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W Tilgen

Publications and source records attributed to W Tilgen.

At least 91 records · Page 5Linked to original sources
PubMed1995

Interleukin-2-based immunotherapy and chemoimmunotherapy in metastatic melanoma.

This report summarizes our experience in the treatment of advanced melanoma with immunotherapy and chemoimmunotherapy. A total of 45 patients initially received immunotherapy with interferon-alpha (IFN alpha) and a decrescendo regimen of high-dose interleukin-2 (IL-2). The objective response rate is 31% with an additional 36% of mixed response (MR) and stable disease (SD). A total of 18 patients failing immunotherapy with IFN-alpha/IL-2 received subsequent chemotherapy with dacarbacine (DTIC), followed by IFN-alpha. The response rate for this second-line regimen is 22%. A further 11 patients failing IFN-alpha/IL-2 received a single dose of DTIC or cisplatinum (CDDP) on day 1, followed by IFN-alpha/IL-2 according to the same protocol as previously, without chemotherapy. The addition of DTIC or CDDP was fairly well tolerated. Induction of secondary mediators was not inhibited, suggesting that the immunologic effects mediated by IL-2 are not impaired. A randomized clinical trial is now being performed to compare combined chemoimmunotherapy with immunotherapy alone.

Cisplatin↗
PubMed1995

Clinical relevance of sperm morphology assessment using strict criteria and relationship with sperm-mucus interaction in vivo and in vitro.

OBJECTIVE: To determine the relationship of the differentiated morphological pattern of semen samples according to strict criteria and sperm-mucus interaction in vivo and in vitro. PATIENTS: One hundred sixty-three randomly chosen couples with long-standing infertility (median duration of infertility 4 years, range 1 to 19 years). SETTING: Outpatient clinic of the fertility unit at the Women's University Hospital of the University of Heidelberg, Heidelberg, Germany. MAIN OUTCOME MEASURES: Sperm morphology assessment using strict criteria (Tygerberg or Norfolk classification) parallel to standard methods of sperm analysis: Evaluation of the cervical factor of patients' female partners, including a microbial screening of genital secretions of both partners; Examination of sperm migration ability in vivo under hormonally controlled conditions for the cervical mucus (CM) quality and in vitro with the crossed sperm-CM penetration test performed with CM of patients' partners, as well as with CM and spermatozoa of donors; Determination of the selection capacity of CM with regard to sperm morphology by means of a biological model; Prospective analysis of the differentiated morphological pattern with respect to couples' subsequent fertility within 6 months. RESULTS: Using stict criteria, amorphous sperm heads were the most frequently found sperm anomaly (severely amorphous forms: median, 28%; range, 4% to 62%). The morphology index offered a median of 45% (range, 7% to 80%). Results correlated significantly with routine sperm analysis, including standard morphology. The morphological pattern differed significantly in samples offering adequate or inadequate ability to penetrate CM in the standardized sperm-CM penetration test or in the postcoital test, with the percent of severely amorphous heads as the most important parameter. Neck and tail defects did not play an important role. During passage of mucus columns in vitro, the rate of pathological spermatozoal forms was reduced significantly, from a median of 65% to a median of 38%. Better functional capacity of spermatozoa with normal head morphology also was reflected by a significantly higher pregnancy rate under natural conditions of conception. CONCLUSIONS: Sperm morphological properties, determined with strict criteria, are important factors for sperm ability to penetrate the mucus barrier at the uterine cervix before reaching the site of fertilization, but sperm morphology is only one among other parameters determining the complex phenomenon of sperm-mucus interaction.

Adult↗
PubMed1995

Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and treatment effectiveness. A multicentre phase II trial of the EORTC-Melanoma Cooperative Group (MCG).

Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2 on days 1 + 8 + 15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligible vs non-eligible patient group (in parentheses) were as follows: male/female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0-1 (0-4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4-16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III+IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Adjuvant and palliative therapy of melanoma. Current status].

