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Biomedical subjects

E Wieland

Publications and source records attributed to E Wieland.

At least 55 records · Page 3Linked to original sources
PubMed1998

Experimental studies on the role of antibody fragments in cancer radio-immunotherapy: Influence of radiation dose and dose rate on toxicity and anti-tumor efficacy.

Whereas bivalent fragments have been widely used for radio-immunotherapy, no systematic study has been published on the therapeutic performance of monovalent conjugates in vivo. The aim of our study was, therefore, to determine the therapeutic performance of (131)I-labeled Fab as compared to bivalent conjugates and to analyze factors that influence dose-limiting organ toxicity and anti-tumor efficacy. The maximum tolerated doses (MTDs) and dose-limiting organ toxicities of the (131)I-labeled anti-CEA antibody MN-14 [IgG, F(ab')2 and Fab] were determined in nude mice bearing s.c. human colon cancer xenografts. Mice were treated with or without bone marrow transplantation (BMT) or inhibition of the renal accretion of antibody fragments by D-lysine or combinations thereof. Toxicity and tumor growth were monitored. Radiation dosimetry was calculated from biodistribution data. With all 3 (131)I-labeled immunoconjugates [IgG, F(ab')2 and Fab], the red marrow was the only dose-limiting organ; MTDs were 260 microCi for IgG, 1,200 microCi for F(ab')2 and 3 mCi for Fab, corresponding to blood doses of 17 Gy, 9 Gy and 4 Gy, respectively. However, initial dose rates were 10 times higher with Fab as compared to IgG and 3 times higher as compared to F(ab')2. The MTD of all 3 immunoconjugates was increased by BMT by approximately 30%. In accordance with renal doses below 10 Gy, no signs of nephrotoxicity were observed. Despite lower absorbed tumor doses, at equitoxic dosing, Fab fragments were more effective at controlling tumor growth than the respective bivalent fragment or IgG, probably due to higher intratumoral dose rates. Our data indicate that the improved anti-tumor effectiveness of antibody fragments as compared to IgG and the higher myelotoxicity at comparably lower red marrow doses are most likely due to the higher initial dose rates observed with antibody fragments.

Animals↗
PubMed1998

[Morphometric analysis of roentgen images of the spine for diagnosis of osteoporosis-induced fracture].

The European Vertebral Osteoporosis Study (EVOS) is one of the largest studies to investigate the prevalence of osteoporosis related vertebral fractures in a population based cross-sectional study. One of the main tasks was to create standards and logistics to obtain uniform and comparable radiographs in all 36 European centers. Furthermore the central reading of the X-rays and the morphometry of the vertebral bodies were 2 important challenges. This paper describes the standardized patient positioning and making of the radiographs as well as their morphometry, reading, and evaluation.

Aged↗
PubMed1998

[Prevalence of vertebral spinal deformities in women and men in Germany. EVOS group in Germany].

BACKGROUND: The prevalence of radiographically defined vertebral deformities, as a marker of vertebral osteoporosis, was calculated in a population based cross-sectional survey in Germany. METHOD: Lateral spine X-rays were taken according to a standardized protocol and evaluated centrally. Three thousand nine hundred and eighty subjects (2064 male and 1916 female) aged 50 to 79 years, have been examined in 8 German centers. RESULTS: Based on McCloskey's method of deformity definition the age-standardized mean prevalence of vertebral deformities in Germany was 10.2% for males and 10.5% for females. Based on the definition by Melton/Eastell a significant higher prevalence was calculated (males 17.8%, females 18.7%). The prevalence increased with age in both sexes with a steeper increase in females. There was no difference in East and West German populations. There were substantial variations between the centers regarding the prevalence of deformities in females and males.

Aged↗
PubMed1998

Activity of free radical scavenging enzymes in red cells and plasma of patients undergoing extracorporeal low-density lipoprotein apheresis.

