Search PubMed⌕ Search

Biomedical subjects

D Seidel

Publications and source records attributed to D Seidel.

At least 91 records · Page 5Linked to original sources
PubMed1996

Cross-linked iron dextran is an efficient oral phosphate binder in the rat.

BACKGROUND: There is a need for alternative oral phosphate binders. In-vitro studies showed that iron(III)oxide-hydroxide-modified cross-linked dextran is a promising, insoluble phosphate-binding agent. The present study was designed to assess its in-vivo efficacy and safety in the rat. STUDY, DESIGN AND METHODS: Iron(III)oxide-hydroxide modified dextran beads were mixed with normal rat feed in a proportion of 8% by weight. With this formula rats were fed for 4 weeks. A control group received the same diet without added phosphate binder. Samples of blood, urine, and faeces were taken from each animal before the phosphate binder was administered, 2 weeks later, and at the end of the examination period (day 29). Phosphate, calcium, iron were analysed in the blood samples. Calcium and phosphate concentrations were determined in the urine, phosphate, calcium, and iron concentrations in the excrements. Stability of the material in the duodenum was also simulated. RESULTS AND CONCLUSIONS: The results demonstrate an excellent phosphate-binding capacity of the material and a good tolerance during the intestinal passage. No significant chemical or enzymatic degradation, histological alterations, or other treatment-related macroscopic findings were recorded. The present efficacy and toxicity study has shown effective phosphate binding with no toxicity and no iron release after ingestion of this novel phosphate binding agent. We propose clinical evaluation studies to assess whether similar efficacy and safety can be shown in humans.

Administration, Oral↗
PubMed1996

Early prediction of outcome in score-identified, postcardiac surgical patients at high risk for sepsis, using soluble tumor necrosis factor receptor-p55 concentrations.

OBJECTIVE: To investigate the prognostic value of increased serum concentrations of soluble tumor necrosis factor (TNF) receptors in patients at high risk for sepsis. DESIGN: Prospective study. SETTING: Cardiac surgical intensive care unit in a University Hospital. PATIENTS: Those 27 of 870 consecutive postcardiac surgical patients who met a previously validated high-risk criterion for imminent sepsis (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 24 on the first postoperative day [day 1]). In this population, systemic inflammatory response syndrome was present in 96% of the patients and the in-hospital mortality rate was 30%. In addition, ten postcardiac surgical patients with an uncomplicated course (mortality rate 0%) were studied for comparison. INTERVENTIONS: Blood sampling for measurements of serum concentrations of TNF and soluble TNF receptors 55 kilodalton (TNF receptor-p55) and 75 kilodalton (TNF receptor-p75) on days 1, 2, 3, and 5. MEASUREMENTS AND MAIN RESULTS: Compared with the ten patients with an uncomplicated course (group A), the high-risk patients had significantly higher baseline (day 1) serum concentrations of soluble TNF receptor-p55 (9.2 vs. 4.2 ng/mL) and soluble TNF receptor-p75 (9.2 vs. 5.5 ng/mL). These high-risk patients could be further differentiated into two subgroups: one (B) with a prompt decrease in APACHE II score and a good prognosis (mortality rate 0%) and another (C) with a persisting high risk of sepsis and mortality rate (40%, p < .05). Although baseline APACHE II score was similar in both high-risk subgroups, soluble TNF receptor-p55 concentrations were significantly higher in subgroup C compared with subgroup B already at baseline (10.7 vs. 4.7 ng/mL). The receiver operating characteristic curve for subgroup classification by soluble TNF receptor-p55 was in a discriminating position with an area (0.773 +/- 0.096), confirming soluble TNF receptor-p55 as a predictor of mortality. TNF and soluble TNF receptor-p75 concentrations were less predictive at baseline. CONCLUSIONS: This study suggest that increased soluble TNF receptor-p55 concentrations in the serum of postcardiac surgical patients allow earlier prognostication of subsequent hospital course than APACHE II scores alone. This study further suggests that the combination of physiologic scores and cytokine receptor measurements could improve the predictive power of early postoperative risk stratification.

APACHE↗
PubMed1996

H.E.L.P. apheresis therapy in the treatment of severe hypercholesterolemia: 10 years of clinical experience.

In collaboration with B. Braun Melsungen AG, Germany, we were able to develop the heparin-mediated extracorporeal low-density lipoprotein (LDL) fibrinogen precipitation (H.E.L.P.) system and to introduce it into clinical use. The H.E.L.P. apheresis system is the most potent technique to reduce at the same time LDL, lipoprotein (a) (Lp[a]), and fibrinogen plasma concentrations if the physiological clearing mechanisms are insufficient and if diet and drugs fail to achieve a target concentration of 100 mg/dl LDL-cholesterol or lower, required for secondary prevention of coronary heart disease. The H.E.L.P. LDL apheresis system also improves plasma viscosity and microcirculation efficiently. The clinical experience with the H.E.L.P. system has proved its clinical utility; regression of coronary heart disease occurs, a decrease in events of coronary heart disease takes place, and acute as well as chronic impairment of microcirculation shows a remarkable improvement with H.E.L.P. therapy. For the future, the availability of this safe and efficient apheresis technique may help many patients who previously could not be treated adequately.

