Rituximab-cyclophosphamide-dexamethasone combination in the management of autoimmune cytopenias associated with chronic lymphocytic leukemia.

We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders (AIDs) in 48 chronic lymphocytic leukemia (CLL) patients. Overall, 81% of patients were relapsing for AID after previous treatment with corticosteroids, splenectomy, rituximab or alemtuzumab. Diagnosis of AID was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenia (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 patients (10.5%). Median time of autoimmune disorder (AID) onset from CLL diagnosis was 60 months (range: 0-240), and CLL was considered progressive in 40% of subjects upon AID diagnosis (complex AID). Median hemoglobin pre-treatment was 7.7 g/100 ml, and median platelet count 36.5 × 10(9)/l, returning to a median of 12.5 /100ml and 37.5 × 10(9)/l, respectively. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). Median duration of response for autoimmunity (DR-AI) was 24 months, but DR-AI was higher for patients presenting: (1) AID early during CLL course (<3 years), or (2) both PRCA and AIHA. Median time to CLL progression in 48 patients was 16 months, but this time was statistically shorter for Evan's syndrome and AITP patients as compared with AIHA and PRCA patients. This study emphasizes the relevance of CLL-directed immune chemotherapy in the management of CLL-associated AID.

Study of catheter designs and drug mixing processes using 2D steady numerical simulations.

The effectiveness of substance delivery through catheters is an important issue in interventional radiology, especially for infusion therapies where the pharmacokinetic advantage of local intra-arterial drug administration has been firmly established. In principle, the procedure is used to provide appropriate local concentrations while maintaining low systemic values so as to minimise the global effect and toxicity of the intervention. However, poor drug mixing may produce excessive local concentrations potentially damaging for the surrounding tissues and may lead to unsuccessful therapies. These phenomena have been observed in the infusion therapies of liver cancers through the hepatic artery and with brain tumour therapies through the carotid artery. Many aspects of the drug delivery methodology have been explored in order to determine the infusion conditions that would provide optimal mixing: the catheter tip design is considered one of the most important characteristics to be investigated for this purpose. Interestingly, it turns out that angiographic procedures could also benefit from this, because better mixing properties are associated with designs that provide potentially less harmful flow conditions such as jets, whipping and recoil of the catheter on the vascular wall. A 2D steady numerical model is proposed, to simulate the main physical processes occurring during catheter substance infusion: blood dynamics is taken into account with the Navier-Stokes equations and substance dispersion by the flowing blood with the advection-diffusion equation. The model is used to evaluate mixing properties of certain catheter designs in different flow conditions. In particular, two types of side hole catheter are compared in the context of water bath injection and in the context of vessel injection. The simulations suggest that the improved mixing reported with water bath experiments would not be maintained in the clinical context of arterial circulation.

[Not Available]. / Son de blé et laxatifs: étude comparative chez des personnes âgées.

Constipation is an important problem in older patients, who are often chronic users of laxatives. Dietary fiber is becoming more important in treating gastrointestinal disorders. In studying the drug profiles of 52 elderly patients in a chronic care unit, we found that a large percentage were taking laxatives. We therefore wanted to compare the effect of a diet enriched with bran to the effect of an emollient laxative, docusate sodium. Patients were divided into two groups. For the first three weeks, one group received a diet with 15 g/day natural wheat bran added, plus a placebo, and the other received 200 mg/day docusate sodium. In the second three weeks, the groups were switched to the other treatment. After the 42 days of the study, the number of stools per day per patient did not differ significantly, whether they had been taking bran or laxatives. Otherwise, transit times revealed that those who had taken bran had a more rapid transit time than those who had taken laxatives. These results show the efficacy of dietary fiber, particularly wheat bran, in prevention and correction of constipation in the elderly.