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Biomedical subjects

U Wetterauer

Publications and source records attributed to U Wetterauer.

At least 19 recordsLinked to original sources
PubMed2006

A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells.

Prostate cancer is the most commonly diagnosed form of cancer and the second leading cancer-related death among men in the Western civilization. Since no effective therapy exists for this tumor after progression beyond resectable boundaries, there is an urgent need for new treatment strategies. Prostate specific membrane antigen (PSMA) represents an excellent target on prostate cancer cells, and therefore specific immunotherapy may be a novel therapeutic option for the management of this tumor. We constructed a fully recombinant immunotoxin (A5-PE40) from a single-chain antibody fragment (scFv) against cell-adherent PSMA and a truncated form of Pseudomonas exotoxin A (PE40) lacking its natural binding domain Ia. The scFv A5 was obtained from a mAb elicited with native PSMA by phage display technology and direct selection on cells carrying the antigen. The bacterially expressed and purified immunotoxin A5-PE40 specifically binds to PSMA-positive prostate cancer cells and induces a 50% reduction of viability (IC50) at a concentration of 20 pM, while PSMA-negative cells remain unaffected. Due to its high and specific toxicity this recombinant immunotoxin is a promising candidate for therapeutic applications in patients with prostate cancer.

ADP Ribose Transferases↗
PubMed2001

Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary bladder carcinogenesis in a rat model.

BACKGROUND: The objective of this study was to determine the effect of intravesically applied, recombinant, galactoside specific mistletoe lectin (rML) on chemically induced tumor development in the urinary bladder of rats. METHODS: For tumor induction, rats were treated with four biweekly 1.5 mg doses of N-methyl-N-nitrosourea (NMU) intravesically (Weeks 0, 2, 4, and 6). The control group (n = 39 + 17 rats) received no other treatment. The four therapy groups also received rML twice weekly according to one of the following instillation regimens: 1) 30 ng rML per instillation from Week 8 to Week 13 (Group a: n = 14 rats), 2) 150 ng rML per instillation from Week 8 to Week 13 (Group b: n = 23 + 15 rats), 3) 30 ng rML per instillation from Week 14 to Week 19 (Group c: n = 22 rats), and 4) 150 ng rML per instillation from Week 14 to Week 19 (Group d: n = 19 rats). After the rats were asphyxiated at Week 21, the urinary bladders were excised in toto and examined histopathologically. To study the immunomodulatory effects of intravesically applied rML, 17 animals from the control group and 15 animals from Group b were asphyxiated at Week 13, and urinary bladder tissue was analyzed by semiquantitative reverse transcriptase-polymerase chain reaction analysis for mRNA expression of interferon-gamma, interleukin-10, and Fas ligand. RESULTS: By Week 21, atypical hyperplasia and neoplastic transformation were found in 82% of the animals in the control group. In contrast, in all four cohorts that were treated with rML, significantly lower rates of atypical hyperplasia and neoplastic transformation were found (Group a, 50%; Group b, 52%; Group c, 45%; and Group d, 42%). By Week 13, in the bladder tissue of 15 rML-treated animals from Group b, lower expression of interleukin-10 mRNA was measured, whereas the expression levels of interferon-gamma mRNA and Fas ligand mRNA were comparable to those of 17 animals from the control group. CONCLUSIONS: The current data provide evidence for an inhibitory effect of rML on experimental urothelial carcinogenesis that does not seem to be due to interferon-gamma and/or interleukin-10 dependent mechanisms.

Adjuvants, Immunologic↗
PubMed2001

[Prescribing of sildenafil by national insurance program physicians. What basic sexual medicine qualification is required?].

The role of sildenafil in the treatment of erectile dysfunction is discussed. Especially in primary care there is a necessity to weigh the individual cost-benefit-ratio. Functional analysis of erectile dysfunction, exclusion of psychiatric and organic comorbidity, identification of sexual deviance and couple counseling about the advantages and disadvantages of sildenafil prescription are the core prerequisites of sildenafil application in primary care. The counseling model of PLIS-SIT is proposed as a guideline for counseling process. Current approaches of education for general practitioners are reviewed and the integration in a recently developed training for management of psychiatry and psychosomatic illness in general medical settings is proposed. Finally open questions for research and quality management are discussed.

