No abstract

Monocytes are key players in atherosclerotic. Human monocytes display a considerable heterogeneity and at least three subsets can be distinguished. While the role of monocyte subset heterogeneity has already been well investigated in coronary artery disease (CAD), the knowledge about monocytes and their heterogeneity in peripheral artery occlusive disease (PAOD) still is limited. Therefore, we aimed to investigate monocyte subset heterogeneity in patients with PAOD. Peripheral blood was obtained from 143 patients suffering from PAOD (Rutherford stage I to VI) and three monocyte subsets were identified by flow cytometry: CD14++CD16− classical monocytes, CD14+CD16++ non-classical monocytes and CD14++CD16+ intermediate monocytes. Additionally the expression of distinct surface markers (CD106, CD162 and myeloperoxidase MPO) was analyzed. Proportions of CD14++CD16+ intermediate monocyte levels were significantly increased in advanced stages of PAOD, while classical and non-classical monocytes displayed no such trend. Moreover, CD162 and MPO expression increased significantly in intermediate monocyte subsets in advanced disease stages. Likewise, increased CD162 and MPO expression was noted in CD14++CD16− classical monocytes. These data suggest substantial dynamics in monocyte subset distributions and phenotypes in different stages of PAOD, which can either serve as biomarkers or as potential therapeutic targets to decrease the inflammatory burden in advanced stages of atherosclerosis.

From July 1986 to July 1989, 40 patients (92% pretreated) with deep-seated, advanced soft tissue sarcomas (STS, 25 patients), Ewing's sarcomas (ES, eight patients), osteosarcomas (OS, three patients) and chondrosarcomas (ChS, four patients) were treated at the University of Munich in a protocol involving regional hyperthermia (RHT) combined with ifosfamide plus etoposide. A total of 265 RHT treatments (mean, 6.6 RHT per patient) were applied including 33 pelvic, four extremity, and three abdominal sites. The mean tumor volume was 537 cc (range, 50 to 2,980 cc). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1 to 5), etoposide (100 mg/m2, days 1, 3, and 5), and mesna (300 mg/m2 x 4, days 1 to 5) with RHT given only on days 1 and 5 in repeated cycles every 4 weeks. Acute toxicity consisted primarily of pain (57%) combined with local discomfort within the annular phased array applicator (AA) of the BSD hyperthermia system (BSD Medical Corp, Salt Lake City, UT). The average maximum systemic temperature was 37.4 +/- 0.5 degrees C, and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. Detailed thermal mapping by invasive thermometry was performed in all patients. In 38 assessable patients, the overall objective response rate was 37%: six complete responses (CRs), four partial responses (PRs), and four favorable histologic responses (FHRs) (95% confidence limits, 22% to 54%). Complete responders are alive and disease-free at 40, 35, 23, 19, 19, and 8 months. Of patients with PR and FHR, two died from metastatic disease after 4 and 17 months and one died from other disease after 27 months. The remaining five patients are stable at 37, 25, 21, 13, and 8 months. Eleven patients showed no change (NC), and 13 patients showed local tumor progression (PD). The mean observation time for all patients was 11.6 months. The time-averaged temperatures (Ts) of all RHT treatments calculated as 20% (T20), 50% (T50), or 90% (T90) of measured tumor sites differed significantly between responders and nonresponders (T20, P = .003; T50, P = .006; and T90, P = .004; respectively). These data support activity for ifosfamide-etoposide combined with RHT in pretreated patients with advanced sarcomas.