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Biomedical subjects

M Bamberg

Publications and source records attributed to M Bamberg.

At least 91 records · Page 5Linked to original sources
PubMed1999

Impressive remission in a patient with locally advanced malignant pleural mesothelioma treated with gemcitabine.

The results of treatment of malignant pleural mesothelioma are quite unsatisfactory regardless of the substance or schedule employed. Although some activity is proved for anthracyclines, platinum compounds and alkylating substances, no chemotherapeutic regimen has emerged as a standard of care. Response rates documented in literature are between 10 and 20% for all these regimens. We report about a patient with locally advanced, unresectable pleural mesothelioma treated with the nucleoside analog gemcitabine (2,2-difluorodeoxycytidine). A 54-year-old male patient with unresectable pleural mesothelioma confirmed by thoracoscopic biopsy was treated with seven cycles of gemcitabine (1000 mg/m2 on day 1, 8 and 15) over a period of 36 weeks. Restaging by thoracic computed tomography (CT) scan was performed after 8, 20 and 36 weeks. At week 36 after beginning of treatment, the CT scan exhibited a substantial partial remission with a reduction of tumor volume of over 50%. The adverse effects of the therapy were very moderate with a hematotoxicity not exceeding WHO grade I and a mild 'flu-like syndrome' during the first three cycles which responded quite well to steroids. The compliance of the patient was excellent and his general condition improved significantly under therapy. Gemcitabine seems to be an active drug for the treatment of pleural mesothelioma. Compared to other active regimens it is normally very well tolerated by the patients. Because of these characteristics gemcitabine seems a suitable antineoplastic substance, especially in palliative settings. It would be worthwhile to test its activity in pleural mesotheliomas in controlled trials.

Antimetabolites, Antineoplastic↗
PubMed1999

Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89.

PURPOSE: A multicenter prospective trial was conducted (Maligue Keimzelltümoren [MAKEI] 83/86/89) to assess outcome in intracranial germinoma after treatment with radiotherapy alone at reduced doses. PATIENTS AND METHODS: Between 1983 and 1993, 60 patients with histologically (n = 58) or cytologically (n = 2) confirmed germinoma were enrolled onto the study. Patients received radiotherapy alone (craniospinal axis/local boost). In the MAKEI 83/86 study (involving 11 patients), the dose to the craniospinal axis was 36 Gy and the dose to the tumor region was 14 Gy. In the MAKEI 89 study (involving 49 patients), doses were 30 and 15 Gy, respectively. RESULTS: Median patient age was 13 years (range, 6 to 31 years). Complete remission was achieved in all patients. The estimated (Kaplan-Meier) 5-year relapse-free survival rate was 91.0% +/- 3.9% at a mean follow-up of 59.5 months (range, 3 to 180 months); the estimated overall survival rate was 93.7% +/- 3.6%. Relapse occurred in five patients 10 to 33 months (mean, 18.4 months) after diagnosis (one patient developed a spinal canal metastasis and underwent salvage radiotherapy and chemotherapy; four patients had metastases outside the CNS and underwent salvage chemotherapy alone). Four patients died: one died from disease, two died from therapy-related complications, and one committed suicide. Acute complications with long-lasting sequelae were tumor or surgery related (three cases of blindness, six of reduced vision, two of hemiparesis). Psychosocial development was normal in the majority of patients. CONCLUSION: Radiotherapy directed toward the craniospinal axis or tumor site alone at decreased dose levels is effective. To reduce the risk of late side effects, further attempts to decrease total doses are justified. In cases of recurrent disease, chemotherapy administered outside the CNS is the treatment of choice.

