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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 289 records · Page 16Linked to original sources
PubMed1994

High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.

PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.

Adult↗
PubMed1994

Expression of extracellular matrix proteins and the role of fibroblasts and macrophages in repair processes in ischemic porcine myocardium.

In the experimental model of coronary microembolization in pig hearts, the processes of wound healing and scar formation were studied. Methods employed were: electron microscopy, immunohistochemistry using monoclonal antibodies (against fibronectin, laminin, collagen I, III, and VI, chondroitin sulfate, and vimentin), and in situ hybridization with radioactively labeled RNA (histones, fibronectin) or cDNA (acidic fibroblast growth factor) probes. The following time course for expression of various proteins and their mRNAs was established: Mitotic activity was significant at 3 d as well as expression of fibronectin mRNA. Cellularity comprising blood borne cells and macrophages was high. At 7 d, fibronectin, laminin and collagen VI accumulation were pronounced, vimentin positive cells were numerous. At 4 weeks, collagen expression was prominent, but interstitial cells were still present. It is concluded that healing after myocardial necrosis passes through the classical phases of wound healing, i.e., granulation tissue formation and final scar formation. Different extracellular matrix proteins show a differing time course of expression, tumor necrosis factor-alpha (TNF-alpha) and acidic fibroblast growth factor (aFGF) produced by macrophages may be involved in inflammatory processes and angiogenesis. Scar formation is not yet completed at 4 weeks after injury.

Animals↗
PubMed1994

[HLA and transfusion].

Using published data, the role of the HLA system for transfusion of cellular blood components is described. Transfusion-associated immunomodulation and the causative role of HLA in other side effects of transfusion therapy are discussed, using review articles and original papers from the German and English literature as sources. The HLA system has important implications for transfusion therapy. Sensibilization of recipients with consecutive formation of HLA antibodies impairs the support of thrombocytopenic patients and may cause febrile transfusion reactions. HLA antibody formation in donors may result in transfusion-induced acute lung injury. The transfusion of viable lymphocytes may cause graft-versus-host disease in immunocompromised recipients or after directed donations from relatives, in rare cases even without these conditions. The clinical implications of transfusion-associated immunomodulation are judged differently.

Blood Component Transfusion↗
PubMed1994

rHuEPO in the treatment of postpartum anemia: subcutaneous versus intravenous administration.

The aim of this study was to determine whether single-shot therapy with recombinant human erythropoietin (rHuEPO) is as effective as divided dosing in postpartum anemia for both subcutaneous and intravenous administration. In a randomized prospective study we treated 95 women with postpartum anemia (Hb < 10 g/dl) within 72 h after delivery with rHuEPO (total dose 300 U/kg body weight) and oral iron supplementation in four treatment groups: group A rHuEPO 150 U/kg s.c. once daily for two consecutive days; group B rHuEPO 150 U/kg i.v. once daily for two consecutive days; group C rHuEPO 300 U/kg s.c. once only; group D rHuEPO 300 U/kg i.v. once only. No significant intergroup differences were found in the mean increase of hemoglobin (P = 0.93 for a difference of 1 g/dl). The mean increase in the single-shot groups was 3 g/dl in 14 days. There was a significant reduction of iron stores in all groups. We conclude that single-shot rHuEPO 300 U/kg body weight corrects anemia just as effectively as divided doses on both intravenous and subcutaneous administration. The overall increase in Hb is only slight but preliminary results indicate that the effect can be enhanced by administrating iron intravenously and by an interval therapy with high-dose rHuEPO.

Adult↗
PubMed1994

[18 months experience with a new single needle cytapheresis system (Fresenius AS 104 SN)].

