Chronische Transplantatdysfunktion

Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.     

Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

Pharmacokinetics of high-dose etoposide

The pharmacokinetics of etoposide at doses of 1 gm/m2 to 3 gm/m2 were studied in patients with hematologic malignancies. The noncompartmental systemic clearance, mean residence time, steady-state volume of distribution, and elimination half-life were independent of the dose of etoposide, whereas the AUC was proportional to the dose. Comparison of these results with those reported previously indicates that etoposide exhibits linear pharmacokinetics over a thirtyfold range in doses (0.1 to 3 gm/m2).     

Digital mucoid cyst excision by using the bilobed flap technique and arthroplastic resection

There are a number of proposed causes and treatment approaches for digital mucoid cysts. The described treatment outcomes for this cyst have been variable, with the highest success rate reported with complete excision and single-lobe skin flap closure. This report describes a bilobed flap reconstruction in conjunction with resection of the head of the middle phalanx. A retrospective review was undertaken to evaluate the recurrence rate, complications, and patient satisfaction with this combined procedure. Fifteen patients with an average follow-up of 4.6 years were evaluated. There were no recurrences, flap failures, or other major complications. The use of this flap allows for greater exposure than traditional semi-elliptical incisions while allowing the wide excisional defects to be closed primarily.     

Experimentelle und klinische Studie zur Stabilit?t einer Osteosyntheseplatte für den atrophen Unterkiefer

ZusammenfassungHintergrund Der Anteil an älteren Patienten steigt ständig und damit auch die Zahl traumatischer altersbedingter Verletzungen wie Frakturen des Unterkiefers. Die Frakturversorgung bei älteren Menschen stellt spezielle Anforderungen. Durch das Design einer neu entwickelten Osteosyntheseplatte sollte versucht werden, diese speziellen Gesichtspunkte zu erfüllen.Material und Methoden Im Gegensatz zu den 2.0-Miniplatten (Medartis AG, Basel) besitzt die Pencilbone-2.0-Platte, die aus diesen Miniplatten entwickelt wurde, einen oval geformten Mittelsteg zur Stabilisierung des frakturnahen Knochens und zwei sphärische Gleitlöcher jenseits der Fraktur. An den verstärkten Teil der Osteosyntheseplatte schließen sich jeweils 2 bzw. 3 normale unverstärkte Löcher an, die sich sehr leicht an den frakturfernen Knochen adaptieren lassen. Dies ermöglicht dem Operateur den intraoralen Zugangsweg und eine Handhabung, welche er von der Miniplattenosteosynthese gewohnt ist, bietet aber gleichzeitig eine höhere Stabilität im Vergleich mit den Standard-2.0.-Miniplatten.Ergebnisse und Diskussion Nach experimentellen und biomechanischen Untersuchungen, die alle positive Ergebnisse zeigten, wurde die neue Platte zwischen Oktober 2000 und November 2001 in zwei Kliniken an 16 Frakturen des atrophischen Unterkiefers bei 14 Patienten erfolgreich angewendet. 15 Frakturen heilten primär, lediglich bei einer Fraktur wurde eine neue operative Versorgung wegen Knochendislokation nach erneutem Sturz notwendig.     

A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy.

Selective removal of malignant cells (purging) from bone marrow (BM) is a concern in autologous BM transplantation (ABMT). Use of vincristine, etoposide, or doxorubicin for purging could be rendered ineffective by the presence of multidrug-resistant (MDR) tumor cells. To circumvent this particular problem, we investigated whether 17F9, a monoclonal IgG2b antibody directed against the cell surface product of the MDR gene, P-glycoprotein, is effective in selective removal of MDR cells from BM when used with rabbit complement (C'). Using two different cell lines we have demonstrated that 17F9 + C' selectively lyses MDR-positive cells. Three rounds of antibody + C' resulted in 96.4% +/- 3.6% kill of K562/DOX and 100% +/- 0% of CEM/VLB cells. Mixtures of malignant cells and normal BM resulted in 99.85% removal of K562/DOX and 99.91% removal of CEM/VLB clonogenic cells. This treatment did not affect normal committed precursors compared with C' alone. The addition of the cytotoxic agent etoposide (VP-16) following antibody purging results in a 4.6 log reduction of malignant cells. Furthermore, this antibody was effective when used against patients' leukemic blasts. These results suggest the use of 17F9 + C' is effective and selective for removal of MDR cells from BM before ABMT and the addition of VP-16 enhances the purging efficacy.