PubMed Health⌕ Search

Biomedical subjects

M Schietzel

Publications and source records attributed to M Schietzel.

At least 19 recordsLinked to original sources
PubMed2003

[Retrospective study of malignant melanoma patients treated with mistletoe extracts].

OBJECTIVE: The aim of the present investigation was to analyze survival time and survival rate of all patients with malignant melanoma who had been counseled at the Tumorambulanz Herdecke of the Community Hospital Herdecke. PATIENTS AND METHODS: 284 melanoma patients were included in a retrospective questionnaire study. Only those patients were considered for analysis in whom the prognostic factors histology, tumor localization, and Clark level were known. The data of the study population were compared with patient data obtained from the literature. RESULTS: 94 patients were included in the analysis. 66 of whom had received and 7 had not received mistletoe treatment, in the remaining 21 patients there was no information whether or not mistletoe treatment had been given. Thus, we did our study without a clearly defined internal control group. The median survival time among patients treated with mistletoe had been 14.1 years. The 5- and 10-year survival rates were 80 and 68% for the mistletoe-treated patients, respectively. DISCUSSION: The 5-year survival rate of the mistletoe-treated patients is comparable to that of patients without mistletoe therapy while the 10-year survival rate is a little bit lower. This may be due to the fact that, in contrast to the patients from the relevant literature, 33.3% of the patients suffered from lymph node and/or distant metastases already before counseling the Tumorambulanz Herdecke. Moreover, 50% of our patients had melanoma of Clark level IV in contrast to 22.2% or 31% in the relevant literature. CONCLUSIONS: In spite of the theoretical reservations against mistletoe treatment in melanoma patients, our retrospective analysis did not show any clues about disadvantages of mistletoe treatment in melanoma patients. A controlled prospective study therefore should prove the efficacy of a mistletoe therapy in patients with malignant melanoma.

Female↗
PubMed2001

[Breast cancer recurrence versus scar. Ultrasonographic differentiation using Levovist as the contrast medium].

AIM: To determine the scope of improving the distinction between a postoperative scar and the recurrence of a breast carcinoma through the use of the ultrasound echo enhancer Levovist? METHOD: In 23 patients with 26 lesions a colour-coded duplex sonography examination before and after administration of Levovist was performed. The parameters investigated were: degree of enhancement, number of tumour vessels and the pattern of vascular morphology and anatomy. RESULTS: Recurrences (n = 15) demonstrated a greater number of vessels and a stronger enhancement after administration of Levovist. Individual vessels were also visible in scars (n = 11). Further evaluations with respect to the pattern of the tumour vascularization are therefore necessary with the exception of one false positive and one negative result a clear distinction was possible. CONCLUSION: The administration of the ultrasound echo enhancer clearly improved the otherwise difficult distinction between a scar and a tumour recurrence through sonography and mammography. Further studies with larger number of patients are necessary to establish the value of the method.

Adult↗
PubMed2000

Expression of interleukin-4 in apoptotic cells: stimulation of the type-2 cytokine by different toxins in human peripheral blood mononuclear and tumor cells.

BACKGROUND: Immunological reactivity is regulated by T-cell populations (type-1 and type-2 cells) via cytokine secretion, but their influence on apoptosis remains unclear. METHODS: Intracellular expression of type-1 (interferon [IFN]-gamma) and type-2 (interleukin [IL]-4) cytokines and apoptosis-related molecules (Apo2. 7, Bcl-2 protein) was studied by flow cytometry in human peripheral blood mononuclear cells (PBMC), myeloma (U-266), monocytic (THP-1), and T-leukemia cells (MOLT-4) in response to toxins, which act on different intracellular targets (actinomycin D, cycloheximide, the mistletoe lectins [ML]-1 and ML-3, brefeldin A, staurosporine). RESULTS: The apoptosis-inducing toxins stimulated intracellular IL-4 expression mainly in PBMC with high expression of the mitochondrial apoptosis marker, Apo2.7, but with decreased level of the anti-apoptotic Bcl-2 protein. Up-regulation of IL-4 coincided with a significant down-regulation of IFN-gamma in CD4(+) and CD8(+) cells. The inhibitor of oxidative phosphorylation, oligomycin, and the caspase inhibitor, z-VAD-fmk, abolished IL-4 expression and DNA fragmentation in the PBMC. Also in the myeloma, monocytic, and T-leukemia cells, IL-4 was mainly observed in the Apo2.7(+) apoptotic cells in response to the toxins. CONCLUSIONS: We suggest that the different apoptotic toxins activate a common pathway in which IL-4 production plays a yet unknown intracellular role further downstream during apoptosis.

