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Biomedical subjects

G Krieger

Publications and source records attributed to G Krieger.

At least 19 recordsLinked to original sources

Ondansetron is no more effective than supplemental intraoperative oxygen for prevention of postoperative nausea and vomiting.

UNLABELLED: Supplemental oxygen maintained during and for 2 h after colon resection halves the incidence of nausea and vomiting. Whether supplemental oxygen restricted to the intraoperative period is sufficient remains unknown. Similarly, the relative efficacy of supplemental oxygen and ondansetron is unknown. We tested the hypothesis that intraoperative supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Patients (n = 240) undergoing gynecological laparoscopy were given a standardized isoflurane anesthetic. After induction, they were randomly assigned to the following three groups: routine oxygen administration with 30% oxygen, balance nitrogen (30% Oxygen group), supplemental oxygen administration with 80% oxygen, balance nitrogen (80% Oxygen group), and Ondansetron 8 mg (immediately after induction), combined with 30% oxygen, balance nitrogen (Ondansetron group). The overall incidence of nausea and/or vomiting during the initial 24 postoperative h was 44% in the patients assigned to 30% oxygen and 30% in the Ondansetron group, but only 22% in those given 80% oxygen. The incidence was thus halved by supplemental oxygen and was significantly less than with 30% oxygen. There were, however, no significant differences between the 30% oxygen and ondansetron groups, or between the ondansetron and 80% oxygen groups. We conclude that supplemental oxygen effectively prevents postoperative nausea and vomiting after gynecological laparoscopic surgery; furthermore, ondansetron is no more effective than supplemental oxygen. IMPLICATIONS: Supplemental oxygen reduces the risk of postoperative nausea and vomiting (PONV) as well or better than 8 mg of ondansetron. Because oxygen is inexpensive and essentially risk-free, supplemental oxygen is a preferable method of reducing PONV.

Adult↗

[Long-term results with MACOP-B and radiation therapy for aggressive lymphomas].

BACKGROUND: Long-term results are needed to evaluate chemotherapy regimens and prognostic factors in non-Hodgkin's lymphomas (NHL). We report the 10-year follow-up data of aggressive NHL classified according to the Kiel classification and treated with MACOP-B. PATIENTS AND METHODS: Between 1985 and 1991, 71 patients with aggressive NHL were treated in a single institution with MACOP-B and adjuvant radiotherapy as first-line therapy. NHL subtypes were classified according to the updated Kiel classification. Follow-up data were available until 1998. RESULTS: The overall survival (OS) at 10 years is 45% (confidence interval 33-57%), the progression-free survival 42% (30-54%), and the relapse-free survival of the 59 patients (82%) in complete remission is 52% (39-65%). The Kiel classification combined with the International Prognostic Index (IPI) identified diffuse large B-cell and anaplastic large T-cell lymphomas with IPI 0-2 as subgroups with very favorable prognosis after MACOP-B (OS 84% and 80% at 10 years). Late relapses (>2 years after therapy) did occur in these patients but had a good prognosis after second remission. Only 3 of 24 relapses were in the radiation field. Three patients died of toxicity, 1 during MACOP-B (1.3%). Risk factors for therapy-related death were age and pulmonary toxicity. Most patients suffered from chemotherapy-associated mucositis. Osteoporosis was a common late toxicity (39%). Three second cancers but no leukemias or myelodysplastic syndromes were observed during follow-up. CONCLUSIONS: MACOP-B in combination with adjuvant radiotherapy is highly effective in diffuse large B-cell or anaplastic large T-cell-lymphomas with IPI 0-2. Patients with IPI >2 or with centrocytic or secondary centroblastic B-cell or non-anaplastic T-cell lymphomas need more intensive therapy or novel approaches. Regarding the toxicity profile, MACOP-B should be replaced by VACOP-B.

Adult↗

Object and scene analysis by saccadic eye-movements: an investigation with higher-order statistics.