Even though there are a couple of therapeutic concepts for the metastatic malignant melanoma and new protocols are being designed there is no cure for this tumor in the advanced stage. By carefully analyzing the results surgical therapy, radiation and chemotherapy can be named as the standard therapies. But different protocols of combined chemo- and immunotherapy, adjuvant therapies e.g. with tumor vaccines are being tried out. Experimental approaches are photodynamic therapy, the application of monoclonal antibodies and gene therapy.

Chemotherapy, Adjuvant↗
PubMed1994

Dose comparison of tropisetron (Navoban) 5 mg and 10 mg orally in the prophylaxis of dacarbazine-induced nausea and emesis.

In this double-blind, randomized trial performed at five study centers, the prophylactic, antiemetic effect of two different dosages of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) was investigated in dacarbazine-treated patients with melanoma. Patients received tropisetron 5 mg or 10 mg orally (as one capsule) once daily (minimum 3 days) on each day of chemotherapy. No significant differences were found in the effects of tropisetron 5 mg and 10 mg. During the first 24 hours, total control of vomiting was seen in 93% and 98% of patients receiving tropisetron 5 mg and 10 mg, respectively. Total control of nausea was achieved in 84% and 80% of patients receiving tropisetron at these dosages. Over days 2 to 7 of chemotherapy, total control of vomiting and nausea remained high. Patients reported that quality of life remained good throughout chemotherapy, as did mood; only a small decrease in food intake occurred. Tropisetron was well tolerated. Constipation was the most common adverse event, occurring in 13% of patients. Headache (4%), diarrhea (4%), and anorexia (2%) also were observed.

Administration, Oral↗
PubMed1993

Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma. Comparison of two phase II trials.

BACKGROUND: Interferon-alpha (IFN alpha) and interleukin-2 (IL-2) are active agents against malignant melanoma. There is, however, no consensus on the optimal dosing schedule of both drugs. This is a report of two sequential immunotherapy trials in patients with metastatic melanoma using two different IL-2 dosing schedules. METHODS: Schedule A consists of IFN alpha, 10 million U/m2/day subcutaneously for 5 days, followed by continuous intravenous infusion of IL-2, 1 mg/m2/24 hours for 5 days. Schedule B consists of the same dose of IFN alpha, but a modified regimen of IL-2. To improve the induction of high-affinity IL-2 receptors, the initial IL-2 dose was increased (1 mg/m2/6 hours, followed by 1 mg/m2/12 hours, and 1 mg/m2/24 hours). To reduce toxicity, the dose was reduced thereafter to 0.25 mg/m2/24 hours for the following 3 days. Both regimens were repeated after 4 weeks. RESULTS: 27 patients were treated with schedule A with a response rate of 18% (1 complete response [CR], 4 partial responses [PR]), 95% confidence interval, 6-36%. The response rate in 27 patients treated with schedule B was 41% (3 CR, 8 PR), 95% confidence interval, 22-61%. Severe, often dose-limiting toxicity was associated with IL-2 in schedule A, particularly hypotension and fluid retention. Toxicity was reduced significantly in schedule B. Maximal serum levels of soluble CD25 were 17,022 +/- 13,070 U/ml in schedule A, and 31,148 +/- 4227 U/ml in schedule B (P < or = 0.01). Serum levels of TNF alpha were significantly lower in schedule B than in schedule A, as were the side effects. CONCLUSIONS: Toxicity of IL-2 is reduced by modifying the schedule of administration, which also enhances the immunologic response and appears to increase the response rate.

Adult↗
PubMed1993

Differential expression and release of LFA-3 and ICAM-1 in human melanoma cell lines.

We examined 10 different melanoma cell lines for cellular expression and release of ICAM-1 (CD54) and LFA-3 (CD58) and the influence of cytokines, including IFN alpha, IFN gamma and TNF alpha. Cellular ICAM-1 expression and density varies considerably between the melanoma cell lines. While IFN alpha has no effect on cellular ICAM-1 (cICAM-1) expression, IFN gamma and to a lesser extent TNF alpha can effectively up-regulate cICAM-1. Soluble ICAM-1 (sICAM-1) is detected in the supernatants of all lines tested, release of sICAM-1 correlates with cellular expression. LFA-3 does not much differ in its expression level on melanoma lines, and cytokines have little or no effect on its expression. Soluble LFA-3 is released by only 6 out of 10 lines. Its release can effectively be inhibited by IFN gamma in all lines and by TNF alpha in one, while IFN alpha has no effect. These data show that expression and release of LFA-3 and ICAM-1 differ between melanoma cell lines. This may be of importance for the interaction of melanoma cells with immune effector cells in vivo.

