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Biomedical subjects

R Naumann

Publications and source records attributed to R Naumann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Foscarnet--an alternative for cytomegalovirus prophylaxis after allogeneic stem cell transplantation?

Cytomegalovirus (CMV) disease is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with high morbidity and mortality. Early detection of the disease by antigenemia testing and polymerase chain reaction (PCR) along with pre-emptive antiviral therapy has been shown to be very effective in decreasing the incidence of CMV. We performed an uncontrolled observational study in 21 patients after HSCT (14 related, 7 unrelated donors) to evaluate the efficacy and toxicity of foscarnet administered as prophylaxis for CMV reactivation. Ten patients received bone marrow, and eleven patients received peripheral blood stem cells. All patients received foscarnet prophylaxis to study side effects, incidence of CMV reactivation, CMV disease, and transplant-related mortality. Foscarnet (90 mg/kg) was given every 12 h, day +11 to day +16. Thereafter, foscarnet (90 mg/kg) was given once per day, three times per week until day +60. The incidence of CMV reactivation detected by antigenemia (pp65 antigen) or PCR was 23.8% (5 of 21 patients). Two patients developed CMV disease and one patient died of CMV-pneumonia. Seventeen patients (81%) reported severe side effects, such as gastrointestinal disturbance, headache, and urethritis. In eight patients (38%), the dose of foscarnet had to be reduced and, in six patients (28.5%), foscarnet application was discontinued because of side effects. Compared with other groups, we believe that the potential benefit of foscarnet administration in this early setting is outweighed by the risks of severe toxicity.

Adult↗
PubMed2000

Functional tethered lipid bilayers.

Our strategy to provide the structural basis for the build-up of functional tethered membranes focuses on three approaches: the first one is based on the pre-organization of a monomolecular layer of a lipopolymer at the water/air interface which is then transferred to a solid support. Prior to deposition, the substrate is coated with a layer of benzophenone-derivatized silane molecules that allow for a stable covalent attachment by photo-cross-linking of some of the monomer units of the lipopolymer to the support. An alternative concept realizes a layer-by-layer deposition of the various structural elements: (1) the attachment layer with the reactive sites for the chemical stabilization; (2) a polymer 'cushion' prepared by adsorption and simultaneous or subsequent partial covalent binding to the reactive sites; and (3) a lipid monolayer transferred from the water/air interface, that contains a certain amount of lipids with reactive headgroups which, upon binding to the polymer tether, act as anchor lipids stabilizing the whole monolayer/cushion-composite. And finally, we build peptide-supported monolayers by first (self-) assembling amino acid sequences of various lengths via a SH-group near their N-terminus onto Au substances and use then their COO(-)-terminus to chemically attach phosphatidyl-ethanolamine lipids to form a stable monolayer of lipid-peptide conjugates. All the individual preparation steps and the various resulting (multi-) layers are characterized by surface plasmon spectroscopy, X-ray and neutron-reflectometry, contact angle measurements, IR spectroscopy, fluorescence microscopy, scanning probe microscopies, as well as, electrochemical techniques. For all tethering systems, the final membranes' architecture is obtained by fusing lipid vesicles onto the lipid monolayer. Proteins can be incorporated by either fusing vesicles that are loaded with the respective receptors, pores, or ion pumps via a reconstitution procedure, or via a transfer directly from a micellar solution to the pre-formed lipid bilayer at the solid support by a dialysis step. Two structural/dynamical features of tethered membranes which are considered to be of particular functional relevance, i.e. the degree of water uptake and, hence, the degree of swelling of the polymer support, as well as the lateral mobility of the lipid molecules in the membrane, are tested by surface plasmon optics and by measurements of the fluorescence recovery after photobleaching (FRAP), respectively. The results confirm that the presented preparation protocols yield fluid bilayers that mimic certain relevant properties of biological membranes. The functional characterization of tethered membranes, which is briefly summarized, is based on various electrochemical techniques, in particular, impedance spectroscopy, cyclic voltammetry, and chronoamperometric studies. The results obtained for reconstituted H(+)-ATPase from chloroplasts and E. coli and for cytochrome oxidase (with and without cytochrome c) confirm the incorporation of the proteins in an active form, thus, opening opportunities for novel sensor formats or offering a completely new model membrane system.

Biopolymers↗
PubMed2000

Encouraging results in the treatment of haemorrhagic cystitis with estrogen - report of 10 cases and review of the literature.

Haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (HSCT) or high-dose cyclophosphamide (CP) chemotherapy is a severe side-effect and can cause significant morbidity and mortality. In this report, we describe the clinical courses of 10 patients with HC and review the literature. The patients were treated with oral conjugated estrogen in an attempt to improve severe haemorrhagic cystitis. In seven patients positive effects were seen, haematuria resolved in all, but residual symptoms of dysuria remained for longer periods. In one patient application of estrogen was interrupted because of hepatotoxicity. Two patients failed all treatment modalities including oral estrogen because of terminal illness. We conclude that in the management of HC the administration of oral conjugated estrogen should be considered.

Administration, Oral↗
PubMed2000

Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin.

