Immunotherapy for viral and fungal infections.

Allogenic stem cell transplantation (allo-SCT) represents the only curative option for several hematological malignancies. Due to a delayed and dysfunctional immunological recovery infectious complications and residual tumor cells following allo-SCT are still major causes of failure of this procedure. Here we discuss the most common infectious complications of allo-SCT and describe current and future strategies to prophylaxe or treat these complications using novel immunotherapeutic strategies.

[Urological rehabilitation of spinal cord injury patients]. / Urologische Rehabilitation Querschnittgelähmter.

The urological rehabilitation of spinal cord injury patients depends on an optimal urological treatment plan and good cooperation between the patient, general practitioner, urologist, and a centre that specialises in treating spinal cord injuries. Because of medical advancements in neuro-urology, one can assume that in cases of lifelong urological care, the individual's life expectancy will be almost normal. The recognition that nonphysiological bladder storage pressure results in restricted kidney function has led to various therapeutic strategies with complementary goals, such as protection of the upper urinary tract, urinary continence, individualized bladder management.

[Single-use intermittent catheterisation]. / Der intermittierende Einmalkatheterismus.

In patients with bladder dysfunctions, intermittent catheterisation is a bladder evacuation technique with a low complication rate. Therefore, it is regarded as the method of choice in the treatment of chronic residual urine, mostly due to a hypo- or acontractile detrusor. Regarding the incidence of urinary tract infections and urethral strictures, aseptic catheterisation seems to be superior to the clean technique. There are, however, no independent, prospective, controlled, randomised, double-blinded studies comparing the different catheter types. Thus, the question of which catheter is the ideal one cannot be answered yet. Predominantly in patients who have to perform intermittent catheterisation for good, the prevention of long-term complications, especially of the upper urinary tract, is of the utmost importance. In the long run, using an inadequate technique and catheters not optimally designed will clearly lead to a higher complication rate. Despite the lower prices of certain catheters, treatment of these complications will lead to higher instead of lower costs. The data available today clearly demonstrate that aseptic intermittent catheterisation is the technique of choice today. Important details of this treatment modality, however, have to be elucidated by prospective studies in the future.

[Intravesical therapy for overactive bladder]. / Intravesikale Therapie der überaktiven Blase.

INTRODUCTION: Despite recent advances in the field of anticholinergic drugs, lack of efficiency and side effects are still the main reasons for discontinuation of treatment. The introduction of botulinum A toxin was a milestone in the treatment of detrusor overactivity. The treatment, however, is invasive, the duration of the treatment effects is limited, and long-term results are not yet available. The following addresses therapeutic alternatives to local treatment of overactive bladder. MATERIALS AND METHODS: A total of 52 patients received intravesical oxybutynin. In 16 patients, capsaicin was instilled in the bladder and 28 patients were treated with EMDA. RESULTS: Intravesical oxybutynin was successful in 86%; the success rate of capsaicin instillation was 47%. EMDA was successful in 78%. Two transient ischemic attacks following EMDA were observed as significant side effects. CONCLUSION: Besides botulinum A toxin, several effective treatment options are available for patients with detrusor overactivity refractory to oral anticholinergic treatment. Therefore, in each individual patient, possible risks and complications of the different treatment options should be considered thoroughly to find the optimal method in each case.

Induction of CMV-specific T-cell lines using Ag-presenting cells pulsed with CMV protein or peptide.

