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C Sebesta

Publications and source records attributed to C Sebesta.

At least 19 recordsLinked to original sources
PubMed2001

Successful treatment of invasive mould infection affecting lung and brain in an adult suffering from acute leukaemia.

We describe in detail a 67-yr-old woman who was treated with a cytostatic combination chemotherapy for newly diagnosed common-acute lymphoblastic leukaemia. At the end of induction therapy, the patient acquired invasive mould infection affecting lung and brain. The patient entered complete remission of her leukaemia. Treatment with liposomal amphotericin B was initiated along with surgical excision of the fungal brain abscess. Intrathecal instillation of amphotericin B deoxycholate was started using an Ommaya reservoir because of an anatomical connection between the postoperative cavity and the ventricle. Full dose cytostatic chemotherapy was continued with little delay. A computerised tomography scan of the chest performed 2 months later revealed no fungal abscesses. Magnetic resonance imaging of the brain did not reveal any fungal manifestation. During maintenance therapy/week 69, the patient relapsed from leukaemia. High doses of intravenous liposomal amphotericin B were administered prophylactically. The patient's leukaemia proved refractory to reinduction chemotherapy and the patient died from pneumonia 8 wk later. Post mortem microbiological investigation and histopathological examination of lung and brain tissue did not reveal any macroscopical or microscopical fungal manifestations. This case underlines the feasibility and successful application of combined antileukaemic, antifungal and surgical therapy in a patient with acute leukaemia.

Aged↗
PubMed2000

Elevation of plasma prolactin in patients undergoing autologous blood stem-cell transplantation for breast cancer: is its modulation a step toward posttransplant immunotherapy?

Prolactin is a suspected promotor of breast cancer cell growth, and it shares pleiotropic immunoregulatory properties. We studied plasma prolactin and its drug-induced modulation in 20 women with breast cancer undergoing high-dose chemotherapy and autologous blood stem-cell transplantation. Plasma prolactin levels were serially assayed before and during conditioning and within and beyond 30 days after transplant. Before transplant, prolactin plasma levels were in the age-adjusted range of normal women. During conditioning and within 30 days after transplant, prolactin levels increased in all patients (p < 0.0001), but remained in the normal range. Antiemetic drugs such as metoclopramide and phenothiazines, known to enhance pituitary prolactin secretion, further elevated prolactin plasma levels (p < 0.00001). Patients remaining in continuous complete remission after transplant (median follow-up, 3 years) disclosed higher prolactin levels compared with those obtaining only partial remission or ensuing early relapse. Prolactin levels are regularly elevated during conditioning and within 30 days after autologous transplantation for breast cancer. Further elevations of prolactin plasma levels are induced by metoclopramide and other antiemetic drugs. Elevated plasma prolactin had no adverse effect on disease-free survival after transplant. We propose to investigate further the upregulation of prolactin after transplant aiming to induce a posttransplant consolidative immune reaction.

Adult↗
PubMed2000

Serum protein 90K/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection.

The serum protein designated 90K/Mac-2BP has been found at elevated concentrations in the sera of patients with various types of cancer and viral infections. The importance of the 90K/Mac-2BP serum concentrations in predicting the response towards interferon-alpha treatment for hepatitis C virus (HCV) infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to monitor the serum concentrations of this protein in our HCV-positive patients. Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac-2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent correlation that was proved rather to be a strong dependence of 90K/Mac-2BP concentrations on disease severity/duration, which increases with age. Multiple correlation analysis demonstrated the independent nature of 90K/Mac-2BP concentrations, underscoring the potential high utility of this new marker. Our data corroborate the potential of the scavenger receptor family protein 90K/Mac-2BP as an independent predictor of disease severity during HCV infection.

Adolescent↗
PubMed2000

[Hepatitis C].

Explore the source record for details and available documents.

Antiviral Agents↗
PubMed2000

[Clinical aspects, course and extrahepatic manifestations of hepatitis C].