Cost-Benefit Analysis↗
PubMed2001

Reconstruction of seminal ducts in obstructive azoospermia.

Depending on the localization of the obstruction of the seminal ducts, either a microsurgical reconstruction (tubulovasostomy, vasovasostomy) or a transurethral resection of the ejaculatory ducts is carried out. We have compared the effectiveness and economic advantages of reconstructive microsurgery of the epididymis and vas deferens with standard procedures in animal experiments. Microsurgical invagination techniques in tubulovasostomy are equal to the standard procedure from the point of view of the patency and fertility rates. They are also easier to learn and carry out. Less time is required for the invagination technique, and also less microsurgical suture material. The double-layer technique in vasovasostomy is equal to the one-layer microsurgical technique from the point of view of patency and fertility rates. The one-layer technique requires less time and suture material. It seems that the discrepancy between the patency and the fertility rate is related to immunological processes after reconstruction of the seminal ducts. In cases of obstructive azoospermia it is necessary to investigate the individual conditions and possibilities of the infertile couple. As a result of the high success rate obtainable today by surgical reconstruction of the seminal ducts, this must constitute the first type of treatment to be considered, before any of the procedures of reproductive medicine are undertaken.

Animals↗
PubMed2000

Comparison of the activation status of tumor infiltrating and peripheral lymphocytes of patients with adenocarcinomas and benign hyperplasia of the prostate.

BACKGROUND: The presence of lymphocytic infiltration in prostate carcinomas has been shown to have prognostic relevance. However, it is not yet clear if this infiltrate represents a tumor-specific activated cell population or not. Therefore, the aim of the present study was to characterize the activation status of freshly isolated tumor infiltrating lymphocytes (TIL) from prostate carcinomas (PCa) and benign hyperplasia (BPH) with respect to the mRNA expression of cytokines and apoptotic factors. METHODS: TIL were isolated from mechanically disaggregated tumor material by gradient centrifugation. The cells of the interphase were depleted from epithelial cells with anti-human epithelial antigen magnetic beads and then CD3(+)- lymphocytes were selected with magnetic beads against this determinant. In these pure lymphocyte preparations the mRNA expression of IL-1, IL-10, IFN-gamma, TNF-alpha, Fas and Fas ligand was determined by using a semiquantitative RT-PCR. Contamination with tumor cells was excluded by a PCR for PSA and PSMA. RESULTS: The CD3(+)-TIL from 21 patients with PCa and 20 patients with BPH expressed significantly higher levels of IL-10- and Fas ligand-mRNA compared to the autologous CD3(+)- PBL, whereas the expression of IL-1-, TNF-alpha- and Fas-mRNA was not different in either cell population. In contrast, the mRNA levels of IFN-gamma were significantly higher only in the CD3(+)-TIL from the carcinomas but not from the BPH compared to autologous CD3(+)-PBL. CONCLUSIONS: Since high levels of IFN-gamma have been reported to be produced by specifically lytic lymphocytes, our results suggest the presence of specifically activated TIL in the prostate carcinomas but not in the BPH, whereas inflammatory activated TIL are present both in the carcinomas and the BPH.

Adenocarcinoma↗
PubMed2000

Biological effects of natural and recombinant mistletoe lectin and an aqueous mistletoe extract on human monocytes and lymphocytes in vitro.