Based on an information theoretical approach, we investigate feature selection processes in saccadic object and scene analysis. Saccadic eye movements of human observers are recorded for a variety of natural and artificial test images. These experimental data are used for a statistical evaluation of the fixated image regions. Analysis of second-order statistics indicates that regions with higher spatial variance have a higher probability to be fixated, but no significant differences beyond these variance effects could be found at the level of power spectra. By contrast, an investigation with higher-order statistics, as reflected in the bispectral density, yielded clear structural differences between the image regions selected by saccadic eye movements as opposed to regions selected by a random process. These results indicate that nonredundant, intrinsically two-dimensional image features like curved lines and edges, occlusions, isolated spots, etc. play an important role in the saccadic selection process which must be integrated with top-down knowledge to fully predict object and scene analysis by human observers.

Adult↗

Synergistic DNA damaging effects of malondialdehyde/Cu(II) in PM2 DNA and in human fibroblasts.

Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In combination with CuCl2 MDA induced single strand breaks in PM2 DNA whereas MDA or CuCl2 alone had no effect. Cu(II) oxidized MDA by a radical mechanism under formation of Cu(I). DNA strand break induction was inhibited by catalase (98%), neocuproine (76%) and DMSO (61%). The synergistic damaging effect of MDA and Cu(II) was also demonstrated in human fibroblasts measured by alkaline elution. The combination MDA/CuCl2 caused extensive DNA breakage while neither MDA nor CuCl2 alone induced DNA damage within the cell. Synergistic cytotoxic effects were observed 18 h after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h.

Administration, Topical↗

Different DNA damaging species as a result of oxidation of n-butyraldehyde and iso-butyraldehyde by Cu(II).

The isomers n- and iso-butyraldehyde (BuA) in combination with Cu(II) induced single and double strand breaks in PM2 DNA, whereas the aldehydes, or Cu(II) alone had only negligible effect. The DNA damage was the result of radical oxidations of the aldehydes under formation of Cu(I). Cu(I) formation was independent of molecular oxygen. Extensive DNA degradation was only observed in the presence of molecular oxygen. Characterization of DNA damage pointed to different ultimate DNA damaging species. While catalase and neocuproine inhibited strand break formation induced by iso-BuA/Cu(II) to a high degree, these inhibitors were less effective in the n-BuA/Cu(II) reaction. On the other hand, sodium azide showed a high strand break inhibition in the n-BuA/Cu(II) reaction, but low inhibition in the iso-BuA/Cu(II) reaction. 2-Deoxyguanosine was hydroxylated in the 8-position by iso-BuA/Cu(II) but little reaction occurred with n-BuA/Cu(II). Chemiluminescence was detected during both BuA/Cu(II) reactions, whereby the intensity of the luminescence signal was 3.5-fold higher for n-BuA/Cu(II) than for iso-BuA/Cu(II). We suppose that the copper(II)-driven oxidation of n- and iso-BuA proceeds via different pathways with different DNA damaging consequences. Whereas the oxidation of iso-BuA mainly results in damage by .OH-radicals, the oxidation of n-BuA may lead to a radical reaction chain whereby excited states are involved and the resulting DNA-damaging species are not .OH-radicals.

8-Hydroxy-2'-Deoxyguanosine↗

Neural network models and the visual cortex: the missing link between orientation selectivity and the natural environment.

Orientation selectivity is a basic property of neurones in the visual cortex of higher vertebrates. Such neurones can be seen to act as 'feature detectors', which provide an efficient cortical representation of the outside world. More recently, the removal of correlations between the signals of cortical neurones has been suggested as suitable theoretical concept for explaining the development of receptive fields. Corresponding neural network simulations yielded oriented 'receptive field' structures resembling those observed by neurophysiologists. The findings suggest that the 'decorrelation approach' can provide a causal relationship between characteristics of the physical world and brain function. However, we were able to reveal a basic deficit of the decorrelation approach which we illustrate by the construction of two artificial 'worlds', a 'Gaussian' one and an 'orientation-only' one. We show that, according to the decorrelation approach, oriented environmental features would be neither necessary nor sufficient for the development of oriented receptive fields. Thus the link between environmental structure and cortical orientation selectivity still awaits a theoretical explanation.

Environment↗

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for metastatic gastric leiomyosarcoma.

We report a case of metastatic gastrointestinal leiomyosarcoma treated with high-dose combination chemotherapy and autologous peripheral blood stem cell transplantation. After incomplete surgical resection, enteral, peritoneal and hepatic involvement remained. Postoperatively, standard-dose chemotherapy with etoposide, ifosfamide, cisplatin and epirubicine, and high-dose chemotherapy with the same agents (carboplatin replacing cisplatin) was given. Treatment was well tolerated and the patient remains in complete remission at 36+ months. We conclude that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation may be of use as treatment for inoperable residual disease after resection of the primary lesion in gastrointestinal and other soft tissue sarcomas.