Animals↗
PubMed1993

Granuloma annulare perforans in herpes zoster scars.

Granuloma annulare perforans limited to a thoracic dermatome that was previously involved by herpes zoster occurred in a 51-year-old woman who also had Lennert's lymphoma. Of the various local granulomatous infiltrates described after herpes zoster, granuloma annulare perforans is unique, although ordinary granuloma annulare has been described in a few patients. A high incidence of specific and nonspecific reaction patterns in herpes zoster scars has been described in patients with malignant lymphoma. In contrast to previous patients, all of whom had chronic lymphatic leukemia, our patient had Lennert's lymphoma.

Back↗
PubMed1993

Evaluation of polyacrylamide gel as substitute for human cervical mucus in the sperm penetration test.

OBJECTIVE: To compare polyacrylamide gel as synthetic medium with human cervical mucus (CM) for the in vitro sperm-penetration test during infertility investigation. PATIENTS: One hundred sixty-nine randomly chosen couples with a median duration of infertility of 4 (range, 1 to 16) years presenting at the infertility unit of the Women's University Hospital of Heidelberg, Germany. MAIN OUTCOME MEASURES: Evaluation of sperm migration in polyacrylamide gel used in four different concentrations (1.5%, 1.6%, 1.7%, 1.8%) in the capillary tube test in parallel with CM of patients' female partners and CM of fertile donors, obtained under standardized conditions. Correlation of migration test results with outcome of semen analysis including microbial cultures and testing for local antisperm antibodies by means of the mixed antiglobulin reaction, postcoital testing, and the subsequent pregnancy rate after control for female infertility factors in a prospective study. RESULTS: Sperm ability to penetrate the synthetic medium (concerning all concentrations) correlated significantly with the penetration of human CM, although polyacrylamide proved to be a stronger barrier. Sperm velocity and duration of progressive motility were markedly reduced in polyacrylamide. Polyacrylamide results correlated with the outcome of standard sperm analyses but not with sperm antibody testing. No clear differentiation was obtained with regard to subsequent fertility (19% after 6 months), although adequate sperm migration in polyacrylamide 1.8% was significantly more frequent in the fertile group. CONCLUSIONS: In analyzing the intrinsic motility, penetration testing with polyacrylamide gel provides important information not obtained by routine sperm analysis. However, particularly with regard to immunological factors and fertility prognosis, human CM should be preferred whenever possible.

Acrylic Resins↗
PubMed1993

Antisperm antibodies in cervical mucus in an unselected subfertile population.

To determine the incidence and the clinical significance of antisperm antibodies (ASA) in cervical secretions in an unselected subfertile population, cervical mucus samples of 192 patients with long-standing infertility were screened by means of the indirect mixed antiglobulin reaction (MAR) test allowing differentiation for immunoglobulin (Ig)A and IgG in a parallel test setting. In addition, the indirect MAR IgG test in cervical mucus was evaluated by means of IgG coated latex particles instead of sensitized erythrocytes as the indicator system. All cervical mucus samples were taken under standardized conditions. Results of ASA determination were related to microbial findings in the cervix and the outcome of sperm-mucus interaction testing in vivo and in vitro, and the subsequent fertility in a prospective study. The total incidence of cervical mucus ASA within this population was low (< 2%). A significant correlation was found between sperm antibodies of the IgG and IgA class and of IgG ASA, determined with the standard MAR and testing with latex microspheres as indicator particles. Results were not influenced by microbial colonization of the cervix and were not markedly related to lymphocytes subset testing. All ASA positive women had a negative outcome of the post-coital test, but the majority of negative post-coital tests was not caused by local mucus antibodies of the IgG and/or IgA class. In patients with positive indirect MAR testing in cervical mucus, there was no pregnancy within an observation period of > 12 months. In conclusion, the results indicate the ASA in cervical secretions are not frequent but nevertheless are a severe cause of infertility when present.(ABSTRACT TRUNCATED AT 250 WORDS)

Cervix Mucus↗
PubMed1992

Regional administration of lymphokine-activated killer cells can be superior to intravenous application.

