Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Is your patient taking the medicine? A simple assay to measure compliance with 5-aminosalicylic acid-containing compounds.

BACKGROUND: Poor compliance with 5-aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5-aminosalicylic acid; however, the chemical similarity between 5-aminosalicylic acid and salicylate might provide a solution. AIM: To determine the feasibility of using salicylate levels to monitor compliance with 5-aminosalicylic acid medication. METHODS: Thirty-six patients with inflammatory bowel disease, taking maintenance 5-aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5-aminosalicylic acid and its metabolite, N-acetyl-5-aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated. RESULTS: Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 microg/mL. The correlations between urinary salicylate and 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid were 0.96 (95% confidence interval, 0.91-0.98) and 0.9 (95% confidence interval, 0.77-0.96), respectively. Sixteen biopsies were available from 13 patients. The 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid concentrations were 0.2-657 ng/mg and 1.6-1598 ng/mg, respectively; there was no correlation with bowel salicylate. CONCLUSIONS: The close correlation between 5-aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5-aminosalicylic acid therapy.

Pseudo myocardial infarction and pseudo ventricular hypertrophy ECG patterns in Wolff-Parkinson-White syndrome.

In Wolff-Parkinson-White (WPW) syndrome, the ventricles are pre-excited through an accessory conduction pathway, bundle of Kent, which directly connects atria with ventricles bypassing the atrioventricular node. The altered sequence of ventricular activation secondary to presence of the bundle of Kent may cause pseudo myocardial infarction and pseudo ventricular hypertrophy patterns on electrocardiogram. The morphology of these pseudo electrocardiographic patterns depends on the anatomical location of the bundle of Kent around the circumference of the atrioventricular ring. Electrocardiograms of the WPW syndrome displaying morphology of different pseudo patterns are presented and the mechanisms causing pseudo patterns are reviewed.

Pseudo ventricular hypertrophy and pseudo myocardial infarction in Wolff-Parkinson-White syndrome.

In Wolff-Parkinson-White syndrome, the sequence of ventricular activation is altered and depending on the anatomic site of the accessory conduction pathway may result in pseudo ventricular hypertrophy and pseudo myocardial infarction patterns on electrocardiogram. The right-sided accessory pathway may direct the depolarization vector towards left amplifying R-wave amplitude in left-sided limb-leads simulating left ventricular hypertrophy. The left-sided accessory pathways may give rise to prominent R-waves in right precordial leads simulating right ventricular hypertrophy. The right lateral accessory pathways may simulate anterior infarction because of prominent Q-waves in right precordial leads. The left lateral accessory pathways directing depolarization vector towards right may cause Q-waves in lateral limb-leads simulating high lateral myocardial infarction. In posteroseptal accessory pathway, the ventricular depolarization vector is directed superiorily giving rise to prominent Q-waves in inferior limb leads simulating inferior myocardial infarction. Therefore, ventricular hypertrophy and myocardial infarction should not be diagnosed from the electrocardiograms of Wolff-Parkinson-White syndrome.