Adsorption↗
PubMed1996

Sensitive methods to study human apolipoprotein B metabolism using stable isotope-labeled amino acids.

The objective of the study was to develop a sensitive method using stable isotope-labeled tracers that would permit the determination of apolipoprotein B (apoB) metabolism in very low-density lipoprotein subfractions (VLDL1, Sf 60-400; VLDL2, Sf 20-60), intermediate-density lipoprotein (IDL, Sf 12-20), and low-density lipoprotein (LDL, Sf 0-12). Six normolipidemic subjects were given trideuterated leucine, and its clearance from plasma and appearance in the four apoB-containing lipoprotein fractions were followed by use of a highly sensitive gas chromatography-mass spectrometry technique in which the m + 3-to-m + 2 ion ratio was selectively monitored. This analytic approach permitted the precise measurement of low enrichments in IDL and LDL and extension of the turnover out to 250-300 h. A compartmental model was developed to derive rate constants from the plasma and apoB enrichment curves. The model was uniquely identifiable once parameter dependencies had been introduced to reduce the number of unknowns. Values were obtained for apoB input into all lipoprotein density intervals, together with rates of interconversion and catabolism; these agreed well with results from radioiodinated tracer experiments. An alternative model structure was also explored in which input occurred only into VLDL1. Altering the protocol of tracer administration (bolus vs. primed constant infusion) and dose (over a 10-fold range) had no influence on the results obtained. The analytic and modeling approach described will permit stable isotopes to be used to elucidate key features of apoB metabolism in normal and pathological states.

Adult↗
PubMed1996

Prediction of type 1 diabetes.

Prediction of type 1 diabetes is largely based on islet cell antibodies, but may be improved by combined analysis with other markers. We conducted a screening of first-degree relatives of type 1 diabetic patients in Germany using islet cell antibodies (ICA, indirect immunofluorescence on human pancreas) and insulin autoantibodies (IAA, radioimmunoassay) as screening markers. Of 1460 relatives tested, 2.3% (n = 33) were identified to be ICA+ (> or = 10 JDFu) and 1.9% (n = 27) to be IAA+ (> or = 50 nU/ml) in at least two subsequent serum samples. Of 44 antibody-positive relatives, 17 (39%) progressed to clinical insulin-dependent diabetes mellitus (IDDM) within 5 years. Life-table analysis showed a 58% risk of IDDM for ICA+ and 46% risk for IAA+ individuals. ICA combined with IAA gave a risk of 67% (p < 0.02 compared with ICA-, n.s. compared with IAA-). Of all relatives who progressed to clinical IDDM, only one was negative for ICA, but 6 were negative for IAA, resulting in a sensitivity of 94% for ICA and 65% for IAA. All antibody-positive relatives were characterized for HLA DR and DQ markers by genotyping. Relatives with 2 non DR3/ non-DR4 (DRx/x) alleles had no risk of IDDM, although they were consistently positive for one or more antibody specificities. We conclude that IAA screening is less sensitive than screening with ICA and relatives who lack ICA rarely progress to clinical disease. HLA analysis may be useful among antibody-positive relatives to define subgroups with a low risk of progression to exclude those from future intervention trials.

Autoantibodies↗
PubMed1996

The H.E.L.P. system: an efficient and safe method for plasma therapy in the treatment of severe hypercholesterolemia.

The H.E.L.P. procedure (heparin-induced extracorporeal low density lipoprotein: fibrinogen precipitation) provides an efficient means of lowering high concentrations of low density lipoprotein (LDL) in severe hypercholesterolemia, with the additional effect of lowering lipoprotein(a) and fibrinogen, while high density lipoprotein levels are increased during long-term treatment. The H.E.L.P. treatment also significantly improves plasma viscosity, erythrocyte aggregation and erythrocyte filtration. Overall treatment tolerance is very good, and no major complications have been observed after approximately 70,000 single treatment sessions. Some patients are treated for more than 10 years. In combination with HMG-CoA reductase inhibitors, a mean interval value of -75% to -80% for LDL as compared to the starting concentration may be achieved. The treatment has the advantage that the patient is not exposed to foreign proteins or compounds, with their attendant immunological problems. It displays a high degree of reproducibility and a standardized capacity, guaranteeing a constant therapy independent of the clinic or institution performing the treatment. The clinical experience with the H.E.L.P. system has proved its clinical utility--there is a regression of coronary heart disease, a decrease in coronary heart disease events, and a remarkable improvement in acute as well as chronic impairment of microcirculation. For the future, the availability of this safe and efficient apheresis technique may provide help for many patients who previously could not be treated adequately.