Hepatitis C virus infection occasionally causes acute icteric hepatitis. However, primary infection is usually asymptomatic. Viral clearance occurs only in 20%; most patients develop a chronic hepatitis, which tends to be hardly symptomatic for many years. The risk of progression to cirrhosis, hepatocellular carcinoma and end-stage liver disease is associated with the severity of histopathological changes, and is increased by additional factors, such as excessive alcohol intake or coinfection with hepatitis B virus and HIV. Immunologically mediated extrahepatic manifestations of hepatitis C, in particular essential mixed cryoglobulinemia, can often be observed. Occasionally, they lead to fatal complications.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Laboratory diagnosis of hepatitis C virus infection].

In Austria, the prevalence of hepatitis C virus infections is 0.7% (17). Exclusion of a putative infection as well as diagnosis and continuous monitoring of HCV-disease produce considerable costs for the health system. How many and which patients with HCV infection will acquire life-threatening complications is by far not clear. Also, the causes for viral persistence and liver-complications remain obscure. For certain, complex interactions of viral and immunological mechanisms will determine the individual outcome of the disease (1). These considerations pose decisive demands on clinical diagnostics for HCV infections to be dealt with in detail: methods for qualitative detection of an infection as well as for analysis of subtypes and for quantitative determination of viral copies; monitoring of therapy; estimation of the progress of the disease and/or efficacy of therapy.

Antiviral Agents↗
PubMed2000

[High dosage therapy and autologous peripheral stem cell transplantation in breast carcinoma].

42 breast cancer patients were treated by high-dose chemotherapy (HDC) and autologous peripheral stem-cell transplantation (ASTx) in the Donauspital between 1992 and 1999. 24 patients had stage II/III breast cancer with high risk for relapse. The other 18 patients underwent HDC and ASTx in chemosensitive stage IV. After previous conventional chemotherapy peripheral stem-cells were harvested by one cycle of mobilisation chemotherapy (epirubicin/taxol, FEC 120 or cyclophosphamide) followed by cytokine stimulation. 16 patients were treated by a tandem transplantation (conditioning protocol for 1st ASTx was melphalan 200 mg/m2 and for 2nd transplant it was CTC: cyclophosphamide 6 g/m2; thiotepa 500 mg/m2; carboplatin 800 mg/m2). The other 26 patients received one HDC with CTC as conditioning protocol. The HDC was well tolerated by all patients, there was no transplant-related mortality. The median survival and the progression-free survival (PFS) after HDC and ASTx in stage IV breast cancer patients were 28 and 11 months, respectively. The median survival and PFS were not yet reached in stage II/III patients after 55 months. The actuarial survival and PFS in that patient group were 70% after 55 months. Our data confirm the low risk and good efficacy of HDC and ASTx in breast cancer patients. Nevertheless randomised studies are necessary to evaluate the importance of HDC compared to intensified conventional protocols without ASTx.

Adult↗
PubMed2000

[High dosage therapy with stem cell transplantation in neuroendocrine carcinoma].

Neuroendocrine carcinoma and small-cell lung cancer (SCLC) are highly responsive to chemo- and radiotherapy. Nevertheless, most patients (pts.) experience relapse. At the 2nd department of medicine in the Donauspital, 4 pts. with neuroendocrine carcinomas of different primary sites underwent high-dose chemotherapy with autologous stem-cell transplantation (ASTx). Pt. 1 suffered from neuroendocrine lung cancer, pt. 2 from a small-cell carcinoma of the pancreas. Pt. 3 had a metastatic small-cell abdominal bulky tumor and pt. 4 presented with neuroendocrine carcinoma of the prostate. After 4-6 cycles induction chemotherapy pts. were consolidated with 1 cycle of HDCht and ASTx. Prior to HDCht pt. 1 and pt. 2 were in complete remission (CR) and pt. 3 and pt. 4 in partial remission. Pt. 3 converted in CR after HDCht. He is still in CR with a disease-free survival of 23 month after ASTx and 30 month after diagnosis. Pt. 1, 2 and 4 died from relapse 10, 16 and 5 month after ASTx and 16, 22 and 9 month after diagnosis. Pts. with neuroendocrine carcinomas might be suitable candidates for HDCht and ASTx.

