Notes: Background and aims : To evaluate the safety, pharmacokinetics and clinical efficacy of the intercellular adhesion molecule-1 antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) at 250–350 mg in Crohn's disease.Methods : Patients (〉 50 kg) with active Crohn's disease (Crohn's disease activity index ≥ 220) were assigned by gender, randomly, to two alicaforsen treatment groups: 300 or 350 mg, infused intravenously three times a week for 4 weeks. All patients weighing 36–50 kg received 250 mg of alicaforsen. Background aminosalicylates, antibiotics, immunosuppressives and corticosteroids were permitted, but tumour necrosis factor-αinhibitors were prohibited. The primary end-point wasclinical remission (Crohn's disease activity index ≤ 150).Results : Twenty-two patients were enrolled with a mean baseline Crohn's disease activity index of 304. Steroids were used by 27%, 5-aminosalicylic acid by 68% and immunosuppressives by 27%; 23% had previously received infliximab. Five subjects withdrew after one to three infusions for infusion-related symptoms. Nine patients (41%) experienced clinical remission. Fifty-three per cent of the evaluable subjects receiving more than three infusions experienced remission (18% at week 8; 29% at week 12). The overall response, using a minimum decrease of 70 in the Crohn's disease activity index, was 41–47% for the evaluable group, at weeks 8 and 12. The median duration of remission was 14 weeks. Plasma pharmacokinetic results showed overlapping levels (Cmax, AUC) for the three doses. The infusion-related reaction profile consisted of fever, chills, headache, nausea, emesis or arthralgias, typically occurring 2–4 h after completion of the first infusion. Reactions were less frequent in patients receiving background corticosteroids. The 2–4-h transient post-infusion partial thromboplastin time prolongation values, a class effect of phosphorothioate oligonucleotides, were 18, 21 and 23 s for 250, 300 and 350 mg, respectively.Conclusions : Alicaforsen (ISIS 2302), at fixed doses of 300 and 350 mg, achieved the desired drug exposure and may be an effective therapy for Crohn's disease. Infusion-related reactions were observed less frequently in patients on corticosteroids, and with decreasing frequency with continued treatment.

Notes: Abstract The dependence of acoustic backscatter variations on sediment grain-size distribution is examined using a combined analysis of 95 kHz side-scan data and approx. 300 grab samples from the New Jersey margin. We show that, under well-controlled circumstances, an unprecedented degree of correlation can be obtained between backscatter intensity and mean grain size. However, backscatter is disproportionately affected by larger grain sizes. Addition of just a few extra weight percentage of the larger grain sizes (〉4 mm), which in our study is typically represented by more abundant shell hash among the older sediments at greater water depths, can completely degrade this correlation.