Mistletoe lectin is thought to constitute the active principle in extract preparations from mistletoe, which are widely used as immunomodulators in adjuvant tumor therapy. However, no study exists which compares the immunological potency of different well-defined mistletoe lectin preparations on human immune cells. Therefore, in the present study the biological effects of an aqueous mistletoe extract, standardized for mistletoe lectin I (eML), the isolated natural mistletoe lectin (nML), and the recombinant form of this lectin (rML) on human peripheral blood monocytes and lymphocytes were compared with respect to cell viability and cytokine induction. After 48-hr incubation of peripheral blood mononuclear cells (PBMC) with rML, nML, and eML, a continuous concentration-dependent decrease in cell viability was found with an IC50 of about 3 ng/ml for rML and nML and 10 ng/ml for eML, respectively. This effect also was seen when isolated lymphocytes and monocytes were separately incubated with the lectin preparations. After incubation of PBMC and isolated monocytes of 5/10 blood donors with eML, an increase in cell viability was found at lectin concentrations between 10 and 1,000 pg/ml. This effect was not seen with the pure lectin preparations nML and rML. After 48-hr incubation of PBMC with rML, nML, and eML, induction of IL-1-beta, TNF-alpha, IL-2, IL-6, and IL-10 but not IFN-gamma was measured. For IL-1-beta it could be shown that cytokine induction took place at a broad lectin concentration range (0.1-100 ng/ml). Cytokine levels varied greatly in the PBMC cultures of the different blood donors. When monocytes were separately incubated with eML, nML, and rML for 48 hr, high levels of IL-1-beta were found. In contrast, in cultures of separated lymphocytes from the same donors only a minimal production of IL-1-beta and no production of IFN-gamma was found after incubation with rML, nML, and eML. It is concluded that there are quantitative differences in the immunomodulatory effects of the mistletoe lectin preparations on human monocytes and lymphocytes. Therefore, measurement of cell viability and cytokine induction may be a diagnostic laboratory tool to determine the immunological potency of various mistletoe preparations and may help to clarify the clinical benefit of therapies with these substances.

Adult↗
PubMed2000

Intravesical administration of 5-aminolevulinic acid (5-ALA). Safety and pharmacokinetics of 5-ALA and its metabolite protoporphyrin IX.

OBJECTIVE: In an open study, the local and systemic side effects and pharmacokinetics of 5-aminolevulinic acid (5-ALA) and the fluorescent metabolite protoporphyrin IX (PPIX) were investigated after intravesical administration for the fluorescent photodetection of superficial bladder carcinoma. PATIENTS AND METHODS: In 20 patients with confirmed bladder carcinoma, 5-ALA was introduced into the bladder 2 h (15 patients) and 4 h (5 patients) before an elective endoscopic resection. The 5-ALA and PPIX levels in the plasma were determined before and up to 10 h after application, and in the urine 2 h or 4 h after application. RESULTS: The plasma level of 5-ALA rose rapidly, the maximal concentration (340 ng/ml) being reached in 0.55 h (2 h) or 0.62 h (4 h). The elimination half-life of 5-ALA amounted to 0.74 h (2 h) or 0.79 h (4 h). In five of the patients, there was a measurable plasma concentration which ranged from the detection limit of 4.3 ng/ml to 14 ng/ml between 2 h and 5 h after application, and then fell below the detection limit after 9 h. Absorption of 5-ALA by the bladder was low, i.e. less than 1% of the total amount applied. During a period of observation of 96 h, no 5-ALA-specific side effects appeared. CONCLUSION: Because of the small quantity of 5-ALA resorbed following its intravesical administration, only minimal concentrations of PPIX that are responsible for producing side effects can be metabolised in the plasma. Therefore, no systemic side effects are to be expected after the intravesical administration of 5-ALA.

Administration, Intravesical↗
PubMed2000

Enhanced expression of IFN-gamma mRNA in CD4(+)or CD8(+)tumour-infiltrating lymphocytes compared to peripheral lymphocytes in patients with renal cell cancer.

