Biomedical subjects

C Wenzel

Publications and source records attributed to C Wenzel.

At least 19 recordsLinked to original sources

PubMed2001

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma.

We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m(2) PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted.

Adult↗

PubMed2001

[Is there progress in chemotherapy for breast cancer?].

Breast cancer is the most frequent type of cancer in women. The therapeutic approaches to breast cancer have developed rapidly over the past 20 years, due to the increasing knowledge about the biology of breast cancer. Therefore it was possible to increase response rates as well as the duration of response and survival in neoadjuvant, adjuvant, and palliative treatment. This paper gives a review of the current breast cancer trials. Effective new cytotoxic chemotherapy and hormonal therapy agents, as well as the identification of specific molecular abnormalities (HER2/neu) led to the development of targeted therapeutic interventions in the neoadjuvant, adjuvant, and palliative treatment of breast cancer. Increased understanding of the biology of breast cancer led to the development of rational therapeutic interventions, which are currently under active clinical development.

Algorithms↗

PubMed2001

Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial.

PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.

Adolescent↗

PubMed2001

Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer patients.

Gemcitabine is a chemotherapeutic agent with proven antitumor effects in pancreatic and non-small cell lung cancer; however, studies establishing the definite significance in other solid tumors are still in progress. We herein present three female patients with advanced breast cancer who received gemcitabine as salvage chemotherapy. Gemcitabine at a dose of 1250 mg/m2 was scheduled for days 1, 8 and 15 with a subsequent rest for 1 week. However, within 1 week after the very first administration of gemcitabine myelotoxicity WHO grade IV occurred in all patients, leading to discontinuation of therapy. In two patients this gemcitabine-induced hematotoxicity could be overcome by means of vigorous supportive care, but one patient died after cerebral bleeding due to severe thrombocytopenia. We conclude that gemcitabine in heavily pretreated breast cancer patients should only be used with extreme caution with special focus on platelet counts until solid data from clinical studies for doses and schedules are available.

Adult↗

PubMed2001

Relapse prevention in reflux oesophagitis with regard to Helicobacter pylori status: a double-blind, randomized, multicentre trial to compare the efficacy of pantoprazole versus ranitidine.

OBJECTIVE: To compare prospectively the effectiveness of 1 year's treatment with pantoprazole versus ranitidine in order to prevent relapse after initial cure of reflux oesophagitis. For the first time the influence of the initial Helicobacter pylori status on therapeutic results was also taken into account. METHODS: In order to cure reflux oesophagitis, 396 patients with Savary/Miller stage II or III reflux oesophagitis were treated with pantoprazole 40 mg once daily for 8 weeks. Those who were H. pylori positive (n = 140) were also given 1 week of eradication treatment with clarithromycin 2 x 250 mg daily, metronidazole 2 x 400 mg daily, and a further 40 mg pantoprazole daily. The 303 patients who were endoscopically cured after the 8-week period were randomized and treated with either pantoprazole 20 mg (n = 199) or ranitidine 150 mg (n = 104) daily in double-blind fashion. The primary objective was to assess the time to endoscopically proven recurrence of reflux oesophagitis. RESULTS: In the intention-to-treat (ITT) population, 66.3% (118/178) of the pantoprazole group and 34.0% (32/94) of the ranitidine group showed neither endoscopic nor clinical symptoms of relapse after the 1-year treatment period (P < 0.0001) (per-protocol populations: 70.3% [109/155] in the pantoprazole group and 39.4% [28/71] in the ranitidine group). In the pantoprazole group, the relapse rate in initially H. pylori-positive patients who underwent eradication was 30.9% (17/55) and in H. pylori-negative patients 29% (29/100). CONCLUSIONS: Long-term treatment with 20 mg pantoprazole daily to prevent relapse of reflux oesophagitis in H. pylori-negative patients is significantly more effective than 150 mg ranitidine daily. The initial H. pylori eradication treatment does not influence the outcome of the long-term treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

CD5 expression in a lymphoma of the mucosa-associated lymphoid tissue (MALT)-type as a marker for early dissemination and aggressive clinical behaviour.

