[Academy for Pneumological Vocational Training (APFW) e.V].
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Biomedical subjects
Publications and source records attributed to D Rohde.
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By thermal decarboxylation of N-arylated 2-aminothiophene-5-cacrboxylates, a versatile, heavy-metal free method for preparing the title compounds as new class of highly reactive and easily oxidable, amorphous glass forming molecules has been elaborated.
PURPOSE: To report on the nephron-sparing, percutaneous ablation of a large renal cell carcinoma by combined superselective embolization and percutaneous radiofrequency ablation. MATERIALS AND METHODS: A 5 cm renal cell carcinoma of a 43-year-old drug abusing male with serologically proven HIV, hepatitis B and C infection, who refused surgery, was superselectively embolized using microspheres (size: 500 - 700 microm) and a platinum coil under local anesthesia. Percutaneous radiofrequency ablation using a 7 F LeVeen probe (size of expanded probe tip: 40 mm) and a 200 Watt generator was performed one day after transcatheter embolization under general anesthesia. RESULTS: The combined treatment resulted in complete destruction of the tumor without relevant damage of the surrounding healthy renal tissue. The patient was discharged 24 hours after RF ablation. No complications like urinary leaks or fistulas were observed and follow up CT one day and 4 weeks after the radiofrequency intervention revealed no signs of residual tumor growth. CONCLUSION: The combined transcatheter embolization and percutaneous radiofrequency ablation of renal cell carcinoma has proved technically feasible, effective, and safe in this patient. It may be offered as an alternative treatment to partial or radical nephrectomy under certain circumstances.
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The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies.
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This in vitro study aimed to investigate the cytotoxic activity of 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)-mitomycin C (KW-2149) versus mitomycin C (MMC) against cell lines from human transitional cell carcinoma (TCC). Direct cytotoxicity of the two drugs was measured employing a colorimetric cytotoxicity assay on chemonaive and chemoresistant cancer cell populations. The results revealed that all cell lines (n = 19) were significantly more inhibited by treatment (2 h, 96 h) with KW-2149 than by MMC (P < 0.03-0.001). pH 6.0 decreased the stronger activity of KW-2149 (P < 0.013-0.004). Creatinine > or =10 mmol/l and nitrosourea > or =100 mg/l also inhibited the activity of KW-2149 significantly. Tumor cells with relative drug-resistance against MMC (RT112-MMC: 55-fold) exerted minor cross-resistance to KW-2149 (fourfold). In conclusion, the present in vitro data suggest KW-2149 to be a superior drug for intravesical therapy of patients with primary or recurrent superficial bladder carcinoma. Since pH and concentrations of creatinine and nitrosourea influence the activity of KW-2149, patients are supposed to profit from neutralizing the urinary pH and enhanced diureses.
Residual tumor, tumor progression or relapse after chemotherapy of patients with advanced or metastasized transitional cell carcinoma of the bladder (TCCB) are suggested to reflect intrinsic drug resistance of cancer cells, or the development of chemotherapy-resistant tumor cell populations. The present study aimed to establish drug-resistant subculture cell lines from human TCCB, selected for anticancer drugs, administered in the cisplatin, methotrexate and vinblastine (CMV) polychemotherapy protocol. Tumor cells from chemonaive cell lines of human TCCB (HT1376, TCCSUP) have been exposed to progressively increasing concentrations of cis-diamminedichloroplatinum (II) (CDDP), methotrexate (MTX), vinblastine (VBL) or etoposide (VP16). The resulting drug-resistant subculture cell lines (HT1376-CDDP, HT1376-MTX, HT1376-VBL, HT1376-VP, TCCSUP-CDDP, TCCSUP-MTX, TCCSUP-VBL, TCCSUP-VP) were analyzed with regard to the achieved resistance factor (RF) for the inductive anticancer agent, the acquisition of cross-resistance, DNA content, cell cycle distribution and cellular morphology. Parental HT1376 cells were intrinsically less sensitive to all anticancer drugs (1.7-50x), compared with TCCSUP cells. Relative resistance against the inductive anticancer agents was similar for the final drug-resistant subculture cell lines of both parental cell lines concerning CDDP and VP-16 (RF: 4-5x), but were reciprocal for MTX and VBL, respectively. MTX led to much stronger resistance (RF > 200) than the other drugs (RF < 10). Pleiotropic cross-resistances were observed in six out of eight (75%) drug-resistant subculture cell lines. Highest RF (50-500x) and frequency of cross-resistance (five of six cell lines) occured for MTX, and the least from exposure to CDDP (one of six cell lines). Overall, the results corroborated the central role of CDDP against urothelial carcinoma whereas repetitive applications of MTX appeared to be a doubtful strategy. Moreover, the experiments provide the largest panel so far of drug-resistant cell lines of human TCCB. They represent an appropriate tool for basic research on drug-resistance mechanisms, for the development and screening of future anticancer drugs or to elaborate strategies to overcome drug resistance for those patients who ultimately fail to respond to standard chemotherapy.