Adult↗

The IPRS Image Processing and Pattern Recognition System.

IPRS is a freely available software system which consists of about 250 library functions in C, and a set of application programs. It is designed to run under UNIX and comes with full source code, system manual pages, and a comprehensive user's and programmer's guide. It is intended for use by researchers in human vision, pattern recognition, image processing, machine vision and machine learning.

Humans↗

DNA single and double strand breaks induced by aliphatic and aromatic aldehydes in combination with copper (II).

The aliphatic n-butyr-and n-valeraldehyde as well as the aromatic benz- and anisaldehyde induced DNA strand breaks in PM2 DNA in the presence of CuCl2. Neither aldehydes nor CuCl2 alone showed DNA breakage properties. The maximum of single strand breaks (SSBs) induced by the combination of CuCl2 and aldehydes was dependent on the CuCl2-concentration. The aliphatic aldehydes induced SSBs and double strand breaks (DSBs) at lower concentrations than aromatic aldehydes when optimal CuCl2 concentration were used. Catalase and neocuproine nearly completely inhibited strand break formation induced by aromatic aldehydes/CuCl2. The prevention of strand breaks induced by aliphatic aldehydes/CuCl2 was less effective. While the inhibition by neocuproine was only 25%, catalase was totally ineffective. In all aldehydes/CuCl2 mixtures the formation of Cu(I) was observed. The results point to different DNA damaging species produced during redox reactions of aromatic and aliphatic aldehydes in combination with CuCl2.

Aldehydes↗

Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers.

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Diagnostic and intensive care problems in hemolytic uremic syndrome].

We observed a young man with apparently septic appendicitis who finally could be diagnosed as suffering from haemolytic uraemic syndrome (HUS) when spuriously normalising platelet counts were identified as a cell counter artifact. This case stresses the fact that automatically counted abnormal thrombocyte numbers should be examined by microscopy. Therapy is empirically based on corticosteroids, plasmapheresis and fresh frozen plasma. The application of thrombocyte concentrates should be avoided because of the risk of aggravating the disease process.

Adult↗

Binding of fluorescein-labeled anaphylatoxin C5a to human peripheral blood, spleen, and bone marrow leukocytes.

The expression of C5a receptors (C5aR) on human leukocytes was evaluated by flow cytometry using fluorescein-labeled human C5a (C5a-F). Granulocytes and CD14+ mononuclear cells (MNL) but not CD3+, CD20+, CD16+, CD56+, or CD11b+ lymphocytes in peripheral blood and spleen bound C5a-F. C5a-F binding was saturable and inhibitable by anti-C5a monoclonal antibody (MoAb) C17/5 or unlabeled C5a. During hemodialysis, which led to the generation of C5a, only granulocytes and monocytes increased their expression of the adhesion molecule CD11b (CR3). In vitro, C5a induced an increase of CR3 and p 150/95 (CD11c/CR4) only on myeloid cells. However, treatment of leukocytes with phorbol 12-myristate 13 acetate increased CR3 and CR4 expression on both myeloid cells and a lymphocyte subpopulation. Stimulation of MNL in mixed lymphocyte cultures or by treatment with conditioned medium or with IFN-gamma did not induce binding sites for C5aR on lymphocytes and reduced the binding of C5a-F to monocytes. The expression of C5aR on low-density bone marrow cells was analyzed by setting appropriate gates during flow cytometry. Cells that bound C5a-F were found in all populations that contained granulocyte and monocyte precursors, but not in lymphocyte precursor populations. All C5aR+ bone marrow cells were CD34 and expressed high levels of CR3, which suggests a late appearance of C5aR during myeloid cell maturation. Our results indicate that C5aR is exclusively expressed on myeloid cells within the hematopoetic cell population.

Antibodies, Monoclonal↗

The growth capacity of hematopoietic progenitor cells in severe neutropenia induced by famotidine.

In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3-(IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7-17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10 micrograms/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150 micrograms/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1-5.0 micron/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process.

Adult↗