Adult↗
PubMed1995

Evaluation and routine application of the novel restricted-access precolumn packing material Alkyl-Diol Silica: coupled-column high-performance liquid chromatographic analysis of the photoreactive drug 8-methoxypsoralen in plasma.

A fully automated coupled-column HPLC method for on-line sample processing and determination of the photoreactive drug 8-methoxypsoralen (8-MOP) in plasma has been developed. The method is based on the novel internal-surface reversed-phase precolumn packing materials Alkyl-Diol Silica (ADS). This new family of restricted-access materials has a hydrophilic, electroneutral outer particle surface and a hydrophobic internal pore surface. The supports tolerate the direct and repetitive injection of proteinaceous fluids such as plasma and allow a classical C18-, C8- or C4-reversed-phase partitioning at the internal (pore) surface. The total protein load, i.e. the lifetime of the precolumn used in this study (C8-Alkyl-Diol Silica, 25 microns, 25 x 4 mm I.D.), exceeds more than 100 ml of plasma. 8-MOP was detected by its native fluorescence (excitation 312 nm, emission 540 nm). Validation of the method revealed a quantitative and matrix-independent recovery (99.5-101.3% measured at five concentrations between 21.3 and 625.2 ng of 8-MOP per milliliter of plasma), linearity over a wide range of 8-MOP concentrations (1.2-3070 ng of 8-MOP/ml, r = 0.999), low limits of detection (0.39 ng of 8-MOP/ml) and quantitation (0.79 ng of 8-MOP/ml) and a high between-run (C.V. 1.47%, n = 10) and within-run (C.V. 1.33%, n = 10) reproducibility. This paper introduces coupled-column HPLC as a suitable method for on-site analysis of drug plasma profiles (bedside-monitoring).

Calibration↗
PubMed1995

Coupled-column liquid chromatographic analysis of epirubicin and metabolites in biological material and its application to optimization of liver cancer therapy.

A specific, sensitive and fully automated coupled-column LC method for the determination of the anthracycline cytostatic epirubicin and four metabolites in the biological materials human plasma, liver homogenate and liver tumour homogenate has been developed. System-integrated sample processing was achieved using a new restricted access silica precolumn packing. This porous Alkyl-Diol Silica (ADS) was specially designed for the direct and repetitive injection of proteinaceous samples. It consists of a hydrophilic and electroneutral external particle surface (glyceryl-residues) and a hydrophobic reversed-phase internal surface (butyryl-, octanoyl- or octadecyl-residues). These bimodal chromatographic properties allow retention of low molecular analytes by classical RP-chromatography exclusively at the lipophilic pore surface. Macromolecular constituents of the sample matrix (e.g. proteins) are size-excluded by 5 nm pores and quantitatively eliminated in the interstitial void volume. On-line analysis was performed by coupling a C4-Alkyl-Diol precolumn (20 x 4 mm i.d., particle size 25 microns) and LiChrospher RP Select B analytical column (250 x 4 mm i.d., particle size 5 microns) via an electrically driven six-port valve. Separation of the parent compound and its metabolites was achieved with a mobile phase consisting of water (0.1% triethylamine, v/v, pH 2.0 adjusted with trichloroacetic acid)-acetonitrile (70:30, v/v) at a flow rate of 1 ml min-1. The analytes were detected using their natural fluorescence (excitation 445 nm, emission 560 nm). The method described is used for the determination of pharmacokinetics of epirubicin and its metabolites in order to evaluate and optimize treatment regimen of liver cancer chemoembolization therapy.

Chromatography, Liquid↗
PubMed1995

Low atherosclerotic response of a strain of rabbits to diet-induced hypercholesterolemia.

In this report we describe the development of two rabbit strains, HAR (high atherosclerotic response) and LAR (low atherosclerotic response), and their propensities to develop atherosclerosis in the aorta despite similar levels of diet-induced hypercholesterolemia. Sixty-two randomly selected male New Zealand White rabbits were fed a cholesterol-enriched diet (0.5%) for 84 days and developed 57 +/- 25% sudanophilic lesions of the aortic surface; 12 rabbits showed a low atherosclerotic response (0% to 30% surface involvement), and 22 rabbits showed a high atherosclerotic response (70% to 100% surface involvement). The offspring of rabbits with low atherosclerotic response were used for breeding the strain of rabbits resistant to atherosclerosis (LAR strain), while the offspring of rabbits with high atherosclerotic response were used for breeding the HAR strain. Controlled breeding was started after the 4th generation and performed for the subsequent 6 generations. Thus, in the LAR rabbits the lipid-stainable surface area of aorta amounted to only 27 +/- 17% after 112 days of cholesterol feeding. On the other hand, in HAR rabbits, aortic surface involvement reached 85 +/- 25% after 112 days on the cholesterol-enriched diet. The measurements of surface area involvement were corroborated also by a significantly lower, chemically determined cholesterol content of the aorta in LAR rabbits. Plasma lipids and lipoproteins were determined at baseline, after 21 and 42 days of cholesterol feeding, and at the time the animals were killed. The plasma cholesterol concentrations of cholesterol-fed HAR and LAR rabbits showed a 13-fold increase after 21 days and a 21-fold increase after 84 days on the cholesterol diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Simvastatin added to ursodeoxycholic acid does not enhance disappearance of gallstone fragments after shock wave therapy.