Adolescent↗
PubMed1998

Influence of light delivery on photodynamic synovectomy in an antigen-induced arthritis model for rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: Minimally invasive synovectomy techniques have been unsuccessful due to lack of selectivity. The purpose of this study was to evaluate the potential of photodynamic therapy to destroy diseased synovium in an antigen-induced arthritis model. STUDY DESIGN/MATERIALS AND METHODS: Three sets of experiments evaluated the biodistribution and treatment effects of Photofrin (PF) in rabbits with bilateral knee antigen-induced arthritis. The first set of experiments evaluated the biodistribution of PF in articular tissues of 30 rabbits from 6-72 hours after systemic injection of 2 mg/kg. In the second series of experiments, light was delivered to the knee joint via cleaved optical fibers, whereas for the third, light was delivered via a 600 microm diffusion tip fiber. Tissues were harvested at 2 and 4 weeks posttreatment. RESULTS: The biodistribution experiments demonstrated maximal uptake in inflamed synovium at 48 hours and a lack of uptake in normal tissues. With bare cleaved fibers, necrosis was observed in one specimen at 2 weeks and was absent in all specimens at 4 weeks. In the third experiment, synovial necrosis was observed in 3 of 7 specimens at 2 weeks and 3 of 8 at 4 weeks. No damage to articular cartilage or periarticular tissues was seen with either mode of light delivery. CONCLUSION: These studies indicate that selective destruction of synovium can be achieved with PF and suggest that optimization of light delivery techniques will play an important role in development of this new technique.

Analysis of Variance↗
PubMed1998

Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy.

OBJECTIVE: This retrospective study was conducted to document the incidence and location of recurrences as well as the rate of side effects following low-dose postoperative high-dose-rate (HDR) brachytherapy in patients with endometrial carcinoma. METHODS: From 1987 to 1993, 122 patients with moderate-risk (78) and high-risk (44) endometrial carcinoma underwent adjuvant vaginal irradiation. All patients received three fractions of 7 Gy specified on the surface of the vaginal cylinder. RESULTS: Relapses occurred in 12 (9. 8%) patients on average after 25.6 months. Seven (5.7%) patients had a sole pelvic recurrence; in 2 (1.6%) of those the relapse was located in the vagina only. Three (2.5%) patients had a pelvic relapse combined with distant metastases. Distant metastases alone were diagnosed in 2 (1.6%) patients. A tumor recurrence was diagnosed in 3 of 78 (3.8%) patients with moderate-risk disease and in 9 of 44 (20.5%) patients with high-risk disease. The estimated 5-year relapse-free survival was 94% for patients with moderate-risk and 74% for patients with high-risk tumors (P = 0.004). Neither severe nor chronic complications were noted. CONCLUSION: Even low doses of HDR brachytherapy seem sufficient for excellent vaginal disease control in moderate-risk disease. In advanced tumors combined radiation therapy is warranted for improved pelvic disease control.

Aged↗
PubMed1998

[Testicular intraepithelial neoplasms (TIN). An indication for radiotherapy?].

BACKGROUND: Testicular intraepithelial neoplasia (TIN), synonymous for carcinoma in situ of the testis, is a rarely observed preinvasive neoplasia located within the germinative epithelium. According to the current knowledge of the biology of TIN, it is the common precursor of all testicular germ cell neoplasms except spermatocytic seminoma. MATERIAL AND METHODS: This report provides a review of histopathology, epidemiology and diagnostic procedures for TIN and discusses the therapeutic options with particular respect to radiooncological aspects. RESULTS: TIN has a 70% rate of progression to invasive cancer within 7 years. Depending on the individual therapeutic setting surgery, chemotherapy and radiotherapy are alternative treatment modalities. In case of TIN in a single testis or bilateral TIN, local radiotherapy is the standard procedure. With 20 Gy recommended as standard dose in Germany, radiotherapy yields safe eradication of TIN. However, some of the patients show significantly reduced synthesis of testicular androgens. With respect to sporadic reports in the literature, total doses well below 20 Gy might be equally efficient to treat TIN safely. Yet, up to date neither the minimum dose for efficient treatment nor the toxicity profile after consecutive chemo-radiotherapy has been established. CONCLUSIONS: The currently recommended standard dose of 20 Gy in Germany is probably in excess of the minimum dose needed for safe eradication of TIN. Thus, new radiooncological strategies should aim at reducing the total dose of treatment in order to minimize late side effects while maintaining the high efficacy of radiotherapy. This topic is under investigation in a multicenter clinical trial.