Between February 1998 and October 1999, 24 patients with advanced leukemia, lymphoma or solid tumors received G-CSF mobilized peripheral blood stem cells (PBSC) from HLA-matched sibling donors after dose-reduced conditioning therapy. Only patients with reduced performance status or major infectious complications, not eligible for standard transplant procedures, were included. The 5-day conditioning therapy consisted of 3.3 mg/kg intravenous busulphan x 2 days and 30 mg/m2 fludarabine x 5 days. GVHD prophylaxis was performed with either CsA alone (n = 5), CsA combined with short course methotrexate (n = 5) or mycophenolate mofetil (n = 14). The day 100 survival was 95.2% for the whole group. All patients engrafted after a median of 15 days (range, 11-19) and 12.5 days (range, 10-19) for neutrophils and platelets, respectively. The median time to a neutrophil count of <0.5 x 109/l was 7 days (range, 2 to 12). Acute GVHD >I was observed in six patients, whereas eight patients have signs of chronic GVHD. The prospective 12 month overall survival with a median follow-up of 7 months is 63%. Relapse of disease and toxicity associated with chronic GVHD were the main causes of death. The treatment-related mortality was 12.5%. Dose-reduced conditioning using intravenous busulphan and fludarabine allows stable engraftment without ATG in related transplants and leads to a reduction of transplant-related mortality.

Adult↗
PubMed1999

Olanzapine-induced agranulocytosis.

The antipsychotic drug olanzapine was developed to reduce the risk of haematotoxicity. We report a case of agranulocytosis induced by olanzapine.

Adult↗
PubMed1999

Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocytes. Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We performed a pilot study evaluating the feasibility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailability of MMF in this setting were investigated. METHODS: Fourteen patients who had received grafts from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined with intravenous CsA at 4 mg/kg starting at day-1. Plasma levels of mycophenolic acid (MPA) and its glucoronide were measured by high-performance liquid chromatography. Fifteen patients treated with a combination of CsA and methotrexate at the same institution were referred to as the control group. RESULTS: Trilineage engraftment was achieved in all study and control patients. Acute GVHD > or = grade II was observed in 46.5% and 60% of the study and control patients, respectively. No major differences in the rate of acute toxicities were detectable. The mean trough blood level of MPA in 10 patients was 0.28 microg/ml, and 5.7 microg/ml for MPA glucoronide. Reduced peak levels of MPA indicate a reduced absorption rate of MMF in the early posttransplant phase. CONCLUSIONS: The combined administration of MMF and CsA was shown to be feasible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intravenous formulation are warranted.

Adult↗
PubMed1999

[Candidiasis in cancer patients: Epidemiology, diagnosis, prophylaxis and therapy].

New approaches in successful treatment of cancer patients are impaired by increasing incidence of fungal infections with high mortality. Relevant prognostic factors could be identified by numerous trials, such as age, kind and status of disease, intensity of previous chemotherapy, bone marrow transplantation, advanced fungal colonization of gastrointestinal tract. In clinical practice options for prompt and sensitive diagnostics are limited despite of new PCR-techniques. Prophylactic efficiency of polyenes or azoles is proven in high risk patients. Amphotericin B is established for treatment in case of documented or assumed invasive fungal infection. Liposomal preparations are less toxic and at least as effective as conventional amphotericin B in randomized trials.

Amphotericin B↗
PubMed1998

Incorporation of the acetylcholine receptor dimer from Torpedo californica in a peptide supported lipid membrane investigated by surface plasmon and fluorescence spectroscopy.

The dimer species (M(r) 580,000) of the nicotinic acetylcholine receptor, isolated from the electric organ of Torpedo californica, was incorporated into a thiopeptide supported lipid bilayer. The incorporation was achieved by fusion of liposomes with reconstituted receptor onto a gold-supported thiopeptide lipid monolayer. Surface plasmon resonance spectroscopy (SPS) was used to monitor in real time the fusion process as well as the specific binding of the antagonist alpha-bungarotoxin. A recently developed extension of SPS offering enhanced sensitivity and specificity, surface plasmon fluorescence spectroscopy (SPFS), was then used to monitor subsequent binding of the monoclonal WF6 and polyclonal antibody, respectively. The latter was fluorescence labeled with Cy5. The different binding assays indicate the successful incorporation of the receptor in the lipid bilayer.

Animals↗
PubMed1998

Abdominal lymphomas, convulsive seizure and coma: a case of successfully treated, advanced Whipple's disease with cerebral involvement.

Whipple's disease is a rare, generalized inflammatory disorder due to the recently described bacterium Tropheryma whippelii. We report an unusual, successfully treated case of a 32-year-old woman, who presented with a 25 month history of large abdominal lymphomas, polyserositis and cachexia. The diagnosis of Whipple's disease was confirmed by duodenoscopy, lymph node and duodenal histology and polymerase chain reaction analysis of biopsy material and cerebrospinal fluid. A prolonged convulsive seizure with a subsequent 5 day period of coma were interpreted as signs of cerebral involvement. Under antibiotic treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) the patient recovered completely, CT scans showed a complete regression of abdominal lymphomas. The therapy was continued over 18 months without the occurrence of a relapse.