A patient with liver metastases of human lymphocyte antigen (HLA) class II-negative malignant melanoma was treated with several cycles of adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells. The authors evaluated the efficacy of regional transfer of LAK cells versus systemic intravenous administration. Initially, the patient was treated according to a regional treatment protocol, consisting of perfusion of the spleen with interleukin-2 and transfer of LAK cells into the portal vein; a partial remission was observed. Because of technical problems, interleukin-2 and LAK cells were administered intravenously in a second treatment cycle. This systemic treatment course resulted only in a minor mixed response of the hepatic metastases. A third treatment course was administered with the use of intravenous interleukin-2 infusion and arterial perfusion of the liver with LAK cells. The patient had separate hepatic arteries to both lobes of the liver as an anatomic variation. Because most of the tumor mass was present in the right lobe of the liver, a third of the LAK cells were injected into the right hepatic artery and the remaining cells were administered intravenously. The lesions in the right lobe of the liver regressed, but disease progression occurred in the left lobe. A fourth treatment cycle, consisting of intravenous infusion of interleukin-2 and arterial perfusion of both lobes of the liver with LAK cells, resulted in a complete response of all hepatic lesions, which has lasted 18 months to date. Because, in this patient, tumor regression was observed only in anatomic areas of the liver, which were perfused with LAK cells, it is suggested that the regional administration of LAK cells was essential for successful treatment.

Adult↗
PubMed1992

Differentiation of round cells in semen by means of monoclonal antibodies and relationship with male fertility.

OBJECTIVE: To differentiate round cells in semen samples of subfertile men and evaluate the clinical significance during infertility investigation. PATIENTS: One hundred and eight randomly chosen couples with a median duration of infertility of 4 (range, 1 to 20) years presenting at the outpatient infertility clinic of the University of Heidelberg, Germany. MAIN OUTCOME MEASURES: Differentiation of round cells in semen by means of monoclonal antibodies (mABs) and a streptavidin-biotin system for staining. Correlation of results with medical history, outcome of clinical examination, sperm analysis, microbial screening of both partners, evaluation of sperm functional capacity in vivo by means of the postcoital test (PCT) and in vitro with the standardized crossed sperm-cervical mucus penetration test (SCMPT) and the subsequent fertility in a prospective study. RESULTS: The method used for differentiation of round cells proved to be practical and suitable for routine use. The percentage of leukocytes ranged from 0% to 58% with a median of 3%. Number of round cells and percentage of leukocytes did not differ markedly with regard to andrologic history, clinical findings, for example, varicocele, results of standard sperm analysis, and microbial colonization of semen samples. However, high rates of leukocytes of the round cells correlated with reduced sperm count and morphology and results of PCT. Leukocyte-positive (> 15% leukocytes) specimens were also significantly more frequent in case of inadequate SCMPT and reduced sperm penetration ability in vitro. CONCLUSIONS: In asymptomatic patients (in terms of genital tract infection), the majority of round cells consist of immature germ cells and < 5% are white blood cells. The streptavidin-biotin system and the mABs used in this study proved to be useful to identify patients with elevated rates of leukocytes in semen possibly reflecting subclinical genital tract infection with influence on sperm functional capacity and subsequent fertility. Thus the procedure can be recommended to be included in a comprehensive evaluation of male fertility.

Adult↗
PubMed1992

Microbial colonization and sperm--mucus interaction: results in 1000 infertile couples.