Antineoplastic Agents↗
PubMed1998

Differentiation state of skin fibroblast cultures versus risk of subcutaneous fibrosis after radiotherapy.

BACKGROUND AND PURPOSE: There is increasing evidence for patient-to-patient variation in the response of normal tissue to radiotherapy. Recently, it has been suggested that accumulation of functional fibrocytes may be a key step in the development of radiation-induced fibrosis. Therefore, we have examined a possible relationship between the differentiation state of untreated fibroblasts and the risk of radiation-induced subcutaneous fibrosis in individual patients. MATERIALS AND METHODS: We used skin fibroblast cultures isolated from eight postmastectomy radiotherapy patients whose individual clinical radiosensitivity was assessed by the mean excess risk of fibrosis. Different types of potentially mitotic progenitor fibroblasts (MF) and postmitotic functional fibrocytes (PMF) in the terminal differentiation lineage, MFI --> MFII --> MFIII --> PMF, were scored morphologically in clonal culture. Progression of differentiation was quantified by the ratio L/E of colony-forming late (MFIII and late MFII) and early (MFI and early MFII) progenitors. RESULTS: We observed a correlation between the ratio L/E and the mean risk of fibrosis (rs = 0.743, P = 0.03), indicating an approximately 10-fold increase in L/E with an increasing risk of fibrosis. This was paralleled by a decreasing trend in the absolute numbers of early progenitor types. By contrast, there was no significant correlation between the plating efficiency and the risk of fibrosis. CONCLUSIONS: The data suggest that the risk of fibrosis increases with the progression of the differentiation of untreated progenitor fibroblasts, indicating that the progression of fibroblast differentiation may be a co-factor in the development of radiation-induced fibrosis. If this hypothesis is validated, it provides a rationale for a novel predictive test to identify patients with an increased risk of subcutaneous fibrosis.

Adult↗
PubMed1998

The suppression of heterotopic ossifications: radiation versus NSAID therapy--a prospective study.

This prospective, randomized study compares the effect of postoperative irradiation and nonsteroidal anti-inflammatory drug (NSAID) therapy on the prevention of heterotopic ossifications after the implantation of a total hip endoprosthesis. A total of 154 operations were performed; one group of patients underwent radiation treatment of 3 x 3.3 Gy, and the other group took 3 x 50 mg of diclofenac per day over a period of 3 weeks. Average age, sex, preoperative diagnosis, and risk factors were similar in both groups. Postoperative radiation began on average 2.9 days after operation, and the radiation therapy was finished on average within 3.8 days. NSAID prophylaxis was begun on the first postoperative day. Heterotopic ossifications occurred in two of the patients who had undergone postoperative prophylaxis by radiation. In both cases, the ossification was Brooker I, and there was no functional impairment. There were no ossifications of Brooker II-IV in this group. One patient had a Staphylococcus epidermidis infection, and fistula revision had to be carried out; the prosthesis could be left in place. In the group treated with NSAID, 16 heterotopic ossifications stage Brooker I and 2 stage Brooker II could be detected. Eleven patients stopped the treatment because of gastrointestinal problems. Both postoperative radiation and NSAID therapy have proved to be effective prophylactic methods. In direct comparison, radiation prophylaxis by 3 x 3.3 Gy proved to be slightly more successful than NSAID prophylaxis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Molecular and cellular basis of radiation fibrosis.

PURPOSE: Recent data from the literature and the experimental work of the authors clearly indicate that TGF-beta1 is a key modulator of cellular events, for example, induction of terminal differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogenously added TGF-beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. MATERIALS AND METHODS: Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. RESULTS: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF-beta1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF-beta1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF-beta1. CONCLUSIONS: The data presented indicate that TGF-beta1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.