Inhibitors of the HMG-CoA reductase have been shown to further reduce the biliary cholesterol saturation in patients treated with oral bile acids for cholesterol gallbladder stones. It was the aim of our study to evaluate the efficacy of simvastatin in addition to ursodeoxycholic acid in the dissolution of gallstone fragments after shock wave lithotripsy and adjuvant bile acid dissolution therapy. Eighteen patients with a single radiolucent gallbladder stone and a serum cholesterol of more than 250 mg/dl were randomly assigned to receive either ursodeoxycholic acid alone (750 mg per day, group A, n = 9) or in combination with simvastatin (20 mg per day, group B, n = 9) for the dissolution of the gallstone fragments generated by extracorporeal shock wave lithotripsy. The two groups were well matched regarding their baseline characteristics. At the primary end point of the study 6 months after lithotripsy, there was no difference between the groups in the rate of gallstone disappearance with 4 of 9 patients being stone free in each group. As evaluated by life table analysis, even further follow-up showed no significant difference between the groups (P = 0.8). In group B, serum cholesterol levels decreased by 22% at 3 months (P = 0.01 vs. baseline) and by 24% at six months (P = 0.02) during treatment while no significant change was observed in group A. With both regiments, no adverse effects were observed. While simvastatin added to ursodeoxycholic acid resulted in a decrease of elevated serum cholesterol levels in gallstone patients, it did not enhance stone disappearance after shock wave lithotripsy and adjuvant bile acid dissolution therapy.

Anticholesteremic Agents↗
PubMed1995

[Therapy of hypercholesterolemia after heart transplantation with the HMG-CoA reductase inhibitor simvastatin in long-term follow-up].

The problem of hypercholesterolemia following heart transplantation (HTx) is often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivates of nicotinic acids and fibrates were not successful due to Cyclosporin A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial, we investigated the effects of monotherapy with the HMG-CoA-reductase inhibitor Simvastatin in heart transplant recipients. The study included 70 patients (Simvastatin n = 37, control group n = 33). Eight patients died within the first 3 month postoperatively following HTx. Purpose of the study was adjustment of LDL-cholesterol-values in the Simvastatin-treated group to < 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol-plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < .001). In the same period the mean HDL-cholesterol values increased by approximately 15% in both groups. The ratio of LDL-/HDL-cholesterol was significantly lower in the Simvastatin treated group (2.28) than in the control group (2.94) (p < .01). There was no significant difference in Lp(a)-values. No adverse effects were observed within the following period of 24 months, particularly no increase in the frequency of rejection episodes. The drug induced hypercholesterolemia following HTx could be treated safely and effectively by low-dose Simvastatin.

Adult↗
PubMed1995

Efficacy of lipid apheresis: definitions and influencing factors.

The comparison of efficiency of currently available lipid apheresis systems has been hampered by different definitions of efficacy and poorly controlled apheresis conditions. This paper suggests definitions of efficacy and standardization of its determinants. The acute efficacy of risk factor reduction reflects the relative decrease of pathogen by a single treatment session compared to preapheresis levels. Standardization of treated plasma volume in relation to the patients plasma volume and correction of changes in plasma volume during the procedure are mandatory. Its determination is most useful in the technical evaluation of new systems. The long-term efficacy of risk factor reduction as compared to baseline is determined by mean interapheresis levels of e.g. LDL-C in the pseudo-steady-state after about 3 months of regular treatment. It is the major criterion for potential regression of coronary artery disease and absolute average plasma levels of 120 < or = mg/dl LDL-C should be attained. It is influenced by the acute efficacy of the system, apheresis frequency and rebound kinetics. The clinical efficacy is defined by apheresis induced reduction of coronary morbidity and mortality. It is influenced by long-term risk factor reduction, the selectivity of the system as well as the control of non-lipid risk factors. Apheresis related effects on coronary artery disease comprise functional improvements of hemorheology and vasomotion as well as morphological benefits like regression of luminal narrowing and plaque stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