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Biomedical subjects

Dietrich Seidel

Publications and source records attributed to Dietrich Seidel.

23 records · Page 2Linked to original sources

Simvastatin initiated early after heart transplantation: 8-year prospective experience.

BACKGROUND: Randomized clinical trials have demonstrated that the use of statins in heart transplant patients lowers cholesterol levels and significantly reduces mortality and the development of transplant vasculopathy. The aim of the present study was to test these effects and the safety of statin therapy over an 8-year period. METHODS AND RESULTS: In 1991, a prospective, randomized, unmasked study was initiated to compare the efficacy of simvastatin, started on the fourth postoperative day (n=35), with that of dietary therapy alone (n=37). Because of significantly improved survival and a lower incidence of transplant vasculopathy, most patients in both groups received statins as open-label prescriptions after 4 years. After 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin group versus 59.5% in the control group (P<0.006 by log rank; hazard ratio, 0.24; 95% CI, 0.08 to 0.71). Deaths in the simvastatin and control groups were due to transplant vasculopathy (1 versus 4; P<0.2), severe transplant rejection (1 versus 5; P<0.1), malignancies (0 versus 3; P<0.1), and other causes (2 versus 3; P<0.7). The incidence of transplant vasculopathy confirmed by angiography was 24.4% in the simvastatin group versus 54.7% in the control group (P<0.02 by log rank). There was no difference in organ function between the 2 groups. No severe adverse effects of the therapy were observed up to the end of the 8-year observation period. CONCLUSIONS: Simvastatin therapy initiated early after heart transplantation leads to significantly better 8-year survival rates and a significantly lower incidence of transplant vasculopathy without impairment of organ function or severe adverse effects.

Adult↗

Case reports on emergency treatment of cardiovascular syndromes through heparin-mediated low-density lipoprotein/fibrinogen precipitation: a new approach to augment cerebral and myocardial salvage.

We report the first experiences with HELP apheresis as an emergency treatment for acute cardiovascular syndromes; two patients who were not eligible for lysis therapy and catheter intervention were treated with HELP apheresis instead. Both patients had a most severe, generalized atherosclerosis and reached the hospital too late for conventional measures. In both cases, the use of the apheresis dramatically improved the clinical situation to such an extent that the possibilities of this apheresis system urge further investigation.

Blood Component Removal↗

Long-term prevention of premature coronary atherosclerosis in homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (FHH) leads to severe premature atherosclerosis. A 22-year-old woman with FHH has been treated with a combination of H.E.L.P. apheresis (heparin-mediated extracorporeal LDL precipitation) and statins for 15 years. The combined treatment maintained a plasma LDL-cholesterol reduction from baseline of 840 to 122 mg/dL (85% reduction). In addition, H.E.L.P. apheresis reduced the elevated lipoprotein(a) and fibrinogen levels by 60% to 70%. All xanthomata disappeared. There is no evidence of premature atherosclerosis studied by means of electron beam computed tomography and (13)N-ammonia positron emission tomography: The entire coronary vasculature is free of calcifications. Her myocardial blood flow at rest (87 mL/100 g/min) and during stress (308 mL/100 g/min) and the coronary flow reserve (3.5) are normal after H.E.L.P. treatment. This case demonstrates the efficacy and safety of the combined treatment of H.E.L.P. apheresis and statins even in serious cases of FHH.

Adult↗

Quantification of sirolimus by liquid chromatography-tandem mass spectrometry using on-line solid-phase extraction.

Quantification of the new immunosuppressant sirolimus (syn. rapamycin; Rapamune) in whole blood by chromatography is essential for its clinical use since no immunoassay is available although monitoring is mandatory. Here we report on a rapid and convenient liquid chromatography (LC-tandem mass spectrometry method and describe our practical experience with its routine use. Whole blood samples were hemolyzed and deproteinized using an equal volume (150 microl) of a mixture of methanol/zinc sulfate solution containing the internal standard desmethoxy-rapamycin. After centrifugation, the clear supernatants were submitted to an on-line solid-phase extraction procedure using the polymeric Waters Oasis HLB material, with elution of the extracts onto the analytical column in the back-flush mode by column switching. For analytical chromatography a RP-C18 column was used with 90/10 methanol/2 mM ammonium acetate as the mobile phase. A 1:10 split was used for the transfer to the mass spectrometer, a Micromass Quattro LC-tandem mass spectrometry system equipped with a Z-spray source and used in the positive electrospray ionization mode. The following transitions were recorded: sirolimus, 931>864 m/z, and desmethoxy-rapamycin (I.S.), 901>834 m/z. The analytical running time was 5 min, including on-line extraction. The method has a linear calibration curve (r>0.99; range 1.6-50 microg/l) and is rugged and precise with monthly CVs <7% at a sirolimus concentration of 13.1 microg/l in routine use; the instrumentation proved to be reliable and required minimal maintenance. Clin Chem

Chromatography, Liquid↗

Serum cholesterol levels in neutropenic patients with fever.

Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapy-induced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapy-induced neutropenia and correlated it with clinical outcome. Patients with fever (>38.5 degrees C) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever non-survivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.49-2.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.68-4.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and non-survivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients.

Antigens, CD↗