BACKGROUND: Since October 1991 the third-generation cell separator Fresenius AS 104 offers a single-needle (SN) option for thrombocytapheresis. Here we present our first 18-month experience with this new single-needle system. MATERIALS AND METHODS: We performed 395 thrombocytaphereses in 225 donors. The influence of blood flow, cycle volume, and interface position on efficacy and leukocyte contamination was evaluated. RESULTS: 395 thrombocytaphereses were performed with an average thrombocyte yield of 3.00 +/- 0.69 x 10(11) platelets and a leukocyte contamination of 1.66 +/- 3.1 x 10(8) per concentrate. Blood flow rates of 50 ml/min (vs. 60 ml/min) and an interface position of 6:2 (vs. 7:1) resulted in a lower leukocyte contamination, but without statistical significance. CONCLUSION: The SN program of the AS 104 provides high thrombocyte yields and less leukocyte contamination than other SN systems, but 77% of the concentrates still contain more than 0.5 x 10(8) leukocytes.

Adult↗
PubMed1994

Tremors in Parkinson's disease: symptom analysis and rating.

The object of the present study was to evaluate the hand tremor occurring under various conditions in 81 patients with Parkinson's disease (PD) and to statistically analyze their relation to clinical rating items. We found that resting and action tremor have to be separated, whereas postural tremor can be related to either one of them. Resting tremor does not correlate with disability items or performance items except for an item rating social handicaps. Action tremor shows some influence on performance items. Current rating scales of PD represent a valid measure of resting tremor but are less valid for the measurement of action tremor.

Adult↗
PubMed1994

Relation between leucocyte depletion and storage.

We intended to answer two questions: (1) Does storage time of platelet concentrates (PCs) influence the efficacy of leucocyte depletion by filtration? (2) Does pre-storage leucocyte depletion by filtration of PCs improve the post-storage quality? To this end we tested in parallel the halves of 10 double-sized PCs, one half stored after filtration through a polyester filter (PL 50, Pall), the other half filtered after a 5-day storage period. Efficacy of leucocyte depletion showed to be independent of the age of PCs, and pre-storage leucocyte depletion of PCs was not able to improve the quality of PCs stored for 5 days, as long as the leucocyte contamination of unfiltered PCs was lower than 0.5 x 10(8)/unit.

Adenosine Diphosphate↗
PubMed1994

Are single-needle protocols equivalent to dual-needle protocols for platelet apheresis?

In light of the increasing demands being placed on cytapheresis donors and their occasional venous problems, it has become necessary to use 1-needle in addition to 2-needle separation techniques in thrombocytapheresis. We therefore compared five 1-needle and three 2-needle programs on four different cell separators and found that meanwhile both the platelet yields and the leukopenia (controlled by Nageotte chamber counting) of the products obtained with the 1-needle technique are equivalent to those obtained using the 2-needle technique, as long as the program is suitably adjusted.

Blood Cell Count↗
PubMed1994

Automated bone marrow concentration using the Fresenius AS 104 blood cell separator.

We concentrated freshly taken bone marrow (BM) pooled from 21 patients from an original 1.265 ml (+/- 537 ml) down to 128 ml (+/- 36 ml) within 40-70 min with a modified version of the 'grancollect protocol' on the Fresenius AS 104 blood-cell separator using the P1-Y set. An average of 47% (+/- 21%) fo the initially present mononuclear cells and 68% (+/- 47%) of the colony-forming cells could be obtained in the concentrate. The erythrocyte concentration was reduced to 7% (+/- 4%) of the original amount. The technique described is very effective and makes is possible to obtain a BM cell population that is suitable for both immunomagnetic purging and cryopreservation or transplantation, e.g. in the case of blood group incompatibility.

Automation↗
PubMed1994

[Various clusters of immunoreactivity in the aged and their relation to HLA antigens and erythrocyte antigens].

In blood samples of members of the Berliner Altersstudie (BASE) (n = 427, 204 males, 223 females; mean = 85.2 years, range = 76-96 years, SD = 3.3 years), red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 12 different mitogens and antigens. Cluster analysis, confirmed by t and F tests, defined 3 distinct clusters of lymphocyte reactivity. Clusters showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens, and trends toward a decreased overall immunoresponsiveness in elder people. Like in middle-aged individuals, immunoresponsiveness in elder individuals can be dissected into at least 3 functionally different clusters which are not influenced by lymphocyte subsets or in vivo cell activation but by the patterns of both red cell and HLA antigens.

