Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

Background—The relapse rate after steroid inducedremission in Crohn's disease is high.
Aims—To test whether oral pH modified releasebudesonide (3 × 1 mg/day) reduces the relapse rate and to identifypatient subgroups with an increased risk of relapse.
Methods—In a multicentre, randomised, doubleblind study, 179 patients with steroid induced remission of Crohn'sdisease received either 3 × 1 mg budesonide (n=84) or placebo (n=95)for one year. The primary study aim was the maintenance of remission ofCrohn's disease for one year.
Results—Patient characteristics at study entrywere similar for both groups. The relapse rate was 67% (56/84) in thebudesonide group and 65% (62/95) in the placebo group. The relapsecurves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. Noprognostic factors allowing prediction of an increased risk for relapseor definition of patient subgroups who derived benefit from low dosebudesonide were found. Drug related side effects were mild and nodifferent between the budesonide and the placebo group.
Conclusion—Oral pH modified release budesonide ata dose of 3 × 1 mg/day is not effective for maintaining steroidinduced remission in Crohn's disease.

Keywords:budesonide; Crohn's disease; maintenance ofremission

     

Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States

OBJECTIVES: Budesonide controlled ileal release (CIR) capsules deliver budesonide, a glucocorticosteroid with high topical and low systemic activity, to the distal ileum and the proximal colon. In four previous controlled trials in Crohn's disease, remission rates ranged from 51% to 69%. We sought to evaluate the efficacy and safety of this drug in a population of patients in the United States with Crohn's disease. METHODS: In this multicenter, double blind, randomized trial, 200 patients in the United States with mild to moderate Crohn's disease (Crohn's Disease Activity Index [CDAI] between 200 and 450) involving the distal ileum and/or ascending colon received 9 mg of budesonide CIR once daily, 4.5 mg b.i.d., or placebos for 8 wk. The primary outcome was remission defined by a CDAI of 150 or less. RESULTS: Remission was achieved in 48%, 53%, and 33% with 9 mg once daily, 4.5 mg b.i.d., and placebos, respectively, after 8 wk of treatment. Differences between the groups were not significant. The differences in mean change from baseline CDAI between the combined budesonide and placebo groups was significant (p < 0.05). There was no difference in observed adverse events between treatment groups, although a modest decrease in plasma cortisol levels was observed relative to the placebo (p < 0.01). CONCLUSIONS: Treatment of symptomatic Crohn's disease with budesonide CIR capsules (9 mg daily) was safe, and remission rates were similar to those achieved in previous trials. Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo.     

Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo

Aims—To investigate the efficacy of dailymaintenance treatment with omeprazole 10 mg in reducing the relapserate of healed erosive oesophagitis.
Methods—Three hundred patients with erosiveoesophagitis (grade 2 or greater) received omeprazole 20 mg daily for12 weeks, followed by 40 mg daily for a further 12 weeks if required.After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse thetreatment cycle was repeated.
Results—The cumulative healing rate at 12 weeksin the initial healing period was 95%, and 96% and 98% on rehealingcourses after relapse in the first and second maintenance periodsrespectively. After 12 weeks of treatment, 98% of patients were freefrom heartburn and 97% were free of all reflux related symptoms.Relapse in the subgroup of patients who relapsed in both maintenanceperiods was infrequent on omeprazole 20 mg daily: only 9% at twoyears. Gastrin concentrations rose above normal in one third ofpatients. One patient had linear hyperplasia of endocrine cells andanother had micronodular hyperplasia. There were no side effectsdefinitely attributable to omeprazole.
Conclusion—Maintenance treatment with omeprazole10 mg daily keeps about 60% of patients with erosive oesophagitis inprolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20mg daily.

Keywords:erosive oesophagitis; long term maintenancetreatment; omeprazole

     

Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients

OBJECTIVE—To determine the effect of adjunctive prednisolone on morbidity, pericardial fluid resolution, and mortality in HIV seropositive patients with effusive tuberculous pericarditis.
DESIGN—Double blind randomised placebo controlled trial.
SETTING—Two medical school affiliated referral hospitals in Harare, Zimbabwe.
PATIENTS—58 HIV seropositive patients aged 18-55 years with tuberculous pericarditis.
INTERVENTIONS—All patients received standard short course antituberculous chemotherapy and were randomly assigned to receive prednisolone or placebo for six weeks.
MAIN OUTCOME MEASURES—Clinical improvement, echocardiographic and radiologic pericardial fluid resolution, and death.
RESULTS—29 patients were assigned to prednisolone and 29 to placebo. After 18 months of follow up there were five deaths in the prednisolone treated group and 10 deaths in the placebo group. Mortality was significantly lower in the prednisolone group (log rank χ² = 8.19, df = 1, p = 0.004). Resolution of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and ascites (p = 0.015), and improvement in physical activity (p = 0.02), were significantly more rapid in the prednisolone treated patients. However, there was no difference in the rate of radiologic and echocardiographic resolution of pericardial effusion.
CONCLUSIONS—Adjunctive prednisolone for effusive tuberculous pericarditis produced a pronounced reduction in mortality. It is suggested prednisolone should be added to standard short course chemotherapy to treat HIV related effusive tuberculous pericarditis.


