RESUMO
Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (µAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the µl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 µm tall artificial capillaries, and a 66 µm thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O2, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.
RESUMO
4'-O-Tetrahydropyranyl adriamycin (THP adriamycin) is a new anthracycline active as a single drug in advanced breast cancer. We have undertaken a phase II study as first-line treatment for metastatic disease with THP adriamycin day 1 = 40 mg/m2 i.v. bolus and 5-fluorouracil day 1 to day 5 = 750 mg/m2 as a continuous i.v. infusion. The dose of THP adriamycin was further escalated up to the maximal tolerated dose defined as grade 3 granulopenia for each patient. Thirty-nine patients were included, 37 being so far evaluable for toxicity and for efficacy. The mean number of cycles given was 5 (range: 2-12). The overall response rate (CR + PR) was 54% (95% CI: 37.9-70.1) and the CR rate 8%. Sites of response were as follows: lung 6/9, liver 11/18, breast 4/8, nodes 7/14, skin 3/8, bone 2/8. Neutropenia with grade 3 + 4 nadir values was observed in 70.2% of the patients according to the objective of the study. No severe thrombopenia or anemia occurred. Stomatitis grade 3 was seen in 27% and grade 4 in 3% of the patients. Alopecia grade 2 was seen in 18% and grade 3 in 9%. No other toxicity was observed. We conclude that this association is effective in metastatic breast cancer, giving few alopecia. A high response rate in liver metastases warrants further evaluation.