Occurrence of metachronous primary malignant neoplasms (PMN) in five or more different organs and tissue of the same patient is a very rare event. The present paper reports on a female patient who experienced Hodgkin's disease of nodular sclerotic type (stage IV), carcinoma of the cervix uteri (stage I), adenocarcinoma of the rectum (Dukes A), and a well-differentiated adenocarcinoma of the stomach (pT1) before she demonstrated multicentric transitional cell carcinoma of the renal pelvis and ureter (pT3b G2-3) and of the bladder (pTa G2). Although an increased inherent predisposition of the patient to exhibit those neoplasms, similar to Lynch syndrome II, is to be discussed, her previous treatments with cyclophosphamide and external radiotherapy are likely to explain at least the occurrence of urothelial cancer. However, a report on renal pelvis and ureteral cancer induced by cyclophosphamide or irradiation is a rarity in itself.
The present in vitro study on three human renal cell carcinoma (RCC) cell lines (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine), vinblastine (VBL), rhu-interferon-alpha (IFN-alpha) and rhu-interferon-gamma (IFN-gamma) alone or in combinations. The cytotoxicity was measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses were made from cells being continuously long-term (4 weeks) or short-term (4 h) with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the chemotherapeutic agents. dFdC was more cytotoxic against ACHN and A-498 cells compared to VBL. Pre-treatment with IFN-alpha enhanced growth inhibition caused by dFdC (4/4 cell lines) and VBL (2/3 cell lines), and was more effective than IFN-gamma. Pre-exposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC. A-498 cells achieved a decreased sensitivity to dFdC and VBL after pre-exposure to IFN-gamma. The resistance of newly established dFdC-resistant SN12C cells (23-times) decreased when pre-treated with IFN-alpha. The data demonstrate efficacy of dFdC in human RCC at concentrations below clinically achievable doses. dFdC was more effective compared to VBL. Combined therapy preferentially with IFN-alpha increased cytotoxicity of dFdC in vitro. In vivo studies in nude mice xenografts are under investigation to support these observations.
Recent in vitro experiments indicated strong activity of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) in human renal cell carcinoma (RCC) cell lines and an increase of efficacy by combined application of interferon (IFN). In the present study, nude mice with xenografts from ACHN- or SN12C cells were treated by dFdC, dFdC plus IFN-alpha or vinblastine (VBL) plus IFN-alpha. ACHN-xenografts were significantly more inhibited by dFdC+/-IFN-alpha than by VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional treatment with IFN-alpha shortened the time to commencement of tumor remission and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metastases compared to untreated animals. Survival was significantly prolonged by dFdC+/-IFN-alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In conclusion, experimental data confirm dFdC as a superior drug against human RCC compared to VBL. Combined therapy with IFN-alpha increased the efficacy of dFdC in terms of tumor response in immunodeficient nude mice, thus clinical studies are strongly recommended in patients with metastatic renal cell carcinoma.
This study aimed to investigate local immunotherapy with Nocardia rubra cell wall skeleton (N-CWS) and bacille-Calmette-Guerin (BCG) in chemically induced rat bladder carcinoma. After being fed with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine for 26 weeks, female Wistar rats were treated once a week by intravesical instillation of 100 microg N-CWS or 5 x 10(6) Colony-Forming Units (CFU) BCG. Tissue specimens were obtained 4 h after the ninth instillation and analyzed by reverse transcription polymerase chain reaction (RT-PCR) for mRNA expression of rat cytokines. The analysis showed high expression of interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha, IL-2, and interferon (IFN)-tau in BCG (7/7, 7/7, 7/7, 5/7) and N-CWS (9/9, 9/9, 8/9, 8/9) treated tumors in comparison to low expression in controls (3/9, 0/9, 3/9, 3/9). Interestingly, intravesical instillation of N-CWS tended to be less effective at preventing local invasion of the tumors. It is speculated that this difference may result from a more strongly induced expression of T-helper cell-derived lymphokines (IL-2, IFN-tau) by BCG.
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Case management has been the preferred method of helping persons with mental illness live in the community. This report examines the historical development of case management practice over the past 30 years. The analysis revealed that evolutionary growth in case management developed in response to expansion of community mental health services rather than consumer interests to improve their quality of life. Consequently, this reveals itself in the lack of outcome criteria needed to measure case management effectiveness. Currently, the concept of case management is undergoing a revolutionary paradigm shift that is "consumer-driven" and responds to consumer concerns. However, as mental health care costs rise within a rapidly growing community mental health care system, managed care is being implemented as a method to contain these rising costs. Because of major differences in philosophical underpinnings, developments in support of public mental health managed care may jeopardize the genesis of consumer-driven case management by supporting case management models that reflect managed care ideology.