Apoptosis↗
PubMed2000

[Mistletoe extracts in the therapy of malignant, hematological and lymphatic diseases--a monocentric, retrospective analysis over 16 years].

OBJECTIVE: The aim of the present investigation was to investigate potentials risks of treatment with mistletoe extracts in patients with malignant haematological and lymphatic diseases consulting the Tumour Ambulance of the Community Hospital Herdecke and to evaluate the therapeutic experiences with this treatment. PATIENTS AND METHODS: All 700 patients with these diseases who had been counselled at the Tumour Ambulance of Community Hospital Herdecke since the foundation of the unit were included in a retrospective questionnaire study to collect information on the course of the disease and the survival time. Therapy with mistletoe extracts had been recommended to all patients. The treatment was carried out by the patient's physician outside the hospital. For inclusion into further analysis, information on survival time and mistletoe treatment had to be available. Survival times of patients who had actually received the recommended mistletoe treatment and of patients who had not received the recommended mistletoe treatment were compared (internal comparison). Furthermore, the results were compared to those of conventionally treated patients obtained from the literature (literature comparison). RESULTS: Of 237 patients for whom sufficient data was available, 14 had not been treated with a mistletoe extract. The median survival time was 9.18 years among patients who had received mistletoe compared to 7.54 years among those without. Before a statistical test was carried out, the equivalent distribution of diagnosis in the 2 groups was tested. Regarding this criterion, only 205 patients treated with mistletoe extract and 9 patients not treated with mistletoe extract could be included into the statistical tests of the median survival time. The median survival time was 11.4 years (mistletoe patients) and 8.6 years (patients without mistletoe therapy). The difference was not significant. There were no cases in which mistletoe treatment was associated with deterioration. The comparison with data from the literature yielded very similar survival times among patients not treated with mistletoe extract and those included in our study. CONCLUSION: No indications to risks of a mistletoe therapy on progress of the disease and the survival time could be found. Therefore, no ethical reservations should be opposed to future prospective investigations of mistletoe therapy in patients with malignant haematological diseases.

Female↗
PubMed2000

Tumor vascularity of breast lesions: potentials and limits of contrast-enhanced Doppler sonography.

OBJECTIVE: We investigated improving the evaluation of benignity in breast lesions using Doppler sonography with galactose palmitic acid-coated microbubbles. SUBJECTS AND METHODS: In 77 patients with 84 breast tumors scheduled for surgical tumor removal, color-coded duplex sonography was performed before and after administration of Levovist. Of the 77 patients, 25 with 28 lesions had been treated for prior breast carcinoma. The parameters investigated were the following: degree of enhancement, number of tumor vessels, time to maximum enhancement, and the pattern of vascular morphology and course. RESULTS: Findings in malignant tumors (n = 53) showed a greater number of vessels and a faster stronger enhancement after Levovist administration, whereas a definite partial overlap with results from benign tumors (n = 31) was found. The best distinction was produced by vascular morphology and course, with a sensitivity of 90% and a specificity of 81 %. In 23 of the 25 patients who previously underwent surgery, a clear distinction was possible between a postoperative scar (n = 11) and a tumor recurrence (n = 17). CONCLUSION: Although administration of the contrast agent clearly improved evaluation of benign features on Doppler sonography, absolute certainty cannot be achieved. The feasibility of making an otherwise difficult distinction between a scar and tumor recurrence on sonography and mammography appears to be promising, but further studies are necessary.

Breast Neoplasms↗
PubMed1999

Expression of mitochondrial Apo2.7 molecules and caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins.

