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Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivolung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP‐reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection. In a randomized porcine lung transplant study, the authors demonstrate that ex vivolung perfusion reduces passenger leukocyte transfer from the donor to the recipient, which results in impaired recipient Tcell recruitment to the lung after transplantation.

The project concerns a section of approximately 200 km of the Rio Parana in Argentina. A 1 420 km2reservoir will collect the waters of a 975.000 km2catchment area and will store 16,900 million m3. Two spillways are designed for a flood flow of 95.000 m3/s. A compensating dam will store 2 180 Mm3with a surface area of 800 km2. The operating discharge of the hydropower plant will be between 14.000 and 21.000 m3/s. The paper describes the project and the CARIMA flow model (design, construction, calibration, use).

There has been great interest in Europe in treating selected patients with early-stage breast cancer with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. We review the results of these studies. Five early studies had local recurrence rates of 6% to 37%, reflecting suboptimal patient selection, target definition, and quality assurance procedures. Five more recent studies performed using much more stringent approaches have had recurrence rates of 0% to 7% with 84% to 92% of patients having excellent or good cosmetic results. The 3-year results of a single-institution phase III trial suggest that partial-breast brachytherapy performed in this manner yields local control that is very similar to that of whole-breast irradiation. Recently, a phase III multicenter protocol comparing these 2 modalities has been activated in Europe by the Breast Cancer Working Group of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology. As data from this and other trials mature, they will address and refine issues of patient selection, target volume definition, total dose, and fractionation and hopefully support the implementation of APBI into routine clinical practice.

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local–regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.

In continuing our search for medicinal agents to treat proliferative diseases, we have discovered 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 1, several series of analogues were made that examined the C-6 aryl substituent, a variety of water solublizing substitutents at the C-2 position, and urea or other acyl functionality at the N-7 position. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr;) and nonreceptor (c-Src) classes. Several of the most potent compounds displayed submicromolar inhibition of PDGF-mediated receptor autophosphorylation in rat aortic vascular smooth muscle cells and low micromolar inhibition of cellular growth in five human tumor cell lines. One of the more thoroughly evaluated members, 32, with IC50 values of 0.21 μM (PDGFr), 0.049 μM (bFGFr), and 0.018 μM (c-Src), was evaluated in in vivo studies against a panel of five human tumor xenografts, with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs. Compound 32 produced a tumor growth delay of 14 days against the Colo-205 colon xenograft model.

No abstract.