bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic active disease and maintaining remission in Crohn's disease
Authors: Kamm M. A.
Published: December 2004

The 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

The 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

After 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

Cutaneous 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

The 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

Fistulizing 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

Inflammatory 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

Aim : 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

Background : 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

Background : 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.
Oesophageal and gastric pH profiles in patients with gastro‐oesophageal reflux disease and Barrett's oesophagus treated with proton pump inhibitors
Authors: Gerson L. B. , Boparai V. , Ullah N. , Triadafilopoulos G.
Published: December 2004

Background : Acid plays a significant role in the development of gastro‐oesophageal reflux symptoms and tissue damage. It is generally assumed that acid suppressive therapy with proton pump inhibitors improves or eliminates symptoms of gastro‐oesophageal reflux disease by normalizing intra‐oesophageal pH. However, the degree of acid suppression induced by proton pump inhibitor therapy in patients with gastro‐oesophageal reflux disease and/or Barrett's oesophagus has not been adequately studied.

Aim : To assess the efficacy of proton pump inhibitors in normalizing intra‐oesophageal and intra‐gastric pH in patients with gastro‐oesophageal reflux disease with and without Barrett's oesophagus who have been rendered symptom‐free by acid‐suppressive therapy.

Methods : Patients with gastro‐oesophageal reflux disease and Barrett's oesophagus were prospectively evaluated by dual sensor 24‐h pH monitoring while receiving proton pump inhibitor therapy for complete control of gastro‐oesophageal reflux disease symptoms. Analyses and comparisons of intra‐oesophageal and intra‐gastric pH profiles on therapy were then made.

Results : One hundred and ten patients, 98 men and 12 women, with gastro‐oesophageal reflux disease (n = 62) and/or Barrett's oesophagus (n = 48), were studied. All tolerated proton pump inhibitors well and were asymptomatic at the time of the study. Thirty‐six (58%) patients with gastro‐oesophageal reflux disease and 24 (50%) patients with Barrett's oesophagus (P = 0.4) normalized their intra‐oesophageal pH profiles on proton pump inhibitors. Compared with patients with gastro‐oesophageal reflux disease, patients with Barrett's oesophagus were more likely to have higher degree of pathologic acid reflux despite proton pump inhibitor therapy (DeMeester score 50.5 ± 8.2 vs. 31.4 ± 4.6, P = 0.03) and exhibited less intra‐gastric acid suppression (% total pH<4.0: 53.9 ± 2.7 vs. 39.9 ± 2.6, P =0.0004), particularly supine (% pH<4.0: 62.1 ± 3.4 vs. 44.8 ± 3.4, P =0.0006).

Conclusions : Gastro‐oesophageal reflux disease patients with or without Barrett's oesophagus continue to exhibit pathologic gastro‐oesophageal reflux disease and low intra‐gastric pH despite proton pump inhibitor therapy that accomplishes complete reflux symptom control. Further, intra‐oesophageal and intra‐gastric pH control is significantly more difficult to achieve in patients with Barrett's oesophagus. These findings may have significant therapeutic implications.
Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology
Authors: Dolwani S. , Metzner M. , Wassell J. J. , Yong A. , Hawthorne A. B.
Published: December 2004

Backgound : Patients being investigated for symptoms of abdominal pain, diarrhoea and or weight loss often undergo small bowel radiology as part of their diagnostic workup mainly to exclude inflammatory bowel disease.

Aim : To assess and compare the utility of a single faecal calprotectin estimation to barium follow through as well as conventional inflammatory markers such as erythrocyte sedimentation rate and C‐reactive protein in exclusion of intestinal inflammation.

Methods : Seventy‐three consecutive cases undergoing barium follow through for investigation of symptoms of diarrhoea and or abdominal pain with or without weight loss were studied. The control group comprised 25 cases with known active Crohn's disease (positive controls), 26 normal healthy volunteers (negative controls) and 25 cases of irritable bowel syndrome diagnosed by Rome II criteria. Symptoms, erythrocyte sedimentation rate and C‐reactive protein were recorded at recruitment and a single stool sample assayed for calprotectin within 7 days prior to or after barium follow through.