BACKGROUND: It is unclear whether expression of newly described mitochondrial Apo2.7 molecules (7A6 antigen) is specific for apoptosis or may also occur in necrosis. METHODS: We incubated human lymphocytes with the apoptosis-inducing mistletoe lectin (ML) I and the cell membrane-permeabilizing viscotoxins (VT), and measured cell death-associated changes by flow cytometry. RESULTS: In ML I-treated lymphocytes, Apo2.7 expression and caspase-3 activation was recognized within 24 h. In VT-treated cells, we observed an Apo2.7 expression with low fluorescence level, while active caspase-3 and DNA fragments (TUNEL) were not detected within 24 h. In these cells, caspase-3 activation was recognized 48 h later. As a major subset of ML-treated cells expressing Apo2.7 molecules did not activated caspase-3, while all caspase-3(+) cells did express Apo2.7, one may suggest that the caspase pathway is activated secondarily to mitochondrial events. CONCLUSIONS: Expression of Apo2.7 is sensitive marker of cell death but may not be specific for apoptosis alone as it can be detected also in cells treated with cell membrane-permeabilizing toxins. On the other hand, this expression may be the consequence of an induction of distinct "death signals" resulting in apoptosis later on.

Apoptosis↗
PubMed1999

Induction of mitochondrial Apo2.7 molecules and generation of reactive oxygen-intermediates in cultured lymphocytes by the toxic proteins from Viscum album L.

We analysed mitochondrial alterations in human lymphocytes incubated with toxins exerting RNA and/or protein synthesis/transport inhibitory activity. We found that all toxins known to affect macromolecule synthesis, such as ricin from Ricinus communis, mistletoe lectin I (ML I) from Viscum album, cycloheximide, actinomycin D, and brefeldin A but also the thionins from Viscum album (viscotoxins; VT) generated reactive oxygen intermediates (ROI) and induced expression of newly described mitochondrial membrane proteins Apo2.7, however, with different kinetics. Apart from a rapid permeabilisation of cell membranes by the VT with swelling of mitochondria, loss of their cristae and ROI generation within 2-4 h, the majority of the cells may have received a distinct 'death signal' resulting in an induction of Apo2.7 molecules within 24 h. In contrast, protein synthesis/transport inhibition may signal for apoptosis within 24 h by decreasing distinct 'survival promotors' which remain to be characterised.

Annexin A5↗
PubMed1999

Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat.

Thionins are small basic peptides found in different plant species, which are known to exert cytotoxic properties. In addition, previous data indicated an activation of human granulocytes by thionins from European mistletoe (viscotoxins, VT). To extend these latter findings, we investigated the influence of VT and from thionins from wheat flour (purothionin) on human granulocytes by flow cytometry and tried to characterise the involved molecular structures and mechanisms. Phagocytosis was determined by incorporation of FITC-labelled Escherichia coli and respiratory burst by oxidation of dihydrorhodamine 123 to rhodamine 123. VT and purothionin significantly enhanced E. coli-stimulated phagocytosis and respiratory burst at 25 and 250 microgram/ml. Phagocytosis of damaged lymphocytes by granulocytes was detected by electron microscopy in the VT-stimulated (100 microgram/ml) but not in the control cultures. The poly-cationic structure of the intact molecule seems to be crucial, as evidenced by comparison of the burst and phagocytosis-enhancing effects induced by other poly-cationic (protamine sulphate, histone, poly-l-arginine, poly-l-lysine) and poly-anionic (poly-l-glutamic acid) peptides, while pore forming due to amphipathic properties seems to be less important. Ca2+ and Mg2+ could not inhibit VT-enhanced phagocytosis and, thus, could not inhibit binding of VT to granulocytes. In addition, verapamil at low concentrations inhibited VT activity, suggesting the involvement of Ca2+ channels for granulocyte activation by the VT. Similarly, thionins and histones in contrast to protamine sulphate induced cell death of granulocytes at 250 microgram/ml as demonstrated by an enhanced release of reactive oxygen intermediates in unstimulated granulocytes. From these data one may suggest that activity of VT is induced by strong unspecific ionic binding, probably followed by specific receptor binding, and thionins exhibit stimulatory and cytotoxic effects on immune cells, which have to be further characterised.

Antimicrobial Cationic Peptides↗
PubMed1999

Accidental cell death and generation of reactive oxygen intermediates in human lymphocytes induced by thionins from Viscum album L.

The cytotoxic mechanisms of thionins from Viscum album L., the viscotoxins, were investigated in human granulocytes and lymphocytes. The time course of viscotoxin effects indicate accidental cell death, i.e. membrane permeabilization, degradation of cytoplasm and chromatin, swelling of mitochondria with loss of their cristae, and generation of reactive oxygen intermediates within 1-2 h, followed by secondary apoptosis-associated events. The viscotoxin homologue purothionin from whole-wheat flour and viscotoxin B, however, did not induce cell death in cultured lymphocytes. Cytotoxicity of cationic and amphipathic viscotoxin was prevented only by cleavage of its disulphide bridges.