Adult↗
PubMed1999

CD44 expression in benign and malignant colorectal polyps.

PURPOSE: This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential. METHODS: Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas-in-adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF-2 for CD44 standard protein, VFF-8 for CD44v5, and VFF-7 for CD44v6. RESULTS: Sixty-three percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninety-three percent of the low-grade adenomas were CD44 standard protein-positive, in contrast to 50 percent of the high-grade adenomas and only 42 percent of the carcinomas-in-adenomas (Kendall's Tau = -0.42; P < 0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high-grade adenomas (25 percent) and low-grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau-b = 0.39; P = 0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high-grade atypia (71 percent), compared with low-grade adenomas (93 percent; Kendall's Tau-b = -0.28; P = 0.004). CONCLUSIONS: Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further.

Adenoma↗
PubMed1998

Restriction digest PCR (RD-PCR) for the analysis of gene mutations. Application to Ki-ras.

The Kirsten-ras (onco)gene codes for a GTP-binding membrane protein that is involved in signal transduction. Activated ras triggers a cascade of protein-phosphorylations that ultimately lead to cell proliferation. Ras-mutations are the main cause for adenocarcinomas of the pancreas besides some mutations in the tumor suppressor gene p53 and the c-erbB-2 oncogene. The site of ras mutations in pancreatic cancer is restricted to codon 12 that normally encodes a glycine. For analysis of codon-12 mutations, DNA is extracted from cells in pancreatic fluid and amplified by PCR. Because most of these cells originate from normal tissue with only a few tumor cells in the fluid, "enrichment PCR" must be utilized: In a first round of the PCR, ras sequences from all cells are amplified. By utilizing an appropriate restriction enzyme, wild-type sequences can be digested and the remaining fragments containing mutated sequences be amplified again. An artificial restriction site must be introduced by the 5'primer (...GGA CCT GGT...) for an enzyme (BstNI) (5'CC!WGG 3') to differentiate between wild-type sequence (...GGA GCT GGT...) (during amplification, the G is replaced by a C) and mutated sequences (_...GGA GCT (GTT), (CGT), (CCT), etc.). The necessary manipulations pose a considerable risk for contamination for the second round of the PCR procedure. Therefore, we considered whether it would be feasible to perform the restriction digest simultaneously with the first PCR reaction, and avoiding the second round altogether. The results of our experiments demonstrate that one tumor cell in 1000 normal cells can be determined readily, paralleling the results with the original two step-assay. The restriction enzyme used to enrich mutated sequences is stable long enough to be included into the PCR procedure. By this, wild-type sequence amplicons are digested while they are formed and mutated sequences can be enriched selectively.

Base Sequence↗
PubMed1996

Detection of common hepatitis C virus subtypes with a third-generation enzyme immunoassay.

The causal agent of most posttransfusion non-A and non-B hepatitis infections was characterized in 1989 by molecular biological techniques as a positive-stranded, enveloped RNA virus, designated hepatitis C virus (HCV). Only since 1990 has it been possible to screen for an infection with antibody tests or direct amplification assays for the nucleic acid (i.e., reverse-transcription polymerase chain reaction [PCR]). However, these nucleic acid based tests are time consuming and rather expensive. Recently, third-generation enzyme immunoassays (EIAs) for HCV infection were introduced (i.e., Abbott Laboratories, North Chicago, IL; Ortho Diagnostics, Inc., Raritan, NJ; and Roche Diagnostics, Basel, Switzerland). The Roche Diagnostics EIA has been evaluated with our patient population. To this end, 1,090 samples were assayed by both EIA and PCR; 946 of all samples (87%) were negative, and 107 samples (9.8%) were positive by both tests. Thirty of the patients (2.7%) showed antibodies but no detectable virus, whereas 7 of all patients tested (0.6%) were PCR-positive but had not yet developed antibodies to the virus. Of these 7 patients, only one showed normal serum transaminases. Virus strain subtyping and quantification of viral load on the positive samples in parallel have been performed, and the fact that the EIA detects all the virus subtypes found in our hospital can be inferred. No correlation between subtypes, viral load, and immune response could be measured with this antibody test. Our results indicate that, in most circumstances (except in settings where immunocompromised patients are abundant), this EIA can replace the much more expensive PCR tests for the routine screening for HCV infection.