Keywords: tuberculous pericarditis; HIV infection; echocardiography; prednisolone     

Medium term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea

Background—Carcinoid diarrhoea is associated withrapid small bowel and proximal colonic transit. Intravenousadministration of a serotonin type 3 receptor (5HT₃)antagonist restores postprandial colonic tone towards normal incarcinoid patients.
Aims—To evaluate the medium term effects of anoral 5HT₃ antagonist, alosetron, on symptoms, stool fat,and transit in patients with carcinoid diarrhoea.
Methods—In 27 patients with carcinoid diarrhoea,symptoms were recorded daily and gastrointestinal transit was measuredby scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was givenduring the first week. Loperamide (2 mg capsules) was used as rescue medication.
Results—There were numerical improvements inmedian diarrhoea score, stool weight, loperamide use, and overallcolonic transit at four hours, but no overall significant drug effectwas shown. Alosetron reduced the proximal colon emptying rate (p<0.05in 20 evaluable comparisons), but did not significantly alter small bowel transit.
Conclusions—Alosetron retardation of proximalcolonic emptying in patients with carcinoid diarrhoea confirms thepotential role of a 5HT₃ mechanism in this disorder. Dosesof alosetron higher than 2.0 mg twice daily will be required forsymptomatic benefit in carcinoid diarrhoea.

Keywords:carcinoid diarrhoea; alosetron; serotoninergicagents; antagonist; colonic transit

     

One week triple therapy for Helicobacter pylori: a multicentre comparative study

Background—Eradication ofHelicobacter pylori cures and prevents the relapse ofduodenal ulceration and also results in histological resolution ofchronic active gastritis.
Aim—To compare four treatment regimenslasting seven days of a proton pump inhibitor and two antibiotics inthe eradication of H pylori.
Patients—Men or women with Hpylori positive duodenal ulceration or gastritis, or both.
Methods—A single blind, prospectively randomised,parallel group, comparative, multicentre study. After a positive CLOtest, patients underwent histology, H pylori culture, anda ¹³C urea breath test to confirm H pyloristatus. Treatment with one of four regimens: LAC, LAM, LCM, or OAM,where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillintwice daily, M is 400 mg of metronidazole twice daily, C is 250 mg ofclarithromycin twice daily, and O is 20 mg of omeprazole twice daily,was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.
Results—H pylori eradication(intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%)with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM.There was a significant difference (p < 0.001) in the proportion ofpatients in whom eradication was successful between LAC and LCM whencompared with LAM, but no significant difference (p = 0.15) between LAMand OAM. Metronidazole resistance before treatment was identified as asignificant prognostic factor with regard to eradication of Hpylori. The regimens which contained metronidazole weresignificantly less effective than those without metronidazole in thepresence of pretreatment resistant H pylori. There was nodifference among the treatment groups with regard to the incidence andseverity of adverse events reported.
Conclusions—All four treatment regimenswere safe and effective in eradicating H pylori in thepatient population studied. LAC was the most efficacious treatment inpatients with pretreatment metronidazole resistant Hpylori, and was significantly better than LAM and OAM in thisgroup of patients.

Keywords:eradication; Helicobacterpylori; lansoprazole; omeprazole; metronidazole resistance

     

The timing of glucocorticoid administration in rheumatoid arthritis

OBJECTIVE—To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process.
METHODS—26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group.
RESULTS—Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P << 0.001), joint pain (P < 0.001), Lansbury index (P << 0.001), Ritchie index (P << 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups.
CONCLUSIONS—Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

     