BACKGROUND: CMV disease is still associated with a high morbidity and mortality in recipients of a solid organ or stem cell graft, especially in patients undergoing allogenic stem cell transplantation. Reconstitution of CMV-specific CD4(+) and CD8(+) cytotoxic T cell responses are essential to control CMV infection following allogenic stem cell transplantation. The transfer of unselected populations of lymphocytes from the peripheral blood of a CMV-scropositive donor to a transplant recipient can be used to control CMV infection. However, such transfer of unselected donor lymphocytes is limited by potentially fatal complications that arise from alloreactive T cells, also present in the unselected donor lymphocytes. Thus to make infusion of donor T cells safe and also more effective in controlling CMV infection in the recipient of the T cell infusion, T cells are manipulated in vitro to deplete alloreactive T cells and to enrich for CMV-specific T cells. METHODS: Using various antigen-presenting cells (monocytes/PBMNCs/dendritic cells) and different modes of antigen presentation (infected APCs, pulsing of protein or peptide antigen) different CMV-specific T cell populations can be generated and expanded. RESULTS: Using protein-/or peptide-pulsed DCs CMV-specific CD8(+) cytoxic T cell lines (can be generated and expanded) in addition CMV-specific CD4(+) T cell lines can be generated when CMV-protein-pulsed DCs are used as antigen-presenting cells. When peripheral blood mononuclear cells were stimulated with CMV lysates predominantly CMV-specific CD4(+) T cells are generated and expanded ex vivo. DISCUSSION: Depending on the APC used (monocytes versus DC) and the mode of antigen presentation (protein versus peptide pulsing) different CMV-specific T cell populations of varying purity can be generated which show preserved function when tested for specific proliferation, cytokine production and cytotoxicity.

Ex vivo generation of human cytomegalovirus-specific cytotoxic T cells by peptide-pulsed dendritic cells.

Adoptive transfer of donor-derived human cytomegalovirus (HCMV)-specific T-cell clones can restore protective immunity after stem cell transplantation. Ex vivo induction of HCMV-specific T cells using HCMV-infected fibroblasts as stimulator cells confines this approach to HCMV-seropositive donors and requires the presence of infectious virus during the stimulation procedure. In this study, we describe a potential alternative strategy to generate HCMV-specific T cells ex vivo for adoptive immunotherapy. Generation of HCMV-specific cytotoxic T lymphocytes (CTLs) ex vivo was investigated using peptide-pulsed dendritic cells as antigen-presenting cells. HCMV-specific T cells were generated and sufficiently expanded for adoptive immunotherapy in 6 out of 14 HCMV-seropositive and 2 out of 11 HCMV-seronegative donors. The CTLs recognized HCMV-infected autologous fibroblasts. No lysis was observed with either non-infected autologous or HLA-mismatched infected fibroblasts. Staining with tetrameric HLA/peptide complexes revealed significant enrichment for peptide-specific T cells of up to 28% and > 90% of CD8(+) T cells after three and five specific stimulations respectively. In addition, the expansion rates indicated that ex vivo generation of > 1 x 10(9) HCMV-specific T cells was possible after 6--7 weeks when cultures were initiated with 1--5 x 10(6) responder cells. Thus, the approach with peptide-pulsed DCs to generate HCMV-specific CTLs is feasible for clinical application after allogeneic stem cell transplantation.

[Ileal conduit bleeding in portal hypertension. A rare complication]. / Ileumconduitblutungen bei portaler Hypertonie. Eine seltene Komplikation.

The ileal conduit is a simple and safe supravesical urinary diversion with few postoperative complications. In patients with liver disease with portal hypertension, however, the risk of recurrent, peracute conduit bleeding is increased. While the diagnosis is simple, several therapeutic options are available. In most cases the bleeding comes from stomal varices, that can be controlled with local sclerotherapy with 3% Ethoxyscerol or ligation of the bleeding vessel. The resection of the part of the conduit carrying the varices is an option if bleeding is life threatening or the source cannot be localised. If bleeding recurs excision of the conduit should be considered. Malignant disease must be excluded as a bleeding source.

[Therapy of abdominal neuroblastoma in Essen]. / Die Therapie des abdominellen Neuroblastomas in Essen.

Between 1980 and 1996, 74 children aged between 3 and 148 months were operated for neuroblastomas at the University Clinic Essen. A total of 44 patients had a neuroblastoma stage 4, 11 a stage 3, nine a stage 2, two a stage 1, and eight a stage 4s. If there was doubt about the possibility of a primary resection of the tumor, chemotherapy was carried out before surgery. This procedure enabled a complete local resection of the tumor in 46 children. In the postoperative course 29 children died, 25 of which presented tumor progress; four died of complications following bone marrow transplantation. Two children are currently being treated for tumor recurrence, while 43 have survived without tumor recurrence for 15 years. Complete tumor resection produced a better survival rate. If there is any doubt in the primary possibility of complete tumor resection a reduction of the tumor mass can be achieved by chemotherapy. This allows radical surgery can be achieved in significantly more cases.