Results : The median calprotectin value in the active Crohn's group, irritable bowel syndrome group and normal volunteers was 227 μg/g of stool, 19 and 10 μg/g respectively (P < 0.0001). A faecal calprotectin above a cut‐off value of 60 μg/g was able to predict all nine cases with an abnormal barium follow through as well as all six cases with a normal barium follow through but with organic intestinal disease. The negative predictive value of a single calprotectin result below 60 μg/g of stool was 100% compared with 91% each for erythrocyte sedimentation rate > 10 mm and C‐reactive protein > 6 mg/L and 84% for a combination of erythrocyte sedimentation rate and C‐reactive protein in predicting absence of organic intestinal disease.

Conclusion : A single stool calprotectin value < 60 μg/g of stool obviates the need for further barium radiology of the small bowel, is more accurate than measurement of erythrocyte sedimentation rate or C‐reactive protein and effectively excludes Crohn's disease or non‐functional gastrointestinal disease.
A pilot study of orlistat treatment in obese, non‐alcoholic steatohepatitis patients
Authors: Harrison S. A. , Fincke C. , Helinski D. , Torgerson S. , Hayashi P.
Published: December 2004

Background : Treatment options for non‐alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy.

Aim : To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH.

Methods : Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained.

Results : Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4–39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14–5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 –54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79–48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients.

Conclusions : Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost‐efficacy in comparison to diet and exercise alone.
Azathioprine formulation optimizes metabolite profile in inflammatory bowel disease
Authors: Stevens T. , Achkar J. P. , Easley K. , Brzezinski A. , Lashner B.
Published: December 2004

Background : Recent studies have suggested that mercaptopurine metabolism is influenced by drug formulation (mercaptopurine vs. azathioprine) and concomitant use of 5‐aminosalicylic acid medications.

Aim : To determine the influence of dose, formulation and 5‐aminosalicylic acid use on mercaptopurine metabolism.

Methods : Metabolites from 131 inflammatory bowel disease patients were analysed. Logistic regression was used to analyse correlations between dose and metabolite levels. Multivariate analysis was used to determine the effects of drug formulation and 5‐aminosalicylic acid use.

Results : A positive correlation was detected between dose and 6‐tioguanine nucleotides levels for azathioprine/Imuran formulation (P = 0.005) but not for mercaptopurine formulation. Adjusted mean 6‐tioguanine nucleotides levels were similar for both formulations. Adjusted mean 6‐methylmercaptopurine levels were higher for mercaptopurine formulation than for azathioprine formulation (1950 vs. 1056, P = 0.04). 5‐aminosalicylic acid use: 6‐tioguanine nucleotides levels did not differ based on concomitant 5‐aminosalicylic acid use. However, 5‐aminosalicylic acid use did result in higher adjusted mean 6‐methylmercaptopurine levels: 2078 on 5‐aminosalicylic acid vs. 991 off 5‐aminosalicylic acid (P = 0.004).

Conclusions : (i) Azathioprine may have metabolic benefits by achieving a correlation of dose with 6‐tioguanine nucleotides levels and by leading to lower mean 6‐methylmercaptopurine levels. (ii) 5‐aminosalicylic acid use does not significantly impact 6‐tioguanine levels and may lead to higher 6‐methylmercaptopurine levels.
Review article: the safety profile of tegaserod
Authors: Schoenfeld P.
Published: December 2004

Gastrointestinal symptoms are the most common side‐effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post‐US marketing randomized controlled trials. In most patients, tegaserod‐induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod‐treated and placebo‐treated patients. Pooled analysis of Phase III and post‐US marketing randomized controlled trials did not demonstrate significant differences between tegaserod‐treated and placebo‐treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod‐using patients in any Phase III or post‐marketing randomized controlled trials, and post‐marketing surveillance indicated that the rate of ischaemic colitis in tegaserod‐using patients was lower than that in non‐tegaserod‐using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod‐treated (6 mg b.d.) vs. placebo‐treated patients (15% vs. 12.3%, respectively; P < 0.05), although post‐US marketing randomized controlled trials did not demonstrate this increase. Other extra‐gastrointestinal adverse events occurred with similar frequency in tegaserod‐treated and placebo‐treated patients. Tegaserod‐treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo‐treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.
Review article: epidemiology and quality of life in functional gastrointestinal disorders
Authors: Chang L.
Published: December 2004