Antiplatelet treatment with cilostazol after stent implantation

Objectives—To evaluate the efficacy of cilostazol, a new synthetic inhibitor of phosphodiesterase, in preventing stent thrombosis after successful implantation.
Design—Preliminary prospective study.
Setting—A single coronary care unit in Japan.
Patients—Elective, bailout, or primary stents were implanted in 85 consecutive patients with 93 lesions. Primary stent implantation was performed in 18 patients with acute myocardial infarction. Patients received 200 mg cilostazol and 243 mg aspirin after stenting.
Main outcome measures—Stent thrombosis, major and minor complications, and side effects were assessed in the six months after stenting.
Results—Gianturco-Roubin stents were implanted in 37 lesions, Wiktor stents in 55, and Palmaz-Schatz stents in 27. Multiple stents were used in 26 lesions. There was no mortality, stent thrombosis related Q wave myocardial infarction, emergency bypass surgery, repeat intervention, or vascular complications in the six months of follow up. Acute or subacute closure did not occur after stenting. There were no serious side effects such as leucopenia and/or abnormal liver function for three months. Cilostazol was withdrawn in one patient because of skin rash. Patients who underwent primary stenting had no clinical events, such as acute or subacute thrombosis, or side effects.
Conclusions—Cilostazol is an effective antiplatelet agent with minimum side effects after elective, bailout, or primary stent implantation.

Keywords: antiplatelet treatment; stents; stent thrombosis; cilostazol     

Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus

Background—Both acid and duodenal contents arethought to be responsible for the mucosal damage in Barrett'soesophagus, a condition often treated medically. However, little isknown about the effect of omeprazole on duodenogastric reflux (DGR) andduodenogastro-oesophageal reflux (DGOR).
Aims—To study the effect of omeprazole 20 mgtwice daily on DGR and DGOR, using the technique of ambulatorybilirubin monitoring.
Methods—Twenty three patients with Barrett'soesophagus underwent manometry followed by 24 hour oesophageal andgastric pH monitoring. In conjunction with pH monitoring, 11 patients(group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before andduring treatment with omeprazole 20 mg twice daily.
Results—In both groups there was a significantreduction in oesophageal acid (pH<4) reflux (p<0.005) and asignificant increase in the time gastric pH was above 4 (p<0.005). Ingroup 1, median total oesophageal bilirubin exposure was significantlyreduced from 28.9% to 2.4% (p<0.005). In group 2, median totalgastric bilirubin exposure was significantly reduced from 24.9% to7.2% (p<0.005).
Conclusions—Treatment of Barrett's oesophaguswith omeprazole 20 mg twice daily results in a notable reduction in theexposure of the oesophagus to both acid and duodenal contents. Inaddition, delivery of duodenal contents to the upper gastric body is reduced.

Keywords:bilirubin monitoring; Barrett's oesophagus; omeprazole; pH monitoring; duodenogastric reflux; duodenogastro-oesophageal reflux

     

Lipophilic versus hydrophilic β1 blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction

Objective—To compare the effects of a lipophilic and a hydrophilic β₁ blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction.
Design—Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks.
Setting—Large teaching hospital.
Patients—50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction.
Methods—At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated.
Results—During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol.
Conclusions—At the doses used in this study, atenolol achieved greater β₁ adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of β₁ adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.

Keywords: adrenergic receptors;  myocardial infarction;  stress;  baroreceptors     

Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication

Background—Metronidazole-containing eradicationtherapies are less effective for metronidazole resistantHelicobacter pylori. Although early data suggestedimprovement of the efficacy of bismuth triple therapy after theaddition of acid suppressives, these findings were based on studieswith small numbers of patients, incomplete post-eradication follow up,or omission of pretreatment susceptibility testing.
Aims—To study the efficacy of quadruple therapyin the Amsterdam area, where the efficacy of bismuth triple therapy hasbeen proved to be affected by metronidazole resistance.
Patients and methods—Eighty two consecutivedyspeptic H pylori positive patients with eithermetronidazole susceptible (group I) or metronidazole resistant Hpylori strains (group II) received quadruple therapy for oneweek: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mgfour times a day; tetracycline 500 mg four times a day; metronidazole500 mg three times a day. Susceptibility to metronidazole wasdetermined by the E-test.
Results—Intention to treat analysis showed thatH pylori infection had been cured in 42/43 patients (98%)in group I and 32/39 patients (82%) in group II (p = 0.02).
Conclusion—The efficacy of quadruple therapy issignificantly impaired in patients infected with metronidazoleresistant H pylori. Therefore anon-metronidazole-containing regimen should preferably be used inareas known to have a high prevalence of pretreatment metronidazole resistance.

     

Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study

OBJECTIVE—To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation.
DESIGN—Prospective, randomised, single blind, placebo controlled study.
SETTING—Tertiary cardiac referral centre.
PATIENTS—186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation.
INTERVENTIONS—65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated.
MAIN OUTCOME MEASURES—Recurrence of atrial fibrillation or side effects.
RESULTS—In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol).
CONCLUSIONS—Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.