OBJECTIVE: The occurrence of autoimmune diseases or deterioration of pre-existing disorders has recently been described after cytokine treatment. The present report gives evidence for acquired myasthenia gravis induced by externally administered interferon-alpha and interleukin-2 in a patient with metastasized renal cell carcinoma. Electromyographic investigations did not reveal generalised myasthenia gravis. However, a highly elevated titre of antibodies against the human acetylcholine receptor and a significant improvement in clinical symptoms during therapy with anticholinesterase drugs, combined with a decremental response in electronystagmography, indicated an intermittent mainly oculo-bulbar form of myasthenia gravis.
The culture of nursing education is a major influence in transforming student nurses' perceptions of mental illness and nurse educators are the primary facilitators in this process. Undergraduate nursing students' perceptions of mental illness change positively, however, it has not been understood how these changes occur. This pilot study extends understanding of how 22 undergraduate psychiatric nursing students' perceptions of mental illness became transformed during the course of one semester. The author analyzed student narratives using Heideggerian Hermeneutics. Five students, who wrote narratives, read a manuscript discussing the constitutive pattern and the relational themes and consensually validated the interpretation. The constitutive pattern that emerged is the Uncovering of Mental Illness. Three relational themes were identified that contributed to, and led to the development of the constitutive pattern. The three themes are (1) uncovering others' sameness through differences, (2) coming face-to-face with mental illness, and (3) the staff nurse influence in the uncovering process. In addition to increasing understanding of perceptual transformation, the findings from this interpretation suggest that nurse educators can guide students in the development of therapeutic relationships by facilitating the uncovering process.
Regulation of haemopoiesis is closely mediated by a number of growth factors in the marrow microenvironment. The identification of the cell type secreting these regulatory polypeptides is difficult due to the heterogeneity of bone marrow cells. To analyse the release of haemopoietic growth factors by normal human bone marrow cells at the single cell level, we employed the reverse haemolytic plaque assay (RHPA). Freshly isolated human marrow cells were examined for the release of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6 and granulocyte-monocyte colony stimulating factor (GM-CSF). In order to identify various cytokine-secreting cell types, the RHPA was combined with immunocytochemical or enzymatic staining. The total of secreting marrow cells as well as the amount of several secretory haemopoietic subpopulations could be determined with this technique under various conditions. Following incubation with pure serum-free medium without addition of any mediator, only few cells secreting either IL-1 alpha, IL-3, IL-6 or GM-CSF could be observed. After 2 h incubation with recombinant human-IL-1 alpha (rhIL-1 alpha) (10.0 ng/ml) or rhGM-CSF (10.0 pg/ml) the number of cytokine-secreting cells significantly increased for all secretory products tested. Using cytochemical staining reactions, we were able to identify 55% of all cells secreting a specific cytokine. Glycophorin C-positive erythropoietic cells turned out to be the largest fraction (up to 89%) of cytokine-releasing haemopoietic cells, followed by neutrophil granulocytes (between 6 and 48%), and monocytes/macrophages (between 4 and 23%). Only few CD 61-positive cytokine-secreting megakaryocytes could be detected. Dose- and time-dependent kinetics after stimulation with rhGM-CSF revealed that the bulk of secretory activity originates from haemopoietic or rather from erythropoietic cells following low level stimulation and after short stimulation time. Thus, our data are in keeping with the assumption, that especially erythropoietic cells are producing a repertoire of cytokines that is thought to exhibit regulatory functions within marrow microenvironment. In the present study the RHPA is presented as an appropriate tool for measuring cytokine release not only of cells of the haematopoietic system but also of other tissues, for example solid tumours or malignant lymphomas.
The aim of this study was to analyse N-butyl-n-butanol-4-nitrosamine (BBN)-induced alterations of the urothelium in rats concerning its content of phosphorus, sulphur, chlorine, potassium and calcium using electron microscopic X-ray microanalysis (REM analysis). The following histopathological findings of the bladder mucosa were discovered after exposure to BBN: normal urothelium (n = 36); focal epithelial proliferations (n = 12) following 6-12 week's exposure; epithelial hyperplasia (n = 8) after urothelial carcinoma (n = 4) following 12 weeks' exposure. The observed phosphorus/sulphur and phosphorus/calcium ratios based on REM analysis did not show any statistical correlation with the morphological changes classified by light microscopy. Our data do not support the hypothesis raised by other investigators that an increase in phosphorus content or phosphorus/sulphur or phosphorus/calcium ratio could indicate early neoplastic transformations of urothelial cells as "tumor markers".