The epidemiology and health‐related quality of life associated with functional gastrointestinal disorders are reviewed, with particular emphasis on irritable bowel syndrome and functional dyspepsia. The literature supports the significant world‐wide prevalence of functional gastrointestinal disorders, including irritable bowel syndrome (IBS), functional dyspepsia and chronic constipation. An increased female prevalence has been demonstrated in most studies in patients with IBS and chronic constipation, but not functional dyspepsia. The female to male ratio appears to be greater in the health care‐seeking population than in community populations. However, some differences in the reported general prevalence and gender‐related prevalence of functional gastrointestinal disorders may be due to cultural factors and study methodology. A significant health care burden is associated with IBS, with increased out‐patient services, abdominal and pelvic surgeries, and gastrointestinal‐ and non‐gastrointestinal‐related physician visits and health care costs. Health‐related quality of life is impacted significantly in patients with functional gastrointestinal disorders, such as functional dyspepsia and IBS, compared with the general healthy population, as well as patients with other chronic medical conditions, such as gastro‐oesophageal reflux disease and asthma. Impaired health‐related quality of life has been demonstrated, in particular, in patients with moderate to severe disease seen in referral settings. The health‐related quality of life appears to improve in treatment responders, or correlates with symptom improvement, with at least some treatment modalities studied in functional gastrointestinal disorders, but further studies are needed. Predictors of health‐related quality of life in patients with functional gastrointestinal disorders include psychosocial factors, such as early adverse life events, and symptoms related to visceral perception, e.g. pain and chronic stress. The presence of extra‐intestinal symptoms appears to have a major if not greater impact on health care visits, excess health care costs and health‐related quality of life in patients with functional gastrointestinal disorders.
Quality of life in patients with established inflammatory bowel disease: a UK general practice survey
Authors: Rubin G. P. , Hungin A. P. S. , Chinn D. J. , Dwarakanath D.
Published: December 2004

Background : The current understanding of quality of life impairment in inflammatory bowel disease has largely been derived from selected populations and may not reflect the experience of patients in the community, where fewer than half are likely to be under specialist care.

Aim : To describe the health‐related quality of life in a community‐based sample of patients with established inflammatory bowel disease and explore its association with the type and extent of disease, gender, age, material deprivation and other factors.

Methods : Adults with established inflammatory bowel disease were identified systematically from the records of 23 family practices in north‐east England. The health‐related quality of life was assessed by self‐completion of the UK Inflammatory Bowel Disease Questionnaire.

Results : Five hundred and fifty‐six patients were sent the questionnaire and 409 (74%) gave usable replies. Lower scores (worse quality of life) were significantly associated with female gender, Crohn's disease, more extensive disease (ulcerative colitis) and being under specialist care. The mean health‐related quality of life score was significantly lower in patients resident in more deprived districts, independent of the type and extent of disease.

Conclusions : Most patients with established inflammatory bowel disease showed only minor impairment of their health‐related quality of life. On average, women and those with Crohn's disease were relatively more affected. Clinicians responsible for the care of patients with inflammatory bowel disease should be aware of these more vulnerable groups.
The influence of ageing on the insulin signalling system in rat lacrimal and salivary glands
Authors: Rocha Eduardo M. , Carvalho Carla R. O. , Saad Mário J. A. , Velloso Lício A.
Published: December 2004

Purpose:  Ageing adversely affects the structure and function of lacrimal and salivary glands (LG and SG) and leads to marked insulin resistance that correlates with reduced insulin signal transduction. The aim of this study was to investigate whether ageing affects insulin signal transduction in LG and SG in vivo.

Methods:  Male Wistar rats aged 20 months and 2 months (control group) were compared (n = 8/group). Samples were removed under anaesthesia after i.v. injection of insulin, homogenized, immunoprecipitated with anti‐insulin receptor (IR), Shc and STAT‐1 antibodies and immunoblotted with antiphosphotyrosine antibody.

