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Biomedical subjects

W Wilmanns

Publications and source records attributed to W Wilmanns.

At least 73 records · Page 4Linked to original sources
PubMed1994

Sequential resection of residual abdominal and thoracic masses after chemotherapy for metastatic non-seminomatous germ cell tumours.

Thirty-eight patients with advanced non-seminomatous germ cell tumours (NSGCTs) underwent multiple surgical interventions (two in 33 patients, three in four patients, four in one patient) after cisplatin-based chemotherapy. All patients had normal serum tumour markers but persistent radiographic masses. The larger mass was routinely resected first. Fifteen patients (39%) had dissimilar histological findings at sequential surgical procedures, 12 of whom demonstrated less favourable pathological features during the first operation and three at the second. Patients who underwent both retroperitoneal lymph node dissection (RPLND) and lung resection showed less favourable histological features in the retroperitoneum in nine cases and in the lung in three cases. Eight of 16 patients (50%) without mature teratoma in their primary tumours showed complete necrosis/fibrosis at all surgical interventions, whereas all patients whose primary tumour was classified as malignant teratoma intermediate demonstrated mature teratoma at least at one anatomical site. As histology of post-chemotherapy residual masses cannot be extrapolated from one anatomical site to another, patients usually are properly managed by excision of all residual masses. In particular, in patients with necrosis/fibrosis at lung resection omission of RPLND is not advised.

Abdominal Neoplasms↗
PubMed1994

Granulocyte colony-stimulating factor inhibits the endogenous leukotriene production in tumour patients.

Granulocyte colony-stimulating factor (G-CSF) is virtually devoid of inflammatory side-effects when given to patients in therapeutic doses. This is in contrast to other haemopoietic cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) which may promote inflammatory reactions by increasing the number and/or activity of monocytes, eosinophils, mast cells and basophils. Inflammatory reactions to GM-CSF and IL-3 appear to be related to an increased formation of leukotrienes, known as potent mediators of allergy and inflammation. Here we report that, in contrast to GM-CSF or IL-3, G-CSF has the potential to inhibit the leukotriene production in vivo. G-CSF may thus act as an anti-inflammatory agent. The differential effects of G-CSF and other haemopoietins on endogenous leukotrienes may be of major clinical significance.

Granulocyte Colony-Stimulating Factor↗
PubMed1994

Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation.

Prevention of graft-versus-host disease by depletion of CD6-positive T cells was studied in the dog. Donors were DLA-homozygous, recipients DLA-heterozygous with one DLA haplotype identical to the donor. Seven control dogs received untreated marrow and died of GvHD after full hemopoietic recovery within 28 days of transplantation. For prevention of GvHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells completely, but only part of CD8-positive cells and DR-positive cells. CD6-depleted marrow exhibited strong nonspecific "natural" suppression of the generation of cytotoxic T cells in vitro. Eleven dogs received CD6-depleted marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8 dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6-depleted marrow than after transplantation of untreated marrow. Four of these dogs were treated with G-CSF, and this accelerated the recovery of leukocytes, but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prevents GvHD across a DLA-haplotype difference, but rejection and mixed chimerism may occur. Treatment with G-CSF accelerates leukocyte recovery, but cannot prevent rejection.

Animals↗
PubMed1994

Testicular tumor after cisplatin-based chemotherapy for germ cell malignancy.

Among 417 patients treated with cisplatin-based chemotherapy for germ cell malignancy (median follow-up 7 years) we observed 6 patients who developed a second tumor of the testis. In 3 cases the first tumor was of testicular origin, whereas in the other cases the initial tumor presented in the retroperitoneal space. Although cisplatin-based chemotherapy may reduce or delay the development of a contralateral testicular tumor, the risk apparently is not completely eliminated. Patients with primary retroperitoneal germ cell tumors need a close and careful follow-up, as they appear to be at an increased risk for developing a testicular tumor.

Adult↗
PubMed1994

Parameters of the fibrinolytic system in patients undergoing BMT: elevation of PAI-1 in veno-occlusive disease.

Veno-occlusive disease (VOD) represents one of the more frequent and most severe complications after BMT. The pathophysiology of VOD is poorly understood. To investigate a possible link between endothelial cell damage and VOD, tissue plasminogen activator (tPA) and its inhibitor (PAI-1) were measured in 32 patients as endothelial cell-derived parameters of the fibrinolytic system. A nearly fivefold increase (mean 103.9 ng/ml, range 22.6-582.4 ng/ml, p < 0.05) in PAI-1 levels was found in the four patients who developed VOD compared with patients without this complication (mean 22.2 ng/ml, range 1.4-131.6 ng/ml). No significant difference was found in tPA levels between patient groups with or without VOD or other complications following BMT, indicating a shift of the fibrinolytic balance towards hypofibrinolysis particularly in patients with VOD. We conclude that alterations of the fibrinolytic system occur in patients undergoing BMT. Hypofibrinolysis seems to be at least one factor in the pathogenesis of VOD and the determination of PAI-1 might be helpful for diagnosing the disease. Our data also may explain the reported successful treatment of VOD by recombinant tPA.

Bone Marrow Transplantation↗
PubMed1993

Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas.

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.

Adolescent↗
PubMed1993

Testicular cancer and Hodgkin disease in the same patient.