There is evidence that reactive oxygen species (ROSs) are generated in extracorporeal circuits. Free radical scavenging enzymes (FRSEs) such as glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) protect against the damaging effect of ROSs. The influence of extracorporeal treatment on FRSE activity was investigated in the plasma and red blood cells (RBCs) of 21 patients undergoing regular low-density lipoprotein (LDL) apheresis. The FRSEs GSSG-R, GSH-Px, and SOD were measured. Determinations were made before and after a single treatment. Because all apheresis patients suffered from coronary heart disease (CHD), 201 CHD patients and 90 individuals without CHD, neither group undergoing apheresis, served as controls. In apheresis patients, GSH-Px (33.9+/-8.2 U/g Hb) and GSSG-R (7.6+/-0.9 U/g Hb) activities were increased whereas SOD activity (5.4+/-1.5 U/g Hb) was decreased in RBCs before a single treatment compared to controls. Plasma FRSEs of apheresis patients were not different from those of controls. There was no effect of a single treatment on FRSEs in RBCs. However, a significant decrease in plasma GSH-Px activity (209.9+/-24.9 U/ml) due to the extracorporeal treatment was observed. These data show that long-term extracorporeal therapy with LDL apheresis modulates the activity of antioxidant enzymes in RBCs whereas a single treatment was without major effect on FRSE activity in RBCs and plasma, except for plasma GSH-Px.

Adult↗
PubMed1998

Oxidative stress during dialysis: effect on free radical scavenging enzyme (FRSE) activities and glutathione (GSH) concentration in granulocytes.

BACKGROUND: Living cells are protected by free radical scavenging enzymes against oxygen radical-mediated damage. It has been suggested that granulocytes are activated on the surface of dialyser membranes, resulting in the generation of free radicals. We have recently reported a lack of plasma lipid peroxidation and unchanged glutathione peroxidase (GSH-Px) as well as glutathione reductase (GSSG-R) activities in red blood cells of haemodialysis patients. However, because mature red cells are free of DNA and RNA, free radical scavenging enzymes (FRSE) cannot be regulated on the gene level in response to an acute oxidative stress. In contrast to erythrocytes, granulocytes are nucleated cells and FRSE protein concentrations can therefore be modulated. METHODS: GSH-Px, GSSG-R, superoxide dismutase (SOD) activities and total glutathione (GSH) were determined spectrophotometrically using a Cobas Fara semi-automatic analyser in granulocytes of 31 healthy blood donors and in 28 patients with chronic renal failure (CRF) for more than 6 months before as well as immediately after a single dialysis treatment. Patients were treated either by haemodialysis (n = 17) using low-flux polysulphone membranes or by haemofiltration (n= 1l) usings high-flux polysulphone membranes. RESULTS: Compared to healthy controls, SOD and GSSG-R activities were increased in granulocytes of HD and HF patients, GSH and GSH-Px were decreased before a single treatment. After dialysis SOD and GSH-PX activities were significantly induced by both HD and HF whereas GSSG-R activities and GSH were decreased. CONCLUSIONS: These results show that the enzymatic defence against oxygen radicals can be induced in granulocytes of patients undergoing regular dialysis treatment, whereas the non-enzymatic defence is compromised as shown by decreased GSH concentrations, both suggesting increased oxidative stress.

Adult↗
PubMed1998

Determination of monoethylglycinexylidide by fluorescence polarization immunoassay in highly icteric serum samples: modified precipitation procedure and HPLC compared.

Hyperbilirubinemia, which frequently occurs in severe liver disease, interferes with the fluorescence polarization immunoassay (FPIA) monoethylglycinexylidide (MEGX) assay manufactured by Abbott Diagnostics. Because the MEGX test is particularly helpful in this clinical situation, strategies have been developed to overcome this problem. Precipitation of serum with the Abbott Digoxin II precipitation reagent eliminates bilirubin. Therefore, we compared FPIA results after precipitation of 81 icteric samples from 27 MEGX tests to results obtained using a validated HPLC method. The precipitation did not substantially alter the performance characteristics of FPIA: detection limit, 8 microg/L; between-days imprecision, 5.3-6.2%; recovery, 102-104% (50-200 microg/L). This pretreatment of serum did not eliminate all interference, and only a poor correlation was observed between serum MEGX concentrations measured with HPLC or modified FPIA (r2 = 0.46; S(y/x) = 20.0 microg/L). In contrast, MEGX formation values calculated by subtraction of the prelidocaine MEGX concentration were in close agreement (r2 = 0.98; S(y/x) = 2.3 microg/L). Because only MEGX formation is clinically relevant, this modified FPIA procedure offers a simple and rapid alternative to HPLC.