Abdominal Neoplasms↗
PubMed1990

Evaluation of the kinetics of the intracellular reduction of 2,6-dichlorophenolindophenol in normal and transformed hepatocytes measured by amperometric methods.

Amperometric methods were used to study the kinetics of intracellular reduction of 2,6-dichlorophenolindophenol (DCIP) in normal and transformed hepatocytes with glucose and succinate as substrates. The curves showing the formation of DCIPred as a function of time were biphasic, the first part obeying the equation of a pseudo-first-order reaction, the final part corresponding to Michaelis-Menten kinetics. A statistical method was used to estimate pseudo-first-order rate constants k as well as Km and Vmax values. At saturating glucose concentrations k, Km and Vmax values were higher in normal compared to transformed cells. Decreasing glucose concentrations revealed lowered saturation concentrations in tumour cells compared to normal cells. With succinate as substrate for hepatocytes, k values were higher than with glucose, while Km and Vmax were about the same. Hepatoma cells did not metabolize succinate. K values could be attributed to intracellular dehydrogenase activities including cytosolic and mitochondrial processes. Differences in pseudo-first-order rate constants between normal and tumour cells may therefore represent characteristic alterations associated with transformation.

2,6-Dichloroindophenol↗
PubMed1990

Investigation by amperometric methods of intracellular reduction of 2,6-dichlorophenolindophenol in normal and transformed hepatocytes in the presence of different inhibitors of cellular metabolism.

The reduction of 2,6-dichlorophenolindophenol (DCIP) was measured by amperometric methods in Morris hepatoma 3924A cells, normal isolated rat hepatocytes and in mitochondria isolated from normal rat liver. The influence of aerobic and anaerobic atmospheres and of various inhibitors of cellular metabolism, especially of the respiratory chain (KCN, NaN3, oligomycin), on DCIP-reduction were studied using glucose, succinate, beta-hydroxybutyrate, alpha-keto-glutarate and oxalacetate as substrates. Under the influence of KCN and oligomycin the velocity of DCIP-reduction was increased in both cell types. Azide showed a similar effect on tumour cells and to a lower extent on hepatocytes. Using isolated mitochondria total DCIPred was increased by KCN and azide using various mitochondrial metabolites as substrates and with ADP/Pi present. The effects of KCN, azide and oligomycin could be explained by taking DCIP as an artificial coupling site in mitochondria which is only used when oxygen is absent or when the respiratory chain is blocked by inhibitors of cytochrome oxidase. Evaluation of the reaction kinetics revealed differences between normal and transformed cells in terms of the pseudo-first-order rate constants and the activity of overall oxidoreductases. The results apparently reflect quantitative differences in enzymatic equipment and the metabolic pathways predominating in normal and neoplastic cells.

2,6-Dichloroindophenol↗
PubMed1990

Glycoconjugate pattern of membranes in the acinar cell of the rat pancreas.

Lectin-binding studies were performed at the ultrastructural level to characterize glycoconjugate patterns on membrane systems in pancreatic acinar cells of the rat. Five lectins reacting with different sugar moieties were applied to ultrathin frozen sections: concanavalin A (ConA): glucose, mannose; wheat-germ agglutinin (WGA): N-acetylglucosamine, sialic acid; Ricinus communis agglutinin I (RCA I): galactose; Ulex europaeus agglutinin I (UEA I): L-fucose; soybean agglutinin (SBA): N-acetylgalactosamine). Binding sites of lectins were visualized either by direct conjugation to colloidal gold or by the use of a three-step procedure involving additional immune reactions. The rough endoplasmic reticulum and the nuclear envelope of acinar cells was selectively labelled for ConA. The membranes of the Golgi apparatus bound all lectins applied with an increasing intensity proceeding from the cis- to the trans-Golgi area for SBA, UEA I and WGA. In contrast RCA I selectively labelled the trans-Golgi cisternae. The membranes of condensing vacuoles and zymogen granules were labelled for all lectins used although the density of the label differed between the lectins. In contrast the content of zymogen granules failed to bind SBA and WGA. Lysosomal bodies (membranes and content) revealed binding sites for all lectins used. The plasma membranes were heavily labelled by all lectins except for SBA which showed only a weak binding to the lateral and the apical plasma membrane. These results are in accordance to current biochemical knowledge of the successive steps in the glycosylation of membrane proteins. It could be demonstrated, that the cryo-section technique is suitable for the fine structural localisation of surface glycoconjugates of plasma membranes and internal membranes in pancreatic acinar cells using plant lectins.

Animals↗
PubMed1988

Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation.

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.

Acute Disease↗
PubMed1987

[Diagnostic procedure in suspected Sjögren syndrome].

Basing on anamnestic and clinical findings in Sjögren's syndrome, methods of examination of the salivary glands are outlined. The flow rate and composition of the saliva, especially sodium and IgM contents, are important points of diagnosis. Serological methods are described, such as examination of antibodies to nuclear antigens and their subunits SS-A and SS-B. Labial salivary gland biopsy rounds off the diagnostic procedure. Patients with Sjögren's syndrome must be controlled regularly because of the above-average risk of developing non-Hodgkin lymphoma.

Adult↗