BACKGROUND: Although testicular cancer and Hodgkin disease are the neoplasms with the highest incidence in young men, only 13 cases of metachronous and 2 cases of synchronous occurrence in the same person were reported before 1991. METHODS: A 30-year-old man is described, in whom, 2 years after radiation therapy for Stage IIIA Hodgkin disease, a testicular nonseminomatous germ cell tumor developed with metastatic spread to the retroperitoneal lymph nodes, lung, and left supraclavicular fossa. The second case report describes a 31-year-old man in whom a metastasizing nonseminomatous testicular cancer, with elevation of levels of the serum tumor markers alpha-fetoprotein and human chorionic gonadotropin, developed simultaneously with axillary lymphadenopathy that was histologically confirmed Hodgkin disease. RESULTS: After five cycles of cisplatin-based chemotherapy and secondary retroperitoneal lymphadenectomy, the patient with metachronous disease has remained in complete remission for 8 years. The patient with synchronous occurrence has been disease-free for 14 months after five cycles of chemotherapy consisting of cisplatin, etoposide, and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH). CONCLUSIONS: The metachronous and synchronous occurrence of testicular cancer and Hodgkin disease is a rare association of two curable neoplasms. The presence of both malignant neoplasms should be taken into consideration in young male patients, especially if disease distribution diverges from a regular pattern.

Adult↗
PubMed1993

Differential activation of the endogenous leukotriene biosynthesis by two different preparations of granulocyte-macrophage colony-stimulating factor in healthy volunteers.

Results from in vitro investigations and recent data obtained in patients with drug-induced cytopenia or myelodysplasia suggest that leukotrienes may be involved in mediating some of the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, the possible role of leukotrienes was further characterized in 21 healthy individuals to avoid modification of response to GM-CSF by disease-specific variables. The effects of two different preparations of human recombinant GM-CSF, ie, glycosylated GM-CSF as expressed in a Chinese hamster ovary carcinoma (CHO) cell line and nonglycosylated GM-CSF obtained from Escherichia coli, were compared. GM-CSF was administered subcutaneously at a single dose of 0.7 nmol/kg body weight. Pharmacokinetic parameters and hematopoietic and adverse effects were monitored by blood analyses or physical examination, respectively. Leukotriene generation in vivo was evaluated by determination of leukotriene E4 and N-acetyl-leukotriene E4 in urine. After the injection of GM-CSF from E coli, serum concentrations increased and decreased more rapidly and reached a 2.3-fold higher maximum compared with GM-CSF from CHO. GM-CSF induced a biphasic change in leukocyte counts that proceeded considerably faster after the E coli preparation than after GM-CSF from CHO. The urinary leukotriene concentration increased 1.3- to 14-fold or 2.1- to 44-fold after the administration of GM-CSF from CHO or E coli, respectively. Urinary leukotriene concentrations correlated significantly with the maximum of basophil counts and correlated with the occurrence of some adverse reactions, ie, flu-like symptoms, bone pain, or dyspnoea. Our data confirm the conception that leukotrienes may play a significant role in GM-CSF action in vivo. They especially direct attention to the possible relevance of leukotrienes to untoward effects of GM-CSF treatment.

Adult↗
PubMed1993

Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs.

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe rendered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were HinfI and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after HinfI digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation.

Adult↗
PubMed1993

IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study.

Modern combination chemotherapy cures about one third of patients with non-Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study.

Adult↗
PubMed1993

Ifosfamide induced stress response in human lymphocytes.

Ifosfamide, an isomer of cyclophosphamide, has been shown to be one of the most effective antineoplastic agents for the treatment of human malignancies. There is considerable evidence that the intracellular status of glutathione (GSH) plays a major role in modifying the cytotoxicity of ifosfamide in cells and tissues. We have studied the effects of 4-hydroperoxy-ifosfamide (4-OOH-IF) upon the proliferation of human peripheral blood lymphocytes (PBL) and the intracellular GSH content. The major finding was that occurrence of significant inhibition of [3H]-thymidine incorporation in interleukin-2 (IL-2) expanded PBL after exposure with 4-OOH-IF was accompanied by substantial depletion of intracellular GSH content in these cells. PBL seemed to be more sensitive to this drug induced effect comparing our results obtained in other cells (e.g. Ewing sarcoma, Chinese hamster ovary). In PBL 4-OOH-IF also induced rapid phosphorylation of the small heat shock protein (HSP27) signaling a similar type of stress response as reported for several other agents (e.g. arsenite, phorbol ester, tumor necrosis factor). Reconstitution of the depleted GSH content in PBL after treatment with 4-OOH-IF could be achieved by GSH-monoethylester and mesna within 24 hours of postincubation time. From these results we conclude that human lymphocytes are sensitive targets for ifosfamide induced metabolic stress during treatment. This might have further importance in regard to the immunological function of these cells.

Blotting, Western↗
PubMed1993

Intervention treatment of established neutropenia with human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients undergoing cancer chemotherapy.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to 60 patients, in a double-blind, non-prophylactic study of already established chemotherapy-induced leucopenia, for 5 days by continuous intravenous infusion and twice or once daily by subcutaneous injection. Four patients were randomized to rhGM-CSF (3) or placebo (1) at each dose (1.3, 1.7, 5.5, 11, or 22 micrograms of protein/kg). Leucocyte recovery was significantly enhanced compared with controls, in a dose-dependent manner except for 22 micrograms/kg which was ineffective with a worse experience of side effects in some patients. Most adverse events occurred in equal proportions in the treated and placebo cases. Fourteen patients developed infection and were treated with antibiotics in addition to rhGM-CSF. They were joined by a further 18 febrile patients and treated with rhGM-CSF in a subsequent open-label trial. The survival from infection was related to white blood cell (WBC) count: 19 of 32 responded with increased numbers of leucocytes (WBC count above 1.5 x 10(9)/1) after 5 days of GM-CSF. Sixteen of the 19 leucocyte 'responders' recovered from infection, two died from the underlying disease and one from persistent infection. Six of the 13 patients who did not have a leucocyte response died with persistent infection. These data indicate that rhGM-CSF enhances the leucocyte count following chemotherapy and in this way saves critically ill neutropenic patients from fatal infections.

Adult↗