Results:  The 20‐month‐old rats were significantly hyperinsulinaemic and presented a reduced rate of blood glucose disappearance in response to insulin, compared to the 2‐month‐old rats. The level of phosphorylation determined by densitometry in the older group of rats showed that ageing significantly reduced insulin‐induced IR phosphorylation in LG and SG and STAT‐1 phosphorylation in SG, compared to in the control group, but did not alter Shc phosphorylation.

Conclusions:  Ageing influences insulin signal transduction in the LG and SG of rats. Considering the major anabolic actions of insulin, these observations may help to explain the mechanisms of LG and SG dysfunctions observed in ageing.
Topical versus peribulbar anaesthesia for cataract surgery
Authors: Sauder Gangolf , Jonas Jost B.
Published: December 2004

Background:  To assess and compare the efficacy and safety of topical versus peribulbar anaesthesia in patients undergoing routine cataract surgery.

Methods:  The unicentre, prospective, randomized, clinical interventional trial included 140 consecutive patients undergoing routine cataract surgery performed by one of two surgeons. The patients were randomly distributed to either peribulbar anaesthesia or topical anaesthesia. To assess intraoperative pain, each patient was asked immediately after surgery to quantitate his/her pain using a 10‐point pain rating scale.

Results:  The study groups did not differ significantly in pain score (p = 0.54), duration of surgery (p = 0.52), anaesthesia‐related intraoperative difficulties (p = 0.17), postoperative visual acuity (p = 0.94), overall intraoperative surgical complication rate, blood pressure rise (p = 0.16) or blood oxygen saturation (p = 0.74)

Conclusions:  Patient comfort and surgery‐related complications did not differ between topical anaesthesia and peribulbar anaesthesia. As there are no significant differences between the two techniques in terms of subjective pain experienced by patients, intraoperative complications and postoperative visual outcome, and in view of the minimally invasive character of topical anaesthesia compared to peribulbar anaesthesia, the present study suggests the use of topical anaesthesia for routine cataract surgery.
Melanoma‐associated spongiform scleropathy: biochemical changes and possible relation to tumour extension
Authors: Alyahya Ghassan Ayish , Ribel‐Madsen Søren M. , Heegaard Steffen , Prause Jan Ulrik , Trier Klaus
Published: December 2004

Purpose:  To investigate biochemical changes of the sclera in eyes with melanoma‐associated spongiform scleropathy (MASS), and to analyse possible relationships between these changes and tumour extension.

Methods:  Sections from 364 eyes, enucleated for choroidal and ciliary body melanoma, were examined for MASS and scleral tumour extension. Biochemical analysis was also performed on eight scleral specimens with MASS and eight specimens (controls) from morphologically normal sclera of the same eyes. The scleral thickness of each specimen was measured. Samples were delipidized, dried and weighed. The weight ratios of collagen‐related amino acids were calculated based on quantitation by liquid chromatography. Amounts of glycosaminoglycans (GAGs) were determined by electrophoresis.

Results:  Melanoma‐associated spongiform scleropathy was seen in 140 eyes (38.5%). Tumour scleral extension was observed in 82 eyes. Of these 82 eyes, 75 (91.5%) had MASS (p < 0.05). Biochemically, the majority of the main amino acids of the scleral collagen and total proteins were significantly lower in areas with MASS than in the control specimens. Specific GAGs and total GAGs were found in significantly higher concentrations in areas with MASS than in the control specimens. Scleral thickness was also significantly higher in areas with MASS than in the control specimens.

Conclusions:  The reduced content of collagen manifested by decreased amino acids and total proteins indicates collagen degradation in the vicinity of the tumour. The concomitant excessive deposition of GAGs accumulates water and may cause loosening of the already degraded collagen bundles, giving a histopathological picture of MASS. These changes could facilitate tumour cell migration and may explain the high incidence of MASS in eyes with scleral tumour extension.
Outcome of zone 1 retinopathy of prematurity
Authors: O'Keefe Michael , Lanigan Bernadette , Long Vernon W.
Published: December 2004

Purpose:  To describe the outcome in a series of patients with pre‐threshold and threshold zone 1 retinopathy of prematurity.