Mucosa associated lymphoid tissue (MALT) developing in response to chronic infection or autoimmune stimuli has been recognized as a possible site of origin for a distinct type of B-cell lymphoma. While preferentially occurring in the stomach, MALT-type lymphomas can be found in virtually all organs. MALT-type lymphomas normally follow an indolent course, with a tendency to remain localized at their site of origin for a prolonged period of time. Histologically, MALT-type lymphomas are heterogeneous covering a cytological spectrum ranging from centrocyte-like cells to smaller lymphoid cells or monocytoid B-cells. Usually a small number of transformed blasts are also present. Immunohistochemically, the malignant cells express markers of B-cell lineage, but are distinct from follicular lymphomas (which express CD10), mantle cell lymphomas (expressing cyclin D1 and CD5) and small lymphocytic lymphoma, which express CD5 and CD23. In contrast to the usual phenotype CD20+CD10-CD5-Cyclin D1-, scattered reports in the literature have documented expression of CD5 in marginal zone B-cell lymphomas of MALT-type. However, these cases are rare, and aberrant CD5-expression has been thought to be a marker for early dissemination and aggressive behavior in some patients, while other reports have also found CD5 expression in localized indolent MALT-type lymphomas. We report a patient with a CD5+ MALT-type lymphoma following an aggressive clinical course without histological progression who relapsed only 18 months after local radiotherapy at the initial localizations (conjunctiva of the right upper eye lid and hypopharynx), and showed a rapid generalization to the contralateral conjunctiva, mediastinal lymph nodes and the esophagogastric junction. Our case lends further support to the notion that CD5+ MALT-lymphomas arising in the head-and-neck area and/or the ocular adnexa might be characterised by an aggressive clinical course.

Aged↗

PubMed2001

[Automatic milking from a behavioral and welfare viewpoint].

Automatic milking systems have been shown to change the behaviour of cows. Because pre-determined milking and feeding times are eliminated, the cows must establish their own daily routine. They have to adapt to being milked according to their lactation. There are, however, indications that not all cows adapt well to the automatic system. Some herd members seem to have inhibitions about entering the milking stall. Too many cows per milking stall and a blocked milking system intensify the situation. Therefore, the cows must either be forced or attracted by food to enter the milking stall. Altogether some cows appear to be more stressed. Furthermore, the human-animal relationship changes due to the new work content. There is less manual work, more observation, and more computer data. The farmer needs to be well educated and must establish a new management program. If care is insufficient, if some herd members are less frequently milked, and if measures to reduce stress are not taken, it is clear that welfare problems could arise. Compared to milk quality and milk hygiene, technical solutions and regulations by law are not as important. Ethological knowledge must be taken into account if automatic milking is to be advantageous for both cow and man.

Adaptation, Physiological↗

PubMed2000

Barriers in cancer pain management.

Inadequate pain management of cancer patients remains a striking problem despite impressive scientific progress in the knowledge of the pathophysiology, pathogenesis and therapy of pain. Our paper focuses on three topics: 1. physician-related barriers, 2. patient-related barriers, and 3. society- and tradition-related barriers as well as government regulations. It is imperative to overcome these barriers, especially since legal regulations for pain management were embodied into statutory regulations in Austria two years ago.

Analgesics, Opioid↗

PubMed2000

Glutathione in the prevention of cisplatin induced toxicities. A prospectively randomized pilot trial in patients with head and neck cancer and non small cell lung cancer.

PURPOSE: Glutathione has been shown to be an effective chemoprotector against cisplatin-induced side effects in patients with ovarian cancer. In view of this fact, we performed a randomized clinical pilot-trial in the management of other solid tumors in order to compare application of Glutathione to intensive hydration in patients undergoing chemotherapy with a regimen including cisplatin. PATIENTS AND METHODS: Twenty patients suffering from advanced non small cell lung cancer (n = 6) or head- and neck cancer (n = 14) were enrolled in the study. All patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every 4 weeks. Patients randomized to application of Glutathione (n = 11) received 5 g of Glutathione immediately before application of cisplatin followed by 2000 ml of normal saline. Patients in the control group (n = 9) received 2000 ml electrolyte infusion before and 2000 ml of normal saline with forced diuresis after cisplatin. RESULTS: The intensity of hematologic toxicity was significantly less pronounced in patients treated with Glutathione than in the control group (hemoglobin: 10.7 vs 9.5 mg% respectively, p = 0.039; white blood cell count 3.3 vs 2.2 x 103/microliter respectively, p = 0.004; platelets 167 vs 95 x 103/microliter respectively, p = 0.02), whereas in terms of non-hematologic toxicity no difference was observed. Objective remission occurred in 6 out of 11 evaluable patients from the group receiving Glutathione (55%; complete remission: 9%; partial remission: 46%), and in 4 out of 8 evaluable patients from the control group (partial remission: 50%). However, there was no statistical difference in terms of response and overall survival (13.5 months vs. 10.5 months) between the two groups. CONCLUSIONS: Application of Cisplatin and Glutathione seems to be safe and feasible and the antitumoral efficacy of cisplatin is apparently not impaired by the concomitant use of Glutathione in patients with solid tumors.