Adolescent↗
PubMed1995

Combined intraperitoneal plus intravenous chemotherapy after curative resection for colonic adenocarcinoma.

Patients who underwent potential curative surgery for colonic adenocarcinoma were enrolled in a prospectively randomised, controlled clinical trial of combined intraperitoneal (i.p.) plus systemic intravenous (i.v.) chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant treatment approach, specifically addressing the risk of peritoneal and hepatic recurrence, could improve disease-free and overall survival. Between May 1988 and December 1990, 121 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned for observation (which was considered standard care until the NIH consensus conference) or adjuvant chemotherapy with LV (200 mg/m2) plus 5-FU (350 mg/m2), both given i.v. (days 1-4) and i.p. (days 1 and 3) every 4 weeks for a total of six courses. After a median follow-up time of 4.6 years, a comparative analysis between the two groups of patients suggested both an improvement in disease-free survival (75% versus 58%; P = 0.06) and a survival advantage (78% versus 63%; P = 0.05) in favour of adjuvant chemotherapy. The sites of recurrence were also different, i.e. local regional and intrahepatic tumour recurrences were observed in only 6/58 (10%) and 5/58 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%) observed patients. The overall benefit of adjuvant therapy appeared to be greatest in patients with stage III colon cancer. Treatment-associated toxicity was infrequent and generally mild with only 5% experiencing severe (WHO grade 3) adverse reactions. Interim results of this adjuvant trial suggest that combined i.p. plus systemic i.v. chemotherapy with 5-FU and LV represents a potentially effective adjuvant regimen in stage II/III colon cancer.

Adenocarcinoma↗
PubMed1995

[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna].

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Austria↗
PubMed1995

[Autologous bone marrow transplantation in intestinal carcinoma].

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Bone Marrow Transplantation↗
PubMed1995

[Possible role of autotransplantation in small cel bronchial carcinoma].

Autologous bone marrow transplantation (ABMT) performed with recent achievements plays yet no established role in the treatment of small cell lung cancer (SCLC). The majority of treatment results obtained so far do not clearly suggest a superiority of high-dose therapy with autologous transplantation over conventional polychemo/radiotherapy. It is unknown, whether or not a subgroup of patients with, e.g., "limited disease" and chemosensitive tumor may benefit from ABMT. Randomized trials will be necessary to clarify this question.

Bone Marrow Transplantation↗
PubMed1995

[Electronic data processing-assisted high dosage therapy with stem cell transplantation at the Donauspital].

Organization of high dose chemotherapy with stem cell transplantation essentially requires EDV-support. "ONCOBASE" has been adapted into the Donauspital network on May 1, 1992. We report about the 2-year clinical experience with ONCOBASE: 1. ONCOBASE effectively supports communication between the ward, ambulance and hospital pharmacy (where all cytostatics are prepared). 2. ONCOBASE provides better surveillance concerning all therapeutic procedures including cytostatic drugs and supportive therapies. 3. ONCOBASE allows the generation of medical letters which include all drugs and supportive therapies delivered. 4. Since ONCOBASE is a database program, all informations concerning the patients are registered. These include cumulative drug doses, information on side effects, blood cell kinetics after previous therapies, kinetics of tumor markers and results of further examinations. 5. ONCOBASE permits rapid data exchange with other hospital networks using the communication data record governed by the "Arbeitskreis für EDV der deutschen Gesellschaft für Hämatoonkologie".

Antineoplastic Agents↗
PubMed1994

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.

BACKGROUND: Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression. RESULTS: The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Adult↗