After screening a large series of infertile patients (n = 1000 couples), potentially pathogenic microorganisms were identified in genital secretions of the majority of couples. None of the patients displayed signs or symptoms of infection of the lower genital tract. In semen specimens and cervical swabs, mycoplasmas were found in 18 and 12%, potentially pathogenic aerobic bacteria in 50 and 31%, additionally commensal aerobes in 38% and 25%, respectively. The microbial pattern showed great variability with polymicrobial growth most common. The rate of cultures positive for potentially pathogenic anaerobes was markedly influenced by the transport conditions. In endocervical material, Herpes simplex virus (HSV) was identified in 4.5%. Yeasts were found in the posterior vaginal fornix in 10%. Concerning both partners, there were only 10 couples (1%) from whom microorganisms in genital secretions could not be isolated, not including lactobacilli in females. This high prevalence of microbes and the low number of leukocytes indicate colonization rather than infection. When the microbial findings from both partners were analysed with regard to the outcome of sperm-cervical mucus penetration testing in vitro, which was performed simultaneously, no significant correlation was found. Furthermore, microbial prevalence did not differ between couples with 'explained' and 'unexplained' infertility. The results of this study demonstrate that in patients without symptoms of genital tract infection, microbial colonization is of minor importance for sperm--mucus interaction and that extensive microbial screening should be preferentially performed in cases of poor sperm and/or mucus function.

Adult↗
PubMed1992

Alpha 2-macroglobulin and alpha 2-macroglobulin/proteinase complexes in human seminal fluid.

OBJECTIVE: To determine the broad-spectrum proteinase inhibitor alpha 2-macroglobulin (alpha 2M) and its functional subforms, i.e., free alpha 2M and alpha 2M/proteinase complexes, in human seminal fluid by using specific enzyme immunoassay systems. SETTING: The study has been performed in the Andrology Department of the Dermatology Clinics and the Laboratory of Immunopathology of the Institute of Immunology. PATIENTS, PARTICIPATES: Routine patients attending the Andrology Department. INTERVENTIONS: The data have been obtained without particular interventions before or after collection of seminal fluid. MAIN OUTCOME MEASURES: The aim of the study was to determine whether alpha 2M or alpha 2M/proteinase complexes are present in human seminal fluid. RESULTS: The concentration of total alpha 2M in human seminal fluid ranged from 1 to greater than 1,000 ng/mL, and between 56% and 85% of the inhibitor was complexed with proteinases. CONCLUSIONS: These findings show that alpha 2M and alpha 2M/proteinase complexes have to be considered as functionally relevant biomolecules in male genital tract secretions.

Endopeptidases↗
PubMed1991

Relationship between local anti-sperm antibodies and sperm-mucus interaction in vitro and in vivo.

Sperm-mucus interaction under in-vitro or in-vivo conditions can be affected by local anti-sperm antibodies (ASA). In a prospective study, a mixed antiglobulin reaction (MAR) test, using immunoglobulin-coated red cells and spermatozoa, was used to detect the presence of IgG and/or IgA on the spermatozoal surface in 209 males of infertile partnerships. The results of direct MAR tests range from 0 to 100% and a significant correlation between MAR % IgG and MAR % IgA (r = 0.74) was found. MAR positive semen samples were significantly more frequent in the group of patients with an inadequate outcome of postcoital testing (PCT). The sperm-mucus interaction in vitro, evaluated by means of the in-vitro sperm-cervical mucus penetration test (SCMPT) with cervical mucus (CM) of patients' partners, was particularly related to spermatozoal surface antibodies of the IgA class: MAR IgA positive ejaculates were seen in 13.9% of males with inadequate SCMPT versus 4.4% when SCMPT was adequate. The significant correlation between MAR IgA and the sperm penetration ability in vitro could also be proven when donors' CM was taken for the SCMPT, but not when a non-human material was used for in-vitro penetration testing. Microbial colonization of semen specimens did not interfere with the outcome of MAR testing. The pregnancy rate after 12 months was 23% (48/209) and was significantly lower when greater than 30% of spermatozoa were covered with surface ASA of the IgG or IgA class.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