalazine are thought to be involved. New molecular evidence points to a direct DNA stabilizing effect of mesalazine, resulting in a significant reduction of spontaneous microsatellite mutations.
The role of nutrition in the treatment of inflammatory bowel disease
Authors: Gassull M. A. 
Published: December 2004

SummaryNutrients may be involved in the modulation of the immune response through at least three different mechanisms. First, the intestinal ecosystem plays a pivotal role in the pathogenesis of inflammatory bowel disease, triggering the uncontrolled inflammatory response in genetically predisposed individuals. Nutrients, together with bacteria, are major components of, and can therefore influence, the intestinal environment. Second, as components of cell membranes, nutrients can mediate the expression of proteins involved in the immune response, such as cytokines, adhesion molecules and nitric oxide synthase. The composition of lipids in the cell membrane is modified by dietary changes and can influence cellular responses. Indeed, various epidemiological, experimental and clinical data suggest that the immune response may be sensitive to changes in dietary composition. Finally, suboptimal levels of micronutrients are often found in both children and adults with inflammatory bowel disease, although, with the exception of iron and folate, it is unusual to discover symptoms attributable to these deficits. However, subclinical deficits may have a pathophysiological significance, as they may favour the self‐perpetuation of the disease (due to defects in the mechanisms of tissue repair), cause defective defence against damage produced by oxygen free radicals and facilitate lipid peroxidation. These events can occur even in clinically inactive or mildly active disease, as well as in the development of dysplasia in the intestinal mucosa. Some dietary manipulations have been attempted as primary treatment for rheumatoid arthritis, and specially formulated diets for enteral nutrition have proved to be an effective treatment for Crohn's disease. Most trials, although lacking sufficient patient numbers, have demonstrated a role for dietary manipulation as primary therapy for inflammatory disease. Dietary lipids are one of the most active nutritional substrates modulating the immune response. Recently, it has been demonstrated that lipids may be a key factor explaining the therapeutic effect of clinical nutrition in Crohn's disease.
Chronic active disease and maintaining remission in Crohn's disease
Authors: Kamm M. A. 
Published: December 2004

SummaryThe clinical management of Crohn's disease can be considered in relation to the treatment of acute disease and the maintenance of remission. The medication used to achieve these two goals may or may not be the same. Some patients with mildly active disease may respond to high‐dose (4 g/day) mesalazine (mesalamine), and 5‐aminosalicylic acid may also be helpful in weaning a patient off steroids after treatment for a flare‐up. However, the value of 5‐aminosalicylic acid in maintaining remission in Crohn's disease remains controversial. Subgroups of patients may be helped: for example, patients with Crohn's disease who have experienced a relapse within the last 2 years may benefit. Steroids form the first‐line therapy for acute episodes of inflammation but do not maintain remission. Azathioprine and mercaptopurine are the first‐line drugs for the maintenance of remission in moderate to severe Crohn's disease, and by titrating the dose up from 2 mg/kg daily, some previously resistant patients will be brought into remission. One‐half of patients who do not tolerate azathioprine will tolerate mercaptopurine. Methotrexate is effective in inducing and maintaining remission, and is useful for patients who fail azathioprine treatment. Thalidomide is not proven in controlled studies, but two open studies have demonstrated its efficacy. The optimal dose, however, remains to be defined. Purified liquid diets with food exclusion can induce remission in patients with active disease, but food exclusion is difficult to maintain long term. Infliximab can induce and maintain remission in patients resistant to other therapies, with two‐thirds of patients initially responding to treatment. One‐third go into remission and, of those who respond to a single treatment, approximately one‐half maintain remission when treated regularly for a year. Infliximab is, however, associated with an increased risk of infection, and its effect on cancer incidence is uncertain. The development of antibodies against the drug is associated with a loss of effect and allergic infusion reactions. In summary, simple proven therapies should be used first, because of their safety and benefit in some patients. However, aggressive therapy should be used when needed.
Patients' fears and unmet needs in inflammatory bowel disease
Authors: Irvine E. J. 
Published: December 2004

SummaryThe management of chronic illness is becoming increasingly patient‐centred. Although patients with inflammatory bowel disease have a normal life expectancy, most individuals experience an impact of inflammatory bowel disease on their daily lives as well as on their attitudes, fears and beliefs. Although currently available therapies for ulcerative colitis and Crohn's disease are becoming increasingly effective, there are still many unmet needs to address in this patient population. Physicians and patients' spouses or significant others underestimate the type and severity of problems reported by inflammatory bowel disease patients. Physical problems are frequently measured using disease activity indices. Emotional and social problems are reported using quality of life questionnaires and other specific measurement tools pertinent to the question of interest. Studies have indicated a poorer physical and emotional function in inflammatory bowel disease patients than in the general population. Effective therapies, both medical and surgical, produce significant improvements in the general and disease‐specific quality of life. The quality of life is worse when the disease is more severe. Concomitant anxiety or depression appears to impair the quality of life even further. Common fears include the possibility of unanticipated flares, the need for surgery, poor energy levels and the side‐effects of medication. Recent studies have suggested that more prominent patient participation in management has the potential for greater patient satisfaction, better outcomes and more efficient health resource utilization. Thus, future studies should focus not only on ensuring the wider availability of effective therapies, but on increasing access to health care that is tailored to individuals — more structure for some and more independence and self‐management for others, with health provider supervision.
The long‐term management of ulcerative colitis
Authors: Hanauer S. B. 
Published: December 2004