Keywords: amiodarone; sotalol; atrial fibrillation     

Trial to show the impact of nicorandil in angina (IONA): design, methodology, and management

OBJECTIVE—IONA (impact of nicorandil in angina) is a randomised, double blind, placebo controlled trial that will test the hypothesis that nicorandil (target dose of 20 mg twice daily) will reduce the incidence of cardiovascular events in a cohort of men and women with effort angina and additional risk factors.
METHODS—The primary composite end point of the study is coronary heart disease death, non-fatal myocardial infarction or unplanned hospital admission for cardiac chest pain, and the secondary end point is the combined outcome of coronary heart disease death or non-fatal myocardial infarction. Other cardiovascular outcomes and all cause mortality will also be reported.
RESULTS—More than 5000 subjects have been randomised to receive nicorandil or placebo in addition to normal antianginal treatment. The target population, the assessments made, and the management of the trial are described in detail.
CONCLUSIONS—The IONA study has achieved its first aim of randomising more than 5000 high risk subjects with effort angina. Subject follow up will be complete in the third quarter of 2001.


Keywords: stable angina of effort; cardiovascular events; nicorandil     

Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection

Background—H₂ receptor blockers andproton pump inhibitors reduce intestinal output in patients with shortbowel syndrome.
Aims—To evaluate the effect of intravenousomeprazole and ranitidine on water, electrolyte, macronutrient, andenergy absorption in patients with intestinal resection.
Methods—Thirteen patients with a faecalweight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowellength of 100cm were studied. Omeprazole 40 mg twice daily orranitidine 150mg twice daily were administered for five days in arandomised, double blind, crossover design followed by a three daycontrol period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had noinfluence on the results.
Results—Omeprazole increased medianintestinal wet weight absorption compared with no treatment andranitidine (p<0.03). The effect of ranitidine was not significant.Four patients with faecal volumes below 2.6 kg/day did not respond toomeprazole; in two absorption increased by 0.5-1 kg/day; and in fiveabsorption increased by 1−2 kg/day. Absorption of sodium, calcium,magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged.Four high responders continued on omeprazole for 12-15 months, butnone could be weaned from parenteral nutrition.
Conclusion—Omeprazole increased water absorptionin patients with faecal output above 2.50 kg/day. The effect variedsignificantly and was greater in patients with a high output, but didnot allow parenteral nutrition to be discontinued. Absorption ofenergy, macronutrients, electrolytes, and divalent cations was notimproved. The effect of ranitidine was not significant, possiblybecause the dose was too low.

Keywords:short bowel syndrome; human; diarrhoea; ranitidine; omeprazole

     

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.     

β Blockade in congestive heart failure: persistent adverse haemodynamic effects during chronic treatment with subsequent doses

Objective—To determine whether the acute adverse haemodynamic effects of β blockade in patients with congestive heart failure persist during chronic treatment.
Design—Sequential haemodynamic evaluation of heart failure patients at baseline and after three months of continuous treatment with the β₁ selective antagonist metoprolol.
Setting—Cardiac care unit in university hospital.
Patients—26 patients with moderate to severe congestive heart failure (New York Heart Association grade II to IV) and background treatment with digoxin, diuretics, and angiotensin converting enzyme inhibitors, and with a left ventricular ejection fraction < 25%.
Methods—Baseline variables included a six minute walk, maximum oxygen consumption, and right heart catheterisation. All patients received metoprolol 6.25 mg orally twice daily initially and the dose was gradually increased to a target of 50 mg twice daily. Haemodynamic measurements were repeated after three months of treatment, both before (trough) and after drug readministration.
Results—Long term metoprolol had functional, exercise, and haemodynamic benefits. It produced decreases in heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance, and increases in cardiac index, stroke volume index, and stroke work index. However, when full dose metoprolol was readministered during chronic treatment, there was a reduction in cardiac index (from 2.8 (SD 0.46) to 2.3 (0.38) l/min/m², p << 0.001) and stroke work index (from 31.4 (11.1) to 26.6 (10.0) g.m/m², p < 0.001) and an increase in systemic vascular resistance (from 943 (192) to 1160 (219) dyn.s.cm⁻⁵, p << 0.001).
Conclusions—Adverse haemodynamic effects of β blockers in heart failure persist during chronic treatment, as shown by worsening haemodynamic indices with subsequent doses.