The mRNA expression of the cytokines IFN-gamma, IL-10 and TNF-alpha and the proapoptotic factor Fas ligand (FasL) was compared in freshly isolated CD4(+)and CD8(+)tumour-infiltrating lymphocytes (TIL) and simultaneously obtained autologous CD4(+)and CD8(+)peripheral blood lymphocytes (PBL) from 20 patients with renal cell carcinomas (RCC). TIL were isolated from mechanically disaggregated tumour material and PBL from peripheral blood by gradient centrifugation. The cells of the interphase were depleted from tumour cells with anti-human epithelial antigen magnetic beads and then positive selection was performed with anti-CD4 or anti-CD8 magnetic beads. In these pure lymphocyte preparations the constitutive expression of cytokine and FasL mRNAs was determined by using a PCR-assisted mRNA amplification assay. In the CD4(+)TIL from the 20 patients with RCC, levels of mRNAs encoding for IFN-gamma (P</= 0.001), IL-10 (P</= 0.05), and FasL (P</= 0.001) were significantly higher than in the autologous CD4(+)PBL. Comparison of CD8(+)TIL and CD8(+)PBL revealed a significant higher expression of IFN-gamma (P</= 0.001), IL-10 (P</= 0.01) and FasL mRNAs (P</= 0.001) in the former. However, TNF-alpha mRNA levels were significantly lower in the CD8(+)TIL than in the CD8(+)PBL (P</= 0.05). These data reflect a general in vivo activation of RCC infiltrating lymphocytes in the tumour surrounding.

Adenocarcinoma, Clear Cell↗
PubMed2000

Systemic and local immunomodulatory effects of intravesical BCG therapy in patients with superficial urinary bladder carcinomas.

PURPOSE: The aim of the present study was to elucidate whether only local, or also systemic immunomodulatory effects may be induced by intravesical BCG therapy of superficial urinary bladder cancer. MATERIALS AND METHODS: A total of 37 patients with stages Ta to T1b superficial transitional cell bladder carcinomas received 6 weekly BCG instillations after transurethral resection of the tumor. In a first group of 19 patients blood was taken before each BCG instillation and 6 weeks after the last one. In a second group of 18 patients blood and urine was taken before and 2, 6, and 24 hours after each BCG instillation. In the mitogen-stimulated whole blood cell cultures and in the urine samples the levels of the cytokines IL-1beta, IL-2, IL-10, TNF-alpha and IFN-gamma were determined by enzymoimmunological tests. Additionally, in all plasma and urine samples the levels of TNF-p75-receptor (TNF-p75-R) were measured. RESULTS: Comparison of ex vivo leukocyte cytokine production in the blood cell cultures of the patients of group I revealed no significant change in the levels of the cytokines. In contrast, TNF-p75-R plasma levels increased significantly during the experimental time of 12 weeks (p < or =0.01). In the blood cell cultures of the group II patients a different daytime variation of cytokine production was seen, compared to the 19 healthy controls. After BCG instillation the normal peak cytokine production in the evening was suppressed. A significant rise in plasma TNF-p-75-R levels was measured 24 hours after BCG instillation (p < or =0.05). In the urine of these patients significantly higher levels of all measured cytokines and TNF-p75-R were observed 6 to 24 hours after the instillation. CONCLUSIONS: The results suggest that besides the well known local immune activation, BCG instillation also leads to a modulation of peripheral immune mechanisms.

Adjuvants, Immunologic↗
PubMed1999

[Limitations of reproductive medicine from an andrological/urological point of view].

Since the first child was born after in-vitro fertilization in 1978, different techniques of ovarian stimulation, oocyte retrieval and embryo culture have improved significantly. The development of microinjection techniques was a mile stone in reproductive medicine. Even in cases of severe impairment of semen quality, using the Intracytoplasmic Sperm Injection (ICSI), pregnancy rates of approximately 20 % per treatment cycle can be achieved. However for using artificial reproductive techniques (ART) the female age is a major limiting factor as well as the development of premature ovarian failure (POF). Crucial for the male is the question whether or not sperm cells can be retrieved. Today an interdisciplinary approach is recommended to take care of the afflicted couple in order to address the complex problem of infertility. There is evidence that children born after microinjection techniques bare a higher risk for chromosomal aberrations compared to the normal population. However rates of major malformations seem to be identical in both groups. An evaluation of the potential risks and efforts and an extensive counseling of the infertile couple has to be taken before initiating invasive ART.

Chromosome Aberrations↗
PubMed1999

Microsurgical epididymovasostomy in the rat: comparison of end-to-side and two invagination techniques.