SummaryAfter the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The ‘optimal’ maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate‐induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long‐term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long‐term goals of maintenance therapy (e.g. prevention of relapse, reduction of long‐term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti‐inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.
Skin complications associated with inflammatory bowel disease
Authors: Tavarela Veloso F. 
Published: December 2004

SummaryCutaneous manifestations are well‐recognized complications of Crohn's disease and ulcerative colitis. The incidence of these manifestations varies widely but, at the time of diagnosis, the mean incidence is around 10%. During the course of the disease, a great variety of skin lesions may develop, many of which are secondary to granulomatous cutaneous disease, reactive skin eruptions, nutritional deficiency and other associated conditions. The disorders that are directly related to the inflammatory process of Crohn's disease include perianal and peristomal ulcers and fistulae, metastatic Crohn's disease and oral granulomatous lesions. Histologically, the features are similar to those found in the inflamed bowel. These lesions usually respond to treatment of the underlying intestinal disease. The most common forms of reactive skin eruption are erythema nodosum and pyoderma gangrenosum. Certain subsets of patients are more susceptible to the development of erythema nodosum; in a previous report from our group, erythema nodosum was seen mainly in females, and in patients with colonic involvement and/or arthritis. This manifestation tends to occur during the first 2 years of the clinical course of the disease and may recur in approximately one‐half of cases. Infliximab is highly effective in healing refractory lesions of erythema nodosum and pyoderma gangrenosum. Manifestations that are secondary to nutritional deficiency or associated conditions include acrodermatitis enteropathica, psoriasis and autoimmune disorders. For most of the cutaneous manifestations, the primary therapeutic target remains the bowel. Early aggressive therapy can minimize severe complications and maintenance treatment may prevent some devastating consequences.
The management of mild to severe acute ulcerative colitis
Authors: Travis S. P. L. 
Published: December 2004

SummaryThe goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high‐dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 °C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first‐line therapy, although the choice of 5‐aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.
Treatment of perianal fistulizing Crohn's disease
Authors: Rutgeerts P. 
Published: December 2004

SummaryFistulizing Crohn's disease can involve the bowel, but is more commonly seen in the perianal region. In acute perianal Crohn's disease, perianal lesions are manifestations of disease activity and are frequently treated concomitantly with bowel lesions. Spontaneous resolution occurs in up to 50% of patients. Fistulae are secondary lesions that may progress to destruction of the sphincter apparatus necessitating proctectomy after years of suffering. The control of sepsis is the first objective. The drainage of abscesses and the placement of setons are essential steps in treatment. Disease severity can be readily assessed by examination under anaesthesia and by magnetic resonance imaging. Endoscopic ultrasonography is sensitive, but is hampered by the necessary introduction of a large instrument into an often narrowed anorectum. Antibiotics, especially metronidazole and ciprofloxacin, are useful short‐term therapies to decrease or stop drainage, but relapse is immediate on discontinuation. Immunosuppression with azathioprine (2.5 mg/kg per day) or mercaptopurine (1.5 mg/kg per day) is effective, but slow and often incomplete. The management of perianal fistulizing disease resistant to standard treatment has greatly improved with the introduction of the anti‐tumour necrosis factor‐α antibody, infliximab. The complete arrest of the drainage of fistulae is obtained in 46% of patients 10 weeks after the administration of 5–10 mg/kg of infliximab at weeks 0, 2 and 6 and, on average, lasts for 12 weeks. A treatment algorithm for fistulizing Crohn's disease must therefore involve the early and optimal use of immunosuppression and of infliximab. Medical and surgical co‐operation is also critical to achieve the best possible outcome.
Inflammatory bowel disease — empowering the patient and improving outcome
Authors: Robinson A. 
Published: December 2004

SummaryInflammatory bowel disease, in common with most chronic diseases, is managed by specialist clinicians during regular clinic follow‐up visits. Patients spend approximately 1 h per year with clinicians, with few provisions made for patient participation in their own management for the remainder of the year, resulting in dependence and disempowerment. The provision of regular, fixed clinic appointments for diseases that follow an unpredictable relapsing/remitting pattern results in inefficiencies for health services and inconvenience for patients, as well as high rates of noncompliance. Self‐care is a normal human function and accounts for the management of three‐quarters of all episodes of ill health. More formalized applications include patients and doctors working collaboratively to develop a set of guidelines which patients use to manage their chronic disease themselves. Recent studies have shown that, in patients with stable ulcerative colitis, self‐management results in reduced health service utilization, speedier access to treatment and high levels of patient acceptability, without compromising health outcomes. There are a number of barriers to the effective implementation of guided self‐management at many levels. Clinicians may be reluctant to pass control of treatment changes to patients, particularly the use of steroids. Access to clinics at short notice may be difficult and some patients themselves prefer a system in which all decisions are made by doctors. Research into guided self‐management is ongoing as the long‐term outcomes are uncertain. However, there are indications that passing ‘ownership of management’ back to patients may improve compliance as patients realize their own responsibilities for remaining well.
Combination therapy for the treatment of hepatitis C in the veteran population: higher than expected rates of therapy discontinuation
Authors: Getachew Y. , Browning J. D. , Prebis M. , Rogers T. , Brown G. R. 
Published: December 2004