Aged↗
PubMed1994

[MLC reactivity demonstrates transfusion-induced immunosuppression].

The improved graft survival in preoperatively transfused renal transplant recipients led to the hypothesis that blood transfusions have an immunosuppressive effect. We examined 12 patients undergoing cardiac surgery, who received autologous red cells and one homologous HLA class-I-matched platelet concentrate. None of these patients produced red cell or lymphocytotoxic antibodies. Using the mixed lymphocyte culture (MLC) we observed a reduced lymphocyte responce to cells of the platelet donor during the first 4 days after transfusion. The MLC reactivity recovered on days 4-5 to the initial strength and reached over 200% of the initial strength from day 6 on. It must be assumed that these changes in MLC reactivity represent the early signs of the transfusion-induced immunosuppression. As intraoperative transfusions might correlate with cancer relapse, further studies must show whether this immunosuppressive effect can be avoided by the application of filtered leucocyte-depleted red cell transfusions.

Blood Transfusion↗
PubMed1994

[Effect of various rabbit complement batches of HLA class I antigen determination in lymphocytotoxicity testing].

HLA class I lymphocytotoxicity testing is strongly complement-dependent. We tested 13 commercially available rabbit complement batches (7 distributors) using a panel of 14 donors with decisive patterns of HLA antigens. We defined a scoring system that weights the different possible faulty reactions. The rating score ranged from 12.45 to 46.55 (median 16.09). Comparing the reactions in batches with low and high rating scores gave statistically significant differences (chi 2 test, p < 0.05). Our complement reaction score may be helpful to find the optimal complement batch for HLA class I lymphocytotoxicity testing.

Animals↗
PubMed1994

[Flow cytometry quality control in stem cell separation].

Peripheral blood-derived haematopoietic stem cells (PBSC) are used as an alternative to bone marrow stem cells for autologous transplantation. One of the most important prerequisites for successful PBSC separation is the precise determination of the optimal separation days. As we previously demonstrated that neither PLT counts nor WBC counts in the peripheral blood (PB) are of predictive value for the amount of colony-forming cells (CFC) in the patients' PB, we started a daily monitoring of CD-34-positive cells to determine the beginning of the separation series. In addition to routine cell counts and CFU testing we assessed the number of CD 34+ in the PBSC concentrates to ascertain the number of separations needed for each patient. Due to the strong correlation of CD 34+ cells to CFC it is possible to predict the number of CFC collected within 2 h after finishing the PBSC separation and to calculate the efficiency of the separation for quality control.

Colony-Forming Units Assay↗
PubMed1994

[Screening for markers of transfusion-associated infections in autologous blood donation].

Autologous blood donation is increasingly used in preparing patients for elective surgical procedures. The aim is to diminish the transmission of transfusion-associated infections, to avoid transfusion-related immunosuppression and to relieve the general blood supply. However, autologous blood donation programs do not necessarily incorporate serologic donor screening. From June 1990 to January 1993 we examined 4,038 consecutive autologous donations from 1,708 patients. The median age was 61 years (range 10-88), the sex ratio was 1/1.5 male/female. We tested each unit for serum ALT, anti-HIV1 + 2, HBsAG, anti-HBc, anti-HCV, and Treponema pallidum antibodies (TPHA test). The overall rates of positive test results were: ALT > 45 U/l 0.64%, anti-HBc 15.9%, BHsAG 0.72% and TPHA test 0.32% of all units; anti-HCV (1st gen.) 4.26% of 1,948 and anti-HCV (2nd gen.) 2.34% of 2,090 donations. With respect to the sex-related normal range of the local laboratory, 332 (8.2%) of all components had an elevated serum ALT level. No donation was positive for anti-HIV1/2. The overall rate of components with pathological findings in tests for ALT, HCV antibodies, HBs antigen and/or Treponema antibodies was 11.7%. We conclude from these data that a substantial proportion of autologous blood is potentially harmful in cases of mistake solely with respect to serologic screening results. Procedures to minimize the risk of mistake of autologous blood should routinely include serologic screening and marking of units with pathological findings.

Adolescent↗