Apoptosis↗
PubMed1999

[Development of lymphocyte subsets in tumor patients after subcutaneous administration of mistletoe extracts].

OBJECTIVE: In order to exclude the possibility that mistletoe therapy may result in immunosuppression, as indicated by a significant reduction of defined lymphocyte subsets, PATIENTS AND METHODS: peripheral blood cells of 23 tumour patients were treated subcutaneously with increasing concentrations of aqueous mistletoe extracts (Helixor(R)). RESULTS AND CONCLUSIONS: Within an observation period of 7 months, the relative amount of lymphocytes and the number of natural killer (NK) cells increased while the number of lymphocyte subsets (i. e. CD19+ B cells, CD4+ T helper cells, CD8+ CD28- suppressor cells, CD8+ CD28+ cytotoxic cells) and the proportion of CD25+ (activated) cells within T cells showed a statistically remarkable trend; due to the multiple test problem of statistical evaluation this trend is not allowed to be termed significant. The leucocytes decreased insignificantly within the observation period. However, we were unable to verify a suggested increase of defined lymphocyte subsets within 2-3 months after the onset of mistletoe treatment. Nevertheless, for the parameters CD19+ B cells, CD4+ T helper cells, CD8+ cells, CD8+ CD28+ cytotoxic cells and CD16+/CD56+ NK cells we observed statistically remarkable peaks within die 2nd and 3rd month of therapy, confirming the hypothesis. The responses to the extracts were obviously interindividually different; the immune responses especially of patients with a lower number of peripheral T cells were less significant as compared to those of patients with adequate T cell numbers. Surprisingly, even an increase of the drug concentration >3 ng mistletoe lectin (as determined within the whole plant extract) per kg body weight enhanced the number of CD4+ T helper cells. A decreased immunological reaction on mistletoe extracts was shown especially for patients with a reduced number of peripheral T cells, whereas patients with normal T-cell number were more reactive.

Adult↗
PubMed1998

Induction of apoptosis by the N-acetyl-galactosamine-specific toxic lectin from Viscum album L. is associated with a decrease of nuclear p53 and Bcl-2 proteins and induction of telomeric associations.

The ribosome-inhibiting proteins from Viscum album L., i.e. the mistletoe lectins (ML), were recognized to induce apoptosis in various tumour cell lines and human lymphocytes. However, several aspects of ML-induced cell death are unclear. We report that the galNAc-binding ML III incubated with human lymphocytes mediates a very effective death signal resulting in the binding of Annexin-V and expression of mitochondrial membrane proteins Apo2.7, but also in an influx of the DNA intercalating dye propidium iodide. The addition of the ribosome-inhibiting protein Volkensin also induced Apo2.7 molecules, while Momordin, lacking a carbohydrate-binding chain, did not enter the cell membrane and thus did not affect the cells. However, we observed ML III to preferentially affect CD8+ cells with a memory phenotype (CD62L(lo)) as compared to their CD8+ CD62L(hi) counterparts, CD4+ T cells and CD19+ B cells. Furthermore, ML III did not induce sister chromatid exchange-inducing DNA lesions but reduced the intensity of telomeric signals, increased the frequencies of telomeric associations and C-anaphases and reduced nuclear Bcl-2 and p53 proteins. Whatever the exact mechanisms are, our results provide strong evidence that the ML III-mediated cytotoxicity involves distinct killing pathways, i.e. (1) primary cell death via an induction of apoptosis which may not be dependent on protein and/or RNA synthesis and may not involve p53 and Bcl-2 proteins and (2) a loss of telomeres resulting in chromosomal instability in the surviving cells which is incompatible with life. However, we cannot exclude the possibility that this effect is due to a decrease in nuclear p53 proteins.

Apoptosis↗
PubMed1998

[Vascularization of breast tumors: use of ultrasound contrast medium in evaluating tumor entity. Preliminary results].