Keywords: heart failure;  β blockers;  adverse effects     

Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone

Background—Malnutrition and growth retardation arecommon complications of Crohn's disease in children. The contributionof resting energy expenditure (REE) to malnutrition is unclear.
Aims—To characterise the REE and body compositionin children with Crohn's disease and compare them with normal controlsand patients with anorexia nervosa; to compare the effects ofprednisolone and enteral nutrition on energy expenditure and body composition.
Subjects—Twenty four children with Crohn'sdisease, 19 malnourished females with anorexia nervosa, and 22 healthycontrol subjects were studied.
Methods—In children with Crohn's diseasemeasurements were done when the disease was acute and repeated at oneand three months after treatment with either prednisolone or enteralnutrition. Resting energy expenditure was measured by indirectcalorimetry and body composition by anthropometry, bioelectricalimpedance analysis, total body potassium,H₂¹⁸O, and bromide space studies.
Results—Body weight and ideal body weight weresignificantly lower in patients with Crohn's disease than in healthycontrols. Lean tissue was depleted and there was an increase inextracellular water. Per unit of lean body mass, there was nodifference between REE in patients with Crohn's disease and controls,whereas patients with anorexia nervosa had significantly reduced REE.With enteral nutrition all body compartments and REE increasedsignificantly (p<0.001). In a subgroup of age-matched men there was asignificant increase in height after three months of enteral nutritioncompared with prednisolone (p<0.01). Those treated with steroids didnot show a significant change in height but did show an increase in allbody compartments. However, intracellular water as well as lean bodymass accretion were significantly higher in the enteral nutrition groupthan in the prednisolone group.
Conclusions—Despite being malnourished, childrenwith Crohn's disease fail to adapt their REE per unit of lean bodymass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone.

Keywords:Crohn's disease; resting energy expenditure; bodycomposition; anorexia nervosa; prednisolone; enteral nutrition

     

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis

BACKGROUND—Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA.
OBJECTIVE—To evaluate the effect of a three month course of ciprofloxacin on ReA.
METHODS—In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery.
RESULTS—Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study.
CONCLUSION—Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

     

Sexual activity as a trigger of myocardial infarction. A case-crossover analysis in the Stockholm Heart Epidemiology Programme (SHEEP)

OBJECTIVE—To investigate sexual activity as a trigger of myocardial infarction and the potential effect modification of physical fitness.
DESIGN—A case-crossover study nested in the Stockholm Heart Epidemiology Programme (SHEEP).
SETTING—Stockholm County from April 1993 to December 1994.
PATIENTS—All patients with a first episode of non-fatal acute myocardial infarction admitted to coronary care units were eligible, and 699 patients participated in an interview.
MAIN OUTCOME MEASURES—Relative risks with 95% confidence intervals.
RESULTS—Only 1.3% of the patients without premonitory symptoms had sexual activity during two hours before the onset of myocardial infarction. The relative risk of myocardial infarction was 2.1 (95% confidence interval (CI) 0.7 to 6.5) during one hour after sexual activity, and the risk among patients with a sedentary life was 4.4 (95% CI 1.5 to 12.9).
CONCLUSIONS—The increased risk of myocardial infarction after sexual activity and the further increase in risk among the less physically fit support the hypothesis of causal triggering by sexual activity. However, the absolute risk per hour is very low, and exposure is relatively infrequent. Thus having sex once a week only increases the annual risk of myocardial infarction slightly. Counselling should focus on encouraging patients to live a physically active life and not on abstaining from sexual activity.


Keywords: myocardial infarction; sexual activity     

Rise in serum C reactive protein after hip and knee arthroplasties in patients with rheumatoid arthritis

OBJECTIVE—Serum C reactive protein (CRP) concentration was evaluated in patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) to ascertain the postoperative CRP response.
METHODS—Thirty seven consecutive patients with RA who had undergone THA or TKA were included in the study. The CRP concentration was measured in every patient once preoperatively and every other day for one week postoperatively.
RESULTS—The peak median CRP concentration (94 mg/l) was achieved on the first and second day postoperatively and was seven times higher than the median preoperative concentration (13 mg/l). CRP declined to the preoperative concentration in about one week. The rise of the CRP concentration was significant (p< 0.001). No infection was encountered in this series.
CONCLUSION—A rapid rise in the postoperative CRP concentration is normal in patients with RA treated by THA or TKA. The CRP concentration decreases to the preoperative value in about one week. Serial CRP measurements, including at least one preoperative measurement, are needed when the clinical significance of the postoperative CRP values is evaluated. When the postoperative CRP concentration remains raised for several days compared with the preoperative value, or even rises, it may indicate the presence of a complication in these patients.