Methods:  We performed a retrospective analysis of 12 babies, 24 eyes, with zone 1 retinopathy of prematurity, treated between 1992 and 2002 with diode laser treatment.

Results:  Ten out of the 12 babies had an unfavourable outcome. The only patients with successful anatomical outcomes were those treated before threshold disease occurred. All babies had developmental delay or neurological disability.

Conclusion:  Zone 1 retinopathy of prematurity has a poor anatomical and visual prognosis and many of the babies in our study had developmental delay and neurological disability. Earlier treatment may improve the visual outcome.
Corneal penetration of levofloxacin into the human aqueous humour: a comparison with ciprofloxacin
Authors: Colin Joseph , Simonpoli Sylvie , Geldsetzer Klaus , Ropo Auli
Published: December 2004

Purpose:  To compare aqueous humour levels of levofloxacin and ciprofloxacin following topical application to patients scheduled for cataract surgery.

Methods:  A total of 59 patients undergoing cataract surgery were randomly assigned to topical treatment with either levofloxacin 0.5% or ciprofloxacin 0.3% eye drops, at one drop every 15 min for four doses immediately prior to surgery. Aqueous humour samples were collected by paracentesis and analysed for drug content.

Results:  The (geometric) mean aqueous humour concentration of levofloxacin was 0.728 µg/ml; that of ciprofloxacin was 0.080 µg/ml.

Conclusions:  Levofloxacin achieves 9.1 times the aqueous humour concentration of ciprofloxacin. It could be considered a better choice than ofloxacin or ciprofloxacin for topical ophthalmic use.
Nordic research in ophthalmology
Authors: Stefánsson Einar , Zetterström Charlotta , Ehlers Niels , Kiilgaard Jens F. , La Cour Morten , Sigurdsson Haraldur , Gudmundsdóttir Elínborg , Prause Jan Ulrik , Heijl Anders
Published: December 2004

Purpose: To provide an overview of some of the current activities in eye research in the Nordic countries.

Methods: The presentations at the biannual Nordic Congress of Ophthalmology, held in Tampere, Finland in 2002, were reviewed and the contributions found most noteworthy are included in this article along with a limited discussion of each research field. However, space requirements prevented the inclusion of many interesting scientific contributions.

Results: Important contributions in various subfields of eye research and ophthalmology are reviewed. These include cornea, cataract, paediatric ophthalmology, glaucoma, diabetic eye disease, age‐related macular degeneration, physiology and pharmacology and oncology.

Conclusions: Eye research is very active in the Nordic countries and significant contributions are being made to ophthalmology in several fields on a world scale. We hope to continue to review Nordic contributions to eye research after each Nordic Congress of Ophthalmology and plan to make the reviews more systematic and comprehensive in the future.
Deep sclerectomy in patients with capsular glaucoma
Authors: Drolsum Liv
Published: December 2004

Purpose:  To compare the results of deep sclerectomy in capsular glaucoma (CG) with those in primary open‐angle glaucoma (POAG).

Methods:  This consecutive, prospective study comprised 24 CG patients (28 eyes) and 25 POAG patients (29 eyes) who underwent deep sclerectomy. Two different implants were used: either an absorbable collagen implant (Aqua‐Flow®) or a non‐absorbable hydrophilic acrylic implant (T‐Flux®). The number of glaucoma medications, intraocular pressure (IOP) and complications were compared postoperatively. The definition of complete success was IOP below 19 mmHg without therapy.

Results:  After a mean follow‐up of 19.9 ± 10.9 months (range 6–36 months) in the CG group and 16.2 ± 10.0 months (range 6–36 months) in the POAG group, complete success was seen in 60.7% and in 37.9% of eyes, respectively (p = 0.085). After adjustments for disparities in baseline characteristics, survival analysis demonstrated that success rates were better over time in CG eyes than in POAG eyes (p = 0.038). At all time‐points, except at 24 months, the IOP was lower in the CG group than in the POAG group. This difference was statistically significant at 1 week (p = 0.050) and 3 months (p = 0.006). At 18 months, the mean decrease in number of medications was 77.3% in the CG group and 65.9% in the POAG group (not statistically significant). Levelled hyphema occurred more frequently in CG eyes (35.7%) than in POAG eyes (13.8%).