Animals↗
PubMed1998

Mitomycin C-related hemolytic uremic syndrome in cancer patients.

In rare cases mitomycin C (MMC) may induce cancer-associated hemolytic uremic syndrome, which is characterized by hemolytic anemia, thrombocytopenia and progressive renal failure. Treatment possibilities of this multisystem disease up to now remain disappointing. We report a case of MMC-related hemolytic uremic syndrome, and discuss the etiologic parameters, clinical aspects, prognosis and treatment modalities of this severe syndrome.

Adenocarcinoma↗
PubMed1998

Photodynamic synovectomy using benzoporphyrin derivative in an antigen-induced arthritis model for rheumatoid arthritis.

Experimental photodynamic therapy (PDT) has recently been adapted for the treatment of inflammatory and rheumatoid arthritis. The biodistribution of benzoporphyrin derivative monoacid ring A (BPD-MA) and the effect of percutaneous light activation via intra-articular bare cleaved optical fibers was investigated using a rabbit-antigen-induced arthritis model. Qualitative evaluation of intra-articular photosensitizer clearance was performed with laser-induced fluorescence from 0 to 6 h following intravenous injection. The compound was rapidly taken up within the joint and then cleared steadily over the 6 h interval. Biodistribution was determined by fluorescence microscopy and spectrofluoroscopic extraction techniques 3 h following intravenous injection of 2 mg/kg BPD-MA. The biodistribution study demonstrated elevated levels of BPD-MA in synovium (0.35 microgram/g) and muscle (0.35 microgram/g). Fluorescence microscopy demonstrated presence of the compound within pathologic synovium but absence of the photosensitizer within meniscus, ligament, bone and articular cartilage. Tissue effects were evaluated histologically at 2 and 4 weeks posttreatment. BPD-MA-mediated PDT caused synovial necrosis in the region of light activation in 50% of treatment knees at 2 weeks and 43% at 4 weeks. No damage to nonpathologic tissues was observed. These studies indicate that selective destruction of synovium can be achieved by the light-activated photosensitizing agent BPD-MA without damage to articular cartilage or periarticular soft tissues. PDT needs to be further evaluated to optimize treatment parameters to provide for a new minimally invasive synovectomy technique.

Animals↗
PubMed1998

Radiation-induced apoptosis in human lymphocytes and lymphoma cells critically relies on the up-regulation of CD95/Fas/APO-1 ligand.

Ionizing radiation is known to induce death by apoptosis in malignant and nonmalignant human lymphocytes. The mechanism which initiates the induction of apoptosis has not been identified. Here we demonstrate that a radiation-induced up-regulation of CD95/Fas/APO-1 ligand (CD95-L) is involved in the induction of apoptosis in lymphocytes and lymphoma cells. Using antibodies against CD95-L, we detected a rapid and persistent up-regulation of CD95-L in Jurkat cells and blood lymphocytes after irradiation. Blocking of interactions between CD95/Fas/APO-1 and CD95-L with inhibitory antibodies reduces apoptosis after irradiation. The hypothesis that an interaction between CD95 and CD95-L is involved in radiation-induced apoptosis is supported by the finding that only peripheral blood lymphocytes that are stimulated with interleukin 2 for 5 days and thus are rendered sensitive to CD95-L show pronounced levels of apoptosis in response to low radiation doses, whereas resting peripheral blood lymphocytes show very low levels of apoptosis after treatment with CD95-L and radiation. The finding that the caspase FLICE is degraded proteolytically after irradiation and the observation of a radiation-induced CD95 receptor capping confirm the functional activation of the CD95 receptor.

Apoptosis↗
PubMed1998

The role of cytokines in the development of normal-tissue reactions after radiotherapy.