Most cases of obstructive azoospermia are caused by epididymal obstruction for which the classical treatment is epididymovasostomy (EVST). We have compared the widely used end-to-side, invaginated end-to-side and invaginated end-to-end operations. Ninety microsurgical two-layer EVST were carried out on rats. The technical advantages were assessed and patency of anastomoses and conception rate, the length of the operation and amount of suture material used measured in each group. There were no significant differences in patencies and conception rate between the three groups. The invagination techniques took significantly less time than the more usual end-to-side operation, and less suture material was used. The invagination techniques are easier to learn, simpler to perform and involve less manipulation, reduce trauma and cause less laceration to the ductus deferens and epididymal tubules. Economically considered, the operations save the expenditure of both time and suture material. Of paramount importance in making the choice is the size of the ductus deferens and that of the epididymal tubules.

Animals↗
PubMed1999

Semiquantitative analysis of Th1 and Th2 cytokine expression in CD3+, CD4+, and CD8+ renal-cell-carcinoma-infiltrating lymphocytes.

The mRNA expression of Th1 and Th2 cytokines was compared in freshly isolated CD3+ tumor-infiltrating lymphocytes (CD3+ TIL) and in autologous CD3+ peripheral blood lymphocytes (CD3+ PBL) obtained simultaneously from 20 patients with renal cell carcinomas (RCC). In addition cytokine expression was compared in CD4+ TIL and CD8+ TIL from another group of 20 patients with RCC. TIL were isolated from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation and subsequent selection with anti-CD3, anti-CD4 or anti-CD8 magnetic beads. In these pure lymphocyte preparations the constitutive expression of interleukin-1 (IL-1), IL-2, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) was determined by using a polymerase-chain-reaction-assisted mRNA amplification assay. In the CD3+ TIL, levels of mRNA for IFNgamma, IL-10, IL-1 and TNFalpha were significantly higher than in the autologous CD3+ PBL whereas IL-2 expression was rather low and did not differ in the two populations. Comparison of cytokine mRNA expression in CD4+ TIL and simultaneously obtained CD8+ TIL revealed a significantly higher expression of IFNgamma in the CD8+ cells. These data reflect an in vivo activation of RCC-infiltrating lymphocytes at the mRNA level with respect to the Th1 as well as the Th2 immune response. Th1 activation seems to be most evident in the CD8+ TIL.

CD3 Complex↗
PubMed1999

A modified corporoplasty for treating congenital penile curvature and reducing the incidence of palpable indurations.

OBJECTIVE: To reduce the incidence of postoperative palpable induration after treating congenital penile curvature, using a modified corporoplasty technique. PATIENTS AND METHODS: In a retrospective unrandomized clinical trial, 105 patients with a congenital penile angulation of >30 degrees and for whom coitus was therefore difficult or impossible, underwent surgical correction. Of the 105 patients, 55 underwent the Nesbit-Kelâmi technique, whereby a diamond-shaped section of the tunica albuginea is excised and the defect closed with an interrupted suture. The remaining 50 patients underwent the modified corporoplasty, the edges of the tunica albuginea being brought together with a continuous, blood-tight, intratunical suture, and the end knots buried. RESULTS: The early results (<6 months) were comparable in both groups, with correction of the curvature in 94% and 95%, and postoperative complications in 14% and 15%. There were fewer postoperative haematomas in those undergoing modified corporoplasty (6% vs 18%). The late results (>6 months) also showed that these patients developed fewer palpable indurations (16% vs 44%). CONCLUSION: The modified corporoplasty reduced the incidence of postoperative haematoma and late complications (e.g. palpable indurations) after the surgical correction of congenital penile curvature.

Adolescent↗
PubMed1999

Kidney-preserving tumour resection in renal cell carcinoma with photodynamic detection by 5-aminolaevulinic acid: preclinical and preliminary clinical results.