SummaryAim : To compare the efficacy of high‐dose induction with standard dose interferon therapy for the treatment of chronic hepatitis C virus at the Dallas Veterans Affairs Medical Center.Methods : Patients were randomized to receive 5 million units daily interferon‐α2b for 4‐weeks followed by 44‐weeks for genotype 1 or 20 weeks for non‐genotype 1 of standard dose therapy (3 million units three times a week) or standard dose therapy for total treatment duration. Daily weight‐based ribavirin was used for entire therapy interval.Results : Forty‐five patients were enrolled in the trial with genotype 1 comprising 75.6% of the sample. Cirrhosis or bridging‐fibrosis was present in 69% of the patients. Of the 29 liver biopsies available for Knodell scoring, 41% and 51% had scores of 6–10 and 11–15, respectively. Rates of sustained virological response did not differ significantly between the two treatment groups. Therapy type and/or early intervention for depression did not affect the rate of therapy discontinuation, which was 26.6%.Conclusion : The rate of sustained virological response was similar between the two treatment groups and higher than anticipated among patients with cirrhosis or bridging‐fibrosis. The rate of therapy discontinuation was also higher than anticipated but was not attributable to therapy type or untreated depression.
Cost‐effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease
Authors: Winter J. , Walker A. , Shapiro D. , Gaffney D. , Spooner R. J. , Mills P. R. 
Published: December 2004

SummaryBackground : Azathioprine is a useful agent in the management of inflammatory bowel disease. Its use is limited by its side‐effect profile. Marrow toxicity occurs in approximately 3.2% of patients and is known to be associated with diminished thiopurine methyltransferase enzyme activity resulting from genetic polymorphisms.Aim : To evaluate the cost‐effectiveness of screening for thiopurine methyltransferase gene polymorphisms prior to initiation of azathioprine therapy.Methods : Analysis of the literature was undertaken to calculate the expected frequency of leucopenia and its relationship with thiopurine methyltransferase polymorphisms in a model of theoretical inflammatory bowel disease patients. Decision analysis was then applied to assess the cost of a pre‐treatment genotyping strategy, taking account of direct costs and cost per life‐year saved.Results : In 1000 inflammatory bowel disease patients treated with azathioprine, 32 will develop myelosuppression and one will die because of this. Of those who develop myelosuppression during azathioprine therapy, 32% are attributable to lower thiopurine methyltransferase activity. Pre‐treatment genotyping costs £347 per life‐year saved for a 30 year old and £817 per life‐year saved for a 60 year old. This compares favourably with other health care technologies.Conclusion : The use of pre‐treatment screening for thiopurine methyltransferase polymorphisms in inflammatory bowel disease patients commencing azathioprine therapy represents good value for money.
Long‐term outcome and objective changes of anorectal function after biofeedback therapy for faecal incontinence
Authors: Ozturk R. , Niazi S. , Stessman M. , Rao S. S. C. 
Published: December 2004

SummaryBackground : In the short‐term, biofeedback therapy improves symptoms and anorectal function in patients with faecal incontinence but whether there is long‐term improvement is incompletely understood.Aim : To prospectively evaluate bowel symptoms and anorectal function, both immediately and 12 months after biofeedback therapy.Methods : A total of 105 consecutive patients (male/female = 12/93) with faecal incontinence, unresponsive to supervised medical treatment were enrolled in biofeedback training consisting of biweekly pelvic muscle strengthening exercises, anal squeeze and sensory‐motor coordination training, and reinforcement sessions at 3, 6 and 12 months. Anorectal manometry, saline continence test, stool diaries and bowel satisfaction scores were used to assess improvement.Results : 94/105 (male/female = 10/84) completed training and 11 dropped out. Sixty completed 1‐year assessment. At 1‐year, 63% reported no episodes of incontinence. Biofeedback decreased (P < 0.001) stool frequency and number of incontinence episodes and increased (P < 0.001) bowel satisfaction score, anal resting and squeeze pressures, squeeze duration and ability to retain saline infusion increased (P < 0.001), both immediately and at 1 year. Sensory thresholds decreased (P < 0.001).Conclusions : Biofeedback therapy produced sustained improvement in bowel symptoms and anorectal function. Because it is safe, inexpensive compared with other surgical interventions, and effective, biofeedback should be offered to incontinent patients unresponsive to medical therapy.