Percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease using a transluminal endatherectomy catheter (TEC): Initial results and angiographic follow-up

Purpose To evaluate the clinical results of percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease. Methods Rotational atherectomy was performed in 39 patients aged 39–87 years (mean 66.6 years). A total of 71 lesions (43 stenoses and 28 occlusions) were treated in 40 limbs. Additional balloon angioplasty was required in 54% of lesions. Fifteen patients (37.5%) presented in Fontaine stage II, 10 patients (25%) in Fontaine stage III and 15 patients (37.5%) in Fontaine stage IV. Rotational atherectomy at 750 rpm was carried out over a 0.014-inch guidewire with continuous aspiration into a vacuum, bottle. Follow-up angiography and color flow Doppler examinations were performed in 22 patients (23 limbs) after a mean period of 6 months (range 2–14 months) Results There was one primary technical failure. In 36 of 40 lesions there was a good angiographic result with residual stenoses in less than 30%. In 70 lesions treated by rotational atherectomy, however, 54% showed residual stenoses of 30%–50% and these cases required additional balloon angioplasty. The mean ankle-brachial index improved significantly (p<0.001), from 0.49 before the procedure to 1.01 after the procedure. A single distal embolus, related to primary recanalization, occurred and there were two large inguinal hematomas. Cumulative clinical patency after 6 months was 83.8% and cumulative angiographic patency after 6 months was 79.1%. Conclusion Percutaneous rotational atherectomy is a promising approach for the treatment of chronic peripheral vascular disease. Further prospective, randomized studies are necessary to compare percutaneous transluminal angioplasty with this new technical approach.     

Resorptions- und Sekretionsprüfungen bei Perfusion des Rattendarms mit hypo- und hypertonischen Glucoselösungen

Ohne Zusammenfassung     

Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy

Dendritic cells (DC) are increasingly explored as cellular vaccines for tumor immunotherapy. In most reported DC-based cancer vaccine trials, DC have been pulsed with soluble tumor antigen-derived peptide ligands of MHC molecules. Considering that the half-life of peptide/MHC complexes on the cell surface is relatively short and that soluble exogenous protein antigens cannot be efficiently processed via the MHC class I-processing pathway, the current vaccination procedure is not optimal for the induction of strong T cell responses aiming at tumor rejection. Recently, we have shown that antigen presentation can be prolonged when synthetic peptides were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres (MS) for uptake by DC. In the present study, we investigated the phenotypic and functional consequences of MS uptake by human monocyte-derived dendritic cells (MoDC) in vitro. We found that immature MoDC that were prepared in serum free media suitable for clinical application were able to phagocytose high numbers of MS, while matured MoDC showed a reduced capacity for phagocytosis of MS. The ingestion of MS did not change the cell surface expression of CD80, CD83, CD86 and HLA-DR of immature and mature DC, suggesting that MS uptake did not induce DC maturation but that maturation by cytokines or LPS was unaltered in the presence of MS. Furthermore, MS-loaded mature MoDC expressed normal levels of the chemokine receptor CCR7 and migrated as efficiently towards CCL19 or CCL21 as unloaded MoDC. DC viability and the secretion of TNF-alpha and IL-12 was not significantly changed by MS loading. Taken together, our data indicate that PLGA-MS loading has no negative effects on the pivotal properties of MoDC in vitro. It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections and tumors.     

The Kallikrein-Kinin system and muscle metabolism—Clinical aspects

The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients.     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

MR-guided percutaneous nephrostomy of the nondilated upper urinary tract in a porcine model

OBJECTIVE: The purpose of this study was to assess the safety and feasibility of MR-guided percutaneous nephrostomy of the nondilated contrast-enhanced upper urinary tract in a porcine model. SUBJECTS AND METHODS: Six MR-guided percutaneous nephrostomies of the nondilated upper urinary tract were performed in four domestic farm pigs (body weight range, 20-25 kg) using a 0.2-T system. Ten minutes after IV administration of 0.2 mmol/kg of gadodiamide and 0.4 mg/kg of furosemide, a fast T1-weighted sequence was used to guide insertion of an 18-gauge MR-compatible needle into a predetermined calix. After confirmation of needle position using a turbo spin-echo T1-weighted sequence, a 0.035-inch catheter coated with superparamagnetic iron oxide was inserted during MR monitoring. Insertion was followed by tract dilatation and insertion of a 4-French sheath. The final position of the sheath was confirmed by injection of diluted superparamagnetic iron oxide into the collecting system. RESULTS: Needle insertion was successful for all six procedures, with no complications. Instrumentation time ranged from 4 to 13 min (mean, 6+/-4 min). Sheath placement was successful in five of six kidneys. Placement time ranged from 6 to 28 min (mean, 16+/-9 min). CONCLUSION: MR-guided percutaneous nephrostomy of the nondilated contrast-enhanced upper urinary tract in a porcine model is feasible and safe.