Chemical Precipitation↗
PubMed1998

Simultaneous determination of mycophenolic acid and its glucuronide in human plasma using a simple high-performance liquid chromatography procedure.

We describe a reversed-phase HPLC method for determination of total mycophenolic acid (MPA), its free concentration (MPAf), and the glucuronide metabolite (MPAG), based on simple sample preparation and gradient elution chromatography. The compounds were quantified in parallel by absorbance at 254 nm and 215 nm in the internal standard mode. Linearity was verified up to 50 mg/L for MPA and up to 500 mg/L for MPAG (r >0.999). Detection limits at 215 and 254 nm were, respectively, 0.01 and 0.03 mg/L for MPA, and 0.03 and 0.1 mg/L for MPAG. The recovery of MPA was 95-106%; recovery of MPAG was 96-106%. The imprecision (CV) for MPA (0.2-25 mg/L) was <8.4% (254 nm) and <4.4% (215 nm) within day (n = 12) and <9.2% (254 nm) and <6.2% (215 nm) between days (n = 12). The imprecision for MPAG (10-250 mg/L) was <4.9% (254 nm) and <3.4% (215 nm) within day, and <6.1% (254 nm) and <5.9% (215 nm) between days. For quantification of MPAf, 100 microL of ultrafiltrate was applied directly to the column. The detection limit was 0.005 mg/L at 215 nm and 0.015 mg/L at 254 nm. In the range between 18-210 microg/L, the within-day CVs were <11.8% (n = 12) and the between-day CVs were <15.8% (n = 12).

Blood Proteins↗
PubMed1998

Cyclosporin whole blood immunoassays (AxSYM, CEDIA, and Emit): a critical overview of performance characteristics and comparison with HPLC.

Assays with different specificity are used for cyclosporin monitoring in clinical transplantation. A recent survey of 35 centers showed that 86% used immunoassays for cyclosporin A (CsA). In consensus documents the following performance criteria were recommended: (a) imprecision < or = 10% at 50 microg/L and < or = 5% at 300 microg/L; and (b) comparison with the reference method (HPLC) should yield a slope of 0.9-1.1, an intercept of -15 to 15 microg/L, and S(y/x) < or = 15 microg/L. The newly developed CsA assays for the AxSYM (Abbott) and the CEDIA (Boehringer Mannheim) as well as the Emit assay (Behring Diagnostica) were evaluated. Results from samples of heart, kidney, and liver recipients (100 specimens each) were compared with a validated HPLC-ultraviolet detection method. Between-series imprecision (CV) with commercial controls was 5.8% and 1.7% for AxSYM (70 and 300 microg/L), 11% and 5.5% for CEDIA (90 and 200 microg/L), and 8.1% and 4.5% for Emit (63 and 172 microg/L). In the presence of 300 microg/L parent CsA, cross-reactivities were (for AxSYM, CEDIA, and Emit, respectively) 7%, 4%, and none for AM1 (1 mg/L) and 12.6%, 25%, and 6% for AM9 (0.5 mg/L). Comparison with HPLC showed in heart and kidney recipients an average overestimation with the Emit and the CEDIA of approximately 22%, with overestimation in the AxSYM of 32%. In liver recipients, the most challenging patient group, the CEDIA and the AxSYM showed a mean overestimation of 43% and 47%, respectively, and the Emit differed by 31% compared with HPLC. None of the immunoassays fully satisfied the performance criteria recommended in the consensus documents. In terms of specificity, Emit ranks before CEDIA, which ranks before AxSYM. Regarding imprecision, the ranking is AxSYM < Emit < CEDIA. These limitations must be considered when using these assays for therapeutic drug monitoring of CsA in clinical transplantation.

Chromatography, High Pressure Liquid↗
PubMed1997

Acceleration of hepatocellular energy by idebenone during early reperfusion after cold preservation ameliorates heat shock protein 70 gene expression in a pig liver model.