OBJECTIVE: To identify the outer border of a renal cell carcinoma (RCC) during a kidney-preserving tumour resection by photodynamically detecting RCC after the exogenous administration of 5-aminolaevulinic acid (ALA) in an animal model and in humans. PATIENTS, MATERIALS AND METHODS: Human RCC was xenotransplanted subcutaneously and orthotopically into the kidneys of nude mice. ALA was then administered orally or intravenously (100-400 mg/kg body weight). The tumours were removed and examined macroscopically and microscopically for fluorescence, and the concentrations of protoporphyrin IX (PPIX) evaluated in the subcutaneous tumours. In a pilot study, nine patients with RCC of <4 cm diameter underwent partial nephrectomy; 20 mg ALA/kg body weight was given orally 4 h before surgery. During the operation, the macroscopic fluorescence of the tumours was evaluated and any side-effects recorded. RESULTS: In the mouse model, the RCC fluoresced in all tumours, both macro- and microscopically, reaching a maximum 1.5 h after intravenous and 4 h after oral administration. The tissue concentrations of PPIX in the subcutaneous tumours were also maximal 4 h after oral administration. In the patients undergoing surgery, the RCC also fluoresced clearly and was sufficiently intense to identify the outer margins of the tumours for kidney-preserving tumour resection. There were no side-effects of the ALA with the dosages and methods of administration used. CONCLUSION: The photodynamic detection of RCC with ALA facilitates the identification of tumour margins in man and in the mouse model, producing no undesirable side-effects. It may be helpful in determining the boundaries of the resected tissue when carrying out conservative kidney-preserving surgery.

Aminolevulinic Acid↗
PubMed1999

Long-term results of dorsal penile vein ligation for symptomatic treatment of erectile dysfunction.

About 20% of patients with erectile dysfunction do not react to intracavernous pharmacological treatment (SKAT) because of a cavernous leak. The first attempt to treat venous insufficiency goes back as far as the beginning of the century. Ligature and resection of the superficial and deep veins of the penis (DPVL) were performed in 122 patients (nonresponders to SKAT with a maintenance flow of less than 40 ml min-1). Twenty-four patients suffered from primary dysfunction and 98 from secondary dysfunction. The average age of the patients was 49 years, and the average duration of the preoperative erectile dysfunction 4.4 years. Postoperative follow-up was carried out for 70 months. In 98% of the patients, cavernosography revealed a dorsal leak. Twenty-six per cent had ectopic veins, 38% a leakage through the crural veins and 24% a glandular or spongiosal shunt. After the 70-month follow-up, only 14% of the 122 patients were able to achieve an adequate spontaneous erection and 19% also responded to SKAT. Depending upon the time elapsed since the operation, the rate of spontaneous reaction was reduced. It was found that younger patients with a short history of erectile dysfunction, no arterial cofactor, a maintenance flow of less than 100 ml min-1 and a severe dorsal leakage from a DPVL were the most likely to benefit from this procedure. Since degeneration of smooth muscle cells of the cavernosa is in most patients the cause of the venous leakage, penis vein surgery is to be regarded as symptomatic treatment.

Adult↗
PubMed1998

Transurethral resection of cystic and non-cystic ejaculatory duct obstructions.

Ejaculatory duct obstructions are diagnosed in approximately 5% of azoospermic men and can be treated by transurethral resection (TURED) or incision of the ducts. Eight patients with azoospermia and ejaculatory duct obstructions were treated by TURED after clinical examination, semen analysis, biochemical analysis of seminal plasma, endocrine analysis, transrectal ultrasonography and testicular biopsy. In 3/3 cases of cystic and in 3/5 cases of non-cystic obstruction. TURED of the stenosis was possible. During a follow-up of 12 months there was an increase in semen volume and sperm count in 3/3 and 3/5 patients, respectively. No pregnancy was achieved during the period up to 12 months. Clinical symptoms such as haemospermia and pain disappeared in all cases. In our cases and another 98 cases of ejaculatory duct obstructions documented in the literature, men of semen quality improved in 38-60% with a pregnancy rate of men 22-31% after TURED. We conclude that there is a correlation between the aetiology of ejaculatory duct obstructions and success rate of TURED.

Constriction, Pathologic↗