Conclusion:  Capsular glaucoma patients had significantly higher success rates over time than POAG patients following deep sclerectomy with implant.
Consideration of the posterior corneal curvature for assessment of corneal power after myopic LASIK
Authors: Langenbucher Achim , Torres Francia , Behrens Ashley , Suarez Enrique , Haigis Wolfgang , Seitz Berthold
Published: December 2004

Purpose:  To evaluate the effect of a separate measurement of the anterior and posterior corneal surface to calculate the total refractive power of the cornea after myopic laser in situ keratomileusis (LASIK).

Methods:  A total of 39 eyes of 21 patients (aged 33 ± 9 years) were included in this prospective, non‐randomized, comparative study. These involved 19 myopic corrections (− 3.5 ± 1.6 dioptres) and 23 refractive corrections of myopic astigmatism (sphere: − 3.7 ± 1.6 D, cylinder: − 1.2 ± 0.4 D). All procedures were accomplished with the Keratom II®. Coherent‐Schwind excimer laser and the Moria Model One® microkeratome (150 µm head) at the Medical Education Centre, La Trinidad, Caracas, Venezuela. Subjective refractometry, Bausch & Lomb® keratometry and Orbscan® slit‐scanning corneal topography analysis were performed before and 3 months after LASIK. Corneal power was assessed directly using keratometry (K1) and Orbscan videokeratography (T1). Corneal power was calculated using the preoperative keratometric (K2, ‘gold standard’, clinical history method) or topographic power (T2, clinical history method) and spherical equivalent change. A composite value was derived from the Orbscan anterior and posterior surface power and central pachymetry (T3).

Results:  Three months postoperatively, corneal power ranged in a descending order from T1 (42.33 ± 1.78 D), K1 (40.82 ± 2.20 D), K2 (40.42 ± 2.36 D), T2 (40.03 ± 2.51 D) to T3 (38.78 ± 2.23 D). On average, T1 exceeded the gold standard by 1.9 D and the gold standard exceeded T3 by 1.6 D. K2, T1, T2 and T3 correlated significantly with K1 (r = 0.975, p < 0.001; r = 0.909, p < 0.001; r = 0.963, p < 0.001; r = 0.853, p < 0.001, respectively). The differences T1−K2 (r = − 0.699, p < 0.001) and T3−K2 (r = − 0.499, p = 0.001) correlated highly inversely and K1−K2 correlated borderline inversely (r = − 0.325, p = 0.043) with the intended refractive correction.

Conclusion:  After myopic LASIK, refractive corneal power is overestimated by direct keratometric and especially videokeratoscopic measurements. The higher the intended refractive correction, the greater is this error. A separate measurement of both refractive surfaces of the cornea tends to underestimate but may enhance accuracy of the total refractive corneal power if the history of the patient is unknown.
Telangiectasis as a cause of intra‐schitic haemorrhage in optic disc pit maculopathy
Authors: Quinn Shauna M. , Charles Stephen J.
Published: December 2004

Purpose:  To present a patient with the novel finding of vascular telangiectasis as a cause of intra‐schitic haemorrhage, occurring in optic disc pit‐associated maculopathy.

Methods:  A clinical history was detailed. Clinical examination included visual acuity assessment and slit‐lamp microscopy. Fluorescein angiography was performed.

Results:  A temporal optic disc pit, macular retinoschisis and a circumscribed detachment of the outer retinal layer and inner leaf holes were noted. A retinal haemorrhage extending into the schitic cavity was present, along with an associated vitreous haemorrhage. Fluorescein angiography showed telangiectatic vessels in association with the haemorrhage.

Conclusion:  This is the first reported case of vascular telangiectasis as a cause of intra‐schitic haemorrhage occurring in optic disc pit‐associated maculopathy.