BACKGROUND: Cytokines are important for signaling between cells and tissues and constitute a humoral component of the response of cells and tissues to radiotherapy. Although several cytokines have been implicated in mediating radiation-induced reactions of normal tissues, the mechanisms are only beginning to be elucidated. METHODS: Published data on radiation-induced cytokine expression from cell culture, experimental and clinical studies are reviewed. Current models of cytokine-mediated multicellular interactions in radiation-induced reactions of the lung, skin and intestinal mucosa are presented. RESULTS AND CONCLUSION: The major cytokines in the radiation response of non-hemopoietic tissues include IL-6, IL-1, INF alpha and TGF beta. Different cell types interact via cytokines in a complex network of effector and receptor cells, including inflammatory cells, tissue-specific functional cells and fibroblasts. TGF beta appears to be of particular importance in the development of late reactions such as fibrosis.

Animals↗
PubMed1998

Clinical impact of predictive assays for acute and late radiation morbidity.

BACKGROUND: Clinically reliable predictive assays for normal tissue radiation sensitivity would help to avoid severe radiation induced morbidity and result in individualized dose prescriptions. Profound differences of individual fibroblast and lymphocyte radiation sensitivity in vitro have been documented in patients with certain genetic syndromes but also in patients without known genetic disorders. The following review evaluates whether fibroblast or lymphocyte radiation sensitivity measured in vitro correlates with the degree of acute and late radiation induced morbidity. RESULTS: Acute radiation side effects and lymphocyte sensitivity has been investigated in 2 studies. One of them reported an insecure correlation, the other no correlation at all. Fibroblast radiation sensitivity and the extent of acute radiation induced side effects on skin and mucosal sites has been compared in a total of 5 studies. None of these studies found a consistent significant correlation. Lymphocyte radiation sensitivity and late effects have been studied by 2 institutions. Late radiation induced skin and mucosal changes did not correlate with lymphocyte sensitivity in head and neck cancer patients, whereas in breast cancer patients a weak (R2 = 0.06) correlation between the degree of late skin reactions and lymphocyte sensitivity was observed. Late skin or mucosal radiation reactions and fibroblast sensitivity were examined by 5 research groups. Data analysis revealed significant correlations or at least a trend towards a significant correlation in all studies. The quality of the reported correlations expressed as R2 ranged from 0.13 to 0.60, indicating a low predictive value. CONCLUSIONS: Lymphocyte radiation sensitivity as measured by currently available assays does not or only poorly correlate with acute and late effects of radiation in patients, precluding predictive tests based on lymphocyte sensitivity. Fibroblast radiation sensitivity does not correlate with acute but generally correlates with late radiation morbidity. The quality of the later correlation is insufficient for a reliable predictive test with currently available methods to determine cellular radiation sensitivity.

Breast Neoplasms↗
PubMed1998

Radiation-induced gastrointestinal toxicity. Pathophysiology, approaches to treatment and prophylaxis.

BACKGROUND: Gastrointestinal toxicity is frequently observed during radiotherapy of malignancies in the abdomen and pelvis. The proposed pathophysiology of radiation enteritis is complex and a variety of different treatment strategies have been suggested for the management of acute radiation-induced diarrhea. MATERIAL AND METHODS: Data are presented from an extensive review of the current literature. RESULTS: Radiation-induced diarrhea results from a variety of different pathophysiological mechanisms including malabsorption of bile salts and lactose, imbalances in local bacterial flora and changes in the intestinal patterns of motility. Up to date acute radiation diarrhea is predominantly treated symptomatically using opioide derivates (loperamide) or adsorbants of bile salts such as smectite. Clinical trials have been performed using L. acidophilus, smectite or sucralfate for diarrhea prophylaxis with moderate reduction of acute symptoms. CONCLUSIONS: Further evaluation of strategies for diarrhea prophylaxis is warranted. Due to the complex nature of radiation enteritis a multimodal approach taking into account alterations in intestinal motility patterns, malabsorption of bile salts and an imbalance of mucosal bacterial flora may offer new perspectives.

Abdominal Neoplasms↗