BACKGROUND: Heat shock proteins (HSPs) are induced in the liver after warm ischemia/reperfusion and are thought to be markers of hepatocellular injury and oxidative stress. METHODS: The influence of variable periods of cold storage followed by reperfusion on the expression of HSP70 was studied in the isolated perfused pig liver. Organs were harvested and stored in histidine-tryptophan-ketoglutarate solution at 4 degrees C and then perfused (210 min) in a closed water bath (38 degrees C), which subjects the liver to fluctuating outer pressure. The role of energy depletion, reactive oxygen intermediates, Kupffer cells, and circulating leukocytes in HSP70 expression was determined. RESULTS: HSP70 expression was not detectable in liver tissue before explantation or before reperfusion by Northern blot analysis using a pig HSP70 gene probe. HSP70 expression was observed after reperfusion depending on cold storage time. Kinetics of HSP70 expression monitored by reverse transcriptase polymerase chain reaction showed a rapid increase of mRNA within 1 hr, which was closely associated with delayed recovery of hepatocellular energy charge, as assessed by the ketone body ratio. The inactivation of Kupffer cells, the presence or absence of leukocytes, and the suppression of oxidative stress with the antioxidant idebenone, given during reperfusion, had no influence. However, feeding the animals with idebenone over 7 days before explantation led to a faster recovery of ketone body ratio, paralleled by a substantial suppression of HSP70 expression. CONCLUSIONS: Our data show that HSP70 expression during reperfusion is mainly dependent on the preceding cold storage time and the consecutive delayed recovery of the hepatocellular energy charge.

Animals↗
PubMed1997

Suppression of leukocyte-enhanced cold ischemia/reperfusion injury of liver endothelium with the benzoquinone antioxidant idebenone.

OBJECTIVE: Despite the large body of evidence for a major role of neutrophils and oxidant stress, the exact pathogenesis of the early ischemia/reperfusion injury after cold preservation of the liver is not well understood. The potential benefit of an antioxidant on metabolic liver function during reperfusion has been demonstrated in several studies. MATERIALS AND METHODS: We describe a cold storage/reperfusion damage model with isolated perfused pig livers, where the effects of neutrophils and idebenone, a recently developed benzoquinone antioxidant were studied. The integrity of sinusoidal endothelial cells (SEC) was estimated by hyaluronic acid concentration in perfusate and the expression of endothelial constitutive nitric oxide synthase (ecNOS) after reperfusion and compared to lipid peroxidation and antioxidant content. RESULTS: Hyaluronic acid displayed the highest levels and ecNOS mRNA was most depressed in livers reperfused with neutrophils after 20 h cold storage; this was accompanied by an increase in lipid peroxidation (TBARS) and a breakdown of endogenous lipophilic antioxidants (alpha-tocopherol and coenzyme Q-10). These effects were attenuated, when neutrophils were excluded from reperfusion and almost completely abolished by the addition of 200 mumol/L idebenone. CONCLUSIONS: These data suggest that a leukocyte-mediated damage based on reactive oxygen species markedly contributes to the reperfusion injury of SEC after cold preservation of the liver. Therefore, the presence of effective antioxidants in the early reperfusion phase may be beneficial for liver graft integrity.

Animals↗
PubMed1996

A thermodynamic surface model for caesium sorption on bentonite.

Caesium sorption on Wyoming bentonite MX-80 has been studied in solutions of NaCl, KCl, MgCl(2), CaCl(2), NaNO(3) and Ca (NO(3))(2) of concentrations varying between 0.025 and 1 mol/L, as well as in a weakly saline (I=0.004 ml/L) and a strongly saline (I=0.46 mol/L) natural groundwater. These experiments have been used to derive a thermodynamic model for the interaction of caesium with the bentonite surface in accordance with a surface chemical model, including acid/base reactions developed recently for montmorillonite. The sorption behaviour of caesium on bentonite can be described, within the experimental and model uncertainties, in terms of a one-site ion exchange model. The ion exchange constant obtained for the reaction NaX+Cs(+) left arrow over right arrow CsX+Na(+) (where X represents the ion exchange sites on montmorillonite) is log(10) K(0)(ex)=1.6. Impurities in the bentonite, influencing the concentrations of competing cations, such as Na(+), K(+), Mg(2+) and Ca(2+), have a crucial impact on the sorption of caesium. This impact can be adequately quantified with the present model. The model predictions compare well with sorption data published in the open literature on both Wyoming bentonite MX-80 and other types of bentonite. Distribution coefficients from the literature obtained from both batch and diffusion experiments and varying over four orders of magnitude are reproduced and explained successfully by the model.

Journal Article↗