Adult↗

PubMed2000

[Pain management in view of current new legislative updates and their practical consequences in Austria].

Although the WHO edited guidelines for pain treatment as early as 1986, practical management has frequently remained inadequate, especially in cancer patients. Traditional adherence to restrictions from the former Austrian Controlled Drug Act which have resulted in ongoing limitations in the prescription of opioids as well as complicated formal regulations in the current law represent two major obstacles. As a consequence, recent legislation of a "state of the art" pain management in Austria facilitates adequate provision of analgesics on the one hand, and may, on the other, even result in claims for indemnity should these be withhold.

Analgesics, Opioid↗

PubMed2000

Sequential administration of interferon gamma and interleukin-2 in metastatic renal cell carcinoma: results of a phase II trial. Austrian Renal Cell Carcinoma Study Group.

BACKGROUND: Because of the known efficacy of several cytokines in the treatment of advanced renal cell cancer (RCC), we have conducted a phase II trial of the efficacy and toxicity of subcutaneous interferon gamma (IFNgamma) and interleukin-2 (IL-2). METHODS: 63 patients with progressive metastatic RCC were treated with 100 microg recombinant IFNgamma1b administered three times weekly during weeks 1 and 2 and with 4.5 MU recombinant IL-2 administered on 4 consecutive days during weeks 3 and 4, every 6 weeks. RESULTS: 11% of patients had an objective response (CR: 3%, PR: 8%), 33% had SD. Toxicity was generally mild. The median duration of remissions (CR + PR) was 9.6 months; the median duration of SD 8 months. A significant survival benefit was evident at a median observation time of 51 months for patients (44%) responding to therapy (P < 0.0001). CONCLUSIONS: we conclude that sequential treatment with IFNgamma and IL-2 may prolong survival in patients with metastatic RCC responding to therapy.

Adult↗

PubMed2000

Karyotypic findings in two cases of male breast cancer.

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.

Aged↗

PubMed2000

Vinorelbine and interferon-alpha2c as second-line therapy in metastatic renal cell carcinoma.

Second-line treatment of patients with metastatic renal cell carcinoma (MRCC) progressing under therapy with biological response modifiers (BRM) is an unresolved issue. Thirty-seven patients with MRCC progressing under treatment with BRM received vinorelbine i.v. at a dose of 30 mg/m2 q 22 days and 4,800,000 IU interferon (IFN)-alpha2c s.c. thrice weekly. Partial remission (PR) occurred in 8% of patients, stable disease (SD) (median duration 8, range 3-35+ months) was observed in 46% of patients. Median overall survival was 15 (range 1-49) months. No major toxicities occurred. Patients with MRCC who failed first-line treatment with BRM had a high chance to enter PR or SD under combined, low-toxic therapy with vinorelbine and IFN-alpha2c.

Adult↗

PubMed2000

Decrease of circulating hematopoietic progenitor cells During interleukin-2 treatment is associated with an increase of vascular cell adhesion molecule-1, a critical molecule for progenitor cell adhesion.