PURPOSE: The objectives of the present study were to investigate the utility of an ultrasound echo enhancer in the evaluation of the dignity of breast tumors and to identify the best examination parameters. PATIENTS AND METHODS: 68 breast tumors in 61 female patients who were referred for operative tumor removal were examined by color-coded duplex sonography before and after administration of Levovist. The investigated parameters were: a) the degree of enhancement, b) the number of tumor vessels, c) the time to maximum enhancement, and d) the morphological pattern and course of vessels. RESULTS: With regard to parameters A, B, and C there were in part pronounced overlaps between malignant (n = 44) and benign (n = 24) lesions. The best differentiation was found for parameter D with a sensitivity of 95% and a specificity of 83%. In all previously operated patients a distinction between a postoperative scar (n = 8) and a tumor recurrence (n = 13) was possible. CONCLUSIONS: The use of Levovist leads to a clear improvement in the evaluation of dignity by duplex sonography. On the basis of our preliminary results, the characteristic pattern of vascular morphology and course is the best examination parameter. In particular, the otherwise difficult distinction between scar and recurrence appears to be an interesting application.

Adult↗
PubMed1998

Increased dermal carotenoid levels assessed by noninvasive reflection spectrophotometry correlate with serum levels in women ingesting Betatene.

beta-Carotene is being used as an oral sun protectant, and evidence indicates that carotenoids may protect human skin from light-induced lesions. However, limited information is available on the distribution and accumulation of beta-carotene in skin, especially with respect to various skin regions. With the use of reflection spectroscopy, we investigated the accumulation of total carotenoids in human skin after repeated supplementation of 12 women with beta-carotene from a natural source Betatene, an algal extract. After daily ingestion of 24 mg beta-carotene (in Betatene) for 12 wk, an increase in carotenoid skin levels was observed. Highest basal values were measured in skin of the forehead, palm of the hand and dorsal skin, with lower levels measured in skin of the arm and back of the hand. Upon treatment, increases in carotenoid skin levels were found in all areas as follows: 2.4-fold in forehead, 0.7-fold in dorsal skin, 2.2-fold in the palm of the hand, 17-fold on the back of the hand and 1.7-fold on the inside of the arm. After cessation of treatment, the carotenoid levels decreased in all skin areas. Serum beta-carotene levels were elevated upon treatment and correlated with carotenoid skin levels. Correlations for serum vs. skin from the palm of the hand (r = 0.94) and skin from the forehead (r = 0.89) were calculated, indicating that serum levels appeared to be a suitable indicator for carotenoid accumulation in specific regions of the skin. With doses of approximately 20-25 mg carotenoids/d, it is possible to raise dermal carotenoid levels.

Adult↗
PubMed1996

Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins.

Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously.

Apoptosis↗
PubMed1980

[Therapeutical aspects of the neuroblastoma (author's transl)].

Formation of the neuroblastoma, primary locations of the tumor, its mode of spreading and the incidence dependent on age are reported from 2055 cases. The prognosis, dependent on an early diagnosis, and the problems related to it are discussed. The actual therapeutic concepts as operation, radiation and chemical therapy for children and adults are represented. A well-differentiated combined schedule is recommended.

Adolescent↗
PubMed1977

[Analgesia with mild side effects].

The efficacy of nefopam, a novel analgesic agent, was compared to pentazocine in a double blind study in 40 cancer patients with chronic pain. Both drugs were administered orally for 10 days. Pain relief after nefopam was at least as good as after pentazocine. Side efftects after nefopam were different in nature and less frequent than after pentazocine; respiratory depression or sedation were no observed.

Analgesia↗
PubMed1976

[Radiation therapy of eyelid carcinomas].

Forty patients with histologically verified tumors of the eyelid, partly being pretreated surgically, were irradiated and reexamined. The irradiations were performed with an apparatus for surface therapy using soft rays. The radiation quality was between 55 and 100 kV, the dose between 3000 and 6000 rd. The single doses amounted to 300 or 400 rd. The rate of recurrences after primary irradiation of basaliomas was 5,5%, the rate of recovery 94,5%. The patients who underwent primary operation show a distinctly increased rate of recurrences. The percentage of complications was small, amounting to 8%. Primary irradiation is recommended for the treatment of stages T1 and T2 of eyelid tumors, the percentage of recovery being high and the number of complications small. Advanced stages ought to be treated according to the site and infiltration of the tumor either by the telecaesium apparatus under conditions of semi-deep therapy with use of a lead satellite for protection of the cristalline lens and with following soft-ray therapy, or by primary operation followed by radiation therapy.

Adenocarcinoma↗