Administration of interleukin-2 (IL-2) to cancer patients has been shown to transiently decrease the number of circulating hematopoietic progenitor cells, but the mechanism of this phenomenon is unknown. Recently, the interaction of vascular adhesion molecule-1 (VCAM-1) with leukocyte very late antigen-4 (VLA-4) has been demonstrated to play a crucial role in the adhesion of progenitor cells to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to increased binding of progenitor cells to stromal cells in vitro, and inhibition of this interaction by monoclonal antibodies is associated with marked progenitor cell mobilisation in vivo. In the present study we serially determined peripheral blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer patients and determined in parallel levels of soluble VCAM-1 as a surrogate marker for the in vivo activation of this molecule. Our data indicate that continuous intravenous administration of IL-2 for 5 days leads to a marked decrease of circulating progenitor cells associated with a substantial increase of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from a mean value of 167 +/- 187 / ml pre IL-2 to 16 +/- 15 / ml on day 3 (p < 0.01). Similarily, mean erythroid progenitors (BFU-E) decreased from 282 +/- 204 / ml before IL-2 administration to 86 +/- 61 / ml on day 3 (p < 0.005). In contrast, soluble VCAM-1 rose from a mean value of 1814 +/- 451 ng/ml before to 4607 +/- 736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated patients did not inhibit hematopoietic colony formation from normal bone marrow. These results suggest redistribution and increased adhesion of progenitor cells to stromal and/or endothelial elements during IL-2 via the VCAM-1/VLA-4 interaction as a possible mechanism for the decrease of circulating progenitor cells during IL-2 therapy.

Adult↗

PubMed2000

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Adult↗

PubMed1999

[Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1-4, N0-2, M0)].

BACKGROUND: Preoperative (neo-adjuvant) chemotherapy is very effective in downstaging primary tumors and moreover is able to prevent advancing metastatic growth early in the course of the disease. METHODS: We report on 38 patients with a median age of 54 years (range, 33-70 years) suffering from biopsy-proven breast cancer (T1-T4). Mastectomy had been considered the treatment of choice in all cases. The patients received 194 cycles of chemotherapy with docetaxel (75 mg/m2) and epidoxorubicin (75 mg/m2) on day 1, every 21 days, together with 30 million IU of G-CSF from days 3 to 10. Three to 8 cycles (median 5 cycles) of the treatment were administered until best response was achieved on mammography and clinical assessment. RESULTS: The neo-adjuvant chemotherapy was well tolerated and all patients completed the treatment regimen on an out-patient basis. During 194 cycles we observed leukopenia WHO grade IV only at one occasion (0.5%). WHO-grade III toxicity consisted of leukopenia (0.5%), diarrhoea (2%), and stomatitis (0.5%). Response to treatment was present in 85%, with 4 patients (11%) experiencing a pathological complete response (pCR) of the invasive tumor (T0: n = 2, DCIS: n = 2) and 28 patients (74%) showing a partial pathological response. In 21 patients (52%) a breast-conserving surgical procedure was possible. SUMMARY: We conclude that neo-adjuvant treatment of primary breast cancer with docetaxel and epidoxorubicin is safe and effective. By applying more chemotherapy cycles preoperatively it might even be possible to raise the rate of pCR and prolong survival.

Adult↗

PubMed1998

Clinical outcome at six months of coronary stenting followed by ticlopidine monotherapy.

Antiplatelet therapy has been shown to be superior to oral anticoagulation after coronary stent implantation. Different regimens for postinterventional antiplatelet therapy have been proposed. A combination of ticlopidine and aspirin has gained the most widespread use. The relative merit of the different compounds in this combination remains unclear. There are several, partly conflicting, reports on coronary stent implantation followed by aspirin alone, but data on ticlopidine monotherapy are scarce. We conducted a prospective trial of elective coronary stenting followed by ticlopidine monotherapy in 263 consecutive, unselected patients. One-, 2-, and 3-vessel disease was present in 42.9%, 42.6%, and 14.5% of patients, respectively. We deployed a total of 322 stents. All patients received 250 mg of ticlopidine twice daily for up to 6 months. The clinical end points encountered during the hospital stay and at 5.9+/-2.9 months, respectively, were: death (2 [0.8%] and 2 [0.8%]); myocardial infarction (5 [1.9%] and 4 [1.5%]); target vessel occlusion (2 [0.8%] and 4 [1.5%]); bypass surgery (0 and 2 [0.8%]); and repeat angioplasty (2 [0.8%] and 52 [19.8%]). There was 1 vascular surgery (0.4%) and 4 (1.5%) non-procedure-related ischemic cerebrovascular events at follow-up. We conclude that coronary stent deployment followed by ticlopidine monotherapy is safe and effective in an unselected population. The overall clinical outcome at 6 months is good and comparable to that of patients treated with combined antiplatelet therapy. Ticlopidine monotherapy may be a safe alternative for patients with contraindications to aspirin.

Adult↗