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Biomedical subjects

U Reinhardt

Publications and source records attributed to U Reinhardt.

At least 19 recordsLinked to original sources
PubMed1999

Fludarabine and epirubicin in the treatment of chronic lymphocytic leukaemia: a German multicenter phase II study.

PURPOSE: Fludarabine has been reported to be the most effective single-agent in previously treated chronic lymphocytic leukaemia (CLL). Based on the in vitro synergism of fludarabine with anthracyclines and on results showing a higher efficacy of CHOP against COP we attempted to improve treatment results with a combination of fludarabine and an anthracycline. PATIENTS AND METHODS: The aim of the multicenter study was to evaluate the rate and duration of remissions and investigate the toxic and immunosuppressive effects of fludarabine and epirubicin in the treatment of CLL in Binet stages B and C as first-line therapy or in first relapse. Thirty-eight patients were treated with fludarabine 25 mg/m2 on days 1-5 and epirubicin 25 mg/m2 on days 4 and 5. RESULTS: The overall response rate (OR) was 82% (95% confidence interval (95% CI): 66%-92%) with a CR rate of 32% (95% CI: 18%-49%). For the 25 previously untreated patients the OR was 92% (95% CI: 74%-99%) including 40% CRs (95% CI: 21%-61%). Granulocytopenia grade 3 occurred in 23% of all evaluable cycles, and grade 4 in 17%. The median remission duration was 19 months (range 6-37 months). CONCLUSION: The results show that the combination of fludarabine and epirubicin is tolerable and highly effective in the treatment of CLL. With the addition of epirubicin to fludarabine, it appears possible to achieve a higher response rate and a more rapid response, especially of nodal manifestations. This regimen can be administered in an outpatient facility except for the first cycle because of the risk of a tumour lysis. The possible benefit of the combination presented here in the treatment of CLL in comparison to single-agent fludarabine treatment is presently under study in a prospective randomized multicenter study.

Adult↗
PubMed1999

[Investigations into synchronisation of heart rate and musical rhythm in a relaxation therapy in patients with cancer pain].

OBJECTIVE: Registration of the influence of musical rhythm on synchronisation and coordination of heart rate. DESIGN: Randomized pilot study. PROBANDS: 28 patients with chronic cancer pain in a stable phase of the disease. INTERVENTION: 14-day training of a relaxation therapy designed for improving the falling asleep, including a 30-minute lullaby-like, rhythmically dominated music with gradually decreasing tempi. No training in the control group. OUTCOME MEASURES: Continuous registration of heart rate and comparison with musical beat on day 1 and 15. Analysis of the degree of synchronisation, i.e. the coordination of systole and musical central time point (1st beat of the 6/8 time alla breve). Recording of the time of falling asleep and registration of the patient's subjective evaluation of the relaxation therapy and the pain intensity using verbal rating scales. Documentation of the use of analgetics. RESULTS: Under the relaxation therapy trained patients showed an increasing synchronisation and coordination of heart rate and musical beat. At a musical tempo between 48 and 42 beats per min a very stable 2 : 3 synchronisation occurred. Trained patients who reported the best relaxing and analgetic effects showed the highest degree of synchronisation. Relaxation therapy led to an improvement of falling asleep and to a decrease in consumption of analgetics. CONCLUSIONS: Lullaby-like music within a special range of tempi can induce a trainable synchronisation of heart rate, functionally associated with the formation and intensity of a relaxation reaction. Further investigations are promising, however, substantial improvements in the measurement and documentation methods are needed.

Adult↗
PubMed1998

Phospholipid source and molecular species composition of 1,2-diacylglycerol in agonist-stimulated rat cardiomyocytes.

OBJECTIVE: The aim was to investigate the consequences of simultaneous stimulation of phospholipase C and D by agonists for the molecular species composition of 1,2-diacylglycerol and phospholipids in cardiomyocytes. METHODS: Serum-free cultured neonatal rat cardiomyocytes were stimulated by endothelin-1, phenylephrine or phorbolester. The molecular species of 1,2-diacylglycerol (in mol%) and those derived from phosphatidylcholine and phosphatidylinositol were analyzed by high-performance liquid chromatography and their absolute total concentration (nmol per dish) by gas-liquid chromatography. Phospholipids were labelled with [14C]glycerol or double-labelled with [14C]16:0 and [3H]20:4n6 for measurements of respectively, the amount of or relative rate of label incorporation into 1,2-diacylglycerol. RESULTS: The major molecular species of 1,2-diacylglycerol in unstimulated cells was found to be 18:0/20:4 (57 mol%). The same species was observed predominantly in phosphatidylinositol (73 mol% compared to 11 mol% in phosphatidylcholine). A significant decrease (about 10 mol%) was found for the 18:0/20:4 species of 1,2-diacylglycerol during stimulation (10-40 min) with endothelin-1 or phorbolester, but not phenylephrine. The results of the double-labelling experiments were consistent with the latter finding: the ratio [3H]20:4 over [14C]16:0 in 1,2-diacylglycerol decreased from 1.70 in the control to 1.40 during 10-min endothelin-1 or phorbolester stimulation, but not during phenylephrine stimulation. The [14C]glycerol incorporation into 1,2-diacylglycerol remained relatively constant under agonist-stimulated conditions as did the total concentration of 1,2-diacylglycerol. CONCLUSIONS: 1,2-Diacylglycerol present in unstimulated cardiomyocytes is likely derived from phosphatidylinositol. During stimulation with endothelin-1 and phorbolester, but not phenylephrine, phosphatidylcholine becomes an increasingly important source for 1,2-diacylglycerol due to sustained activation of phospholipase D. The 1,2-diacylglycerol level remains relatively constant during agonist stimulation which strongly indicates that particular molecular species of 1,2-diacylglycerol more than its total concentration determine the activation of protein kinase C isoenzymes.

Adrenergic alpha-Agonists↗
PubMed1996

Diradylglycerol formation in cholecystokinin-stimulated rabbit pancreatic acini. Assessment of precursor phospholipids by means of molecular species analysis.

The aim of the present study was to assess the origin of the 1,2-diradylglycerols produced during prolonged hormonal stimulation of rabbit pancreatic acini by comparison of their relative molecular species composition with that of the major acinar phospholipids. Both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) consisted of 1,2-diacyl as well as 1-alk-1-2-acyl species. In contrast, phosphatidylinositol (PtdIns), phosphatidylserine and phosphatidic acid existed only in the 1,2-diacyl form. Acinar cells did not contain detectable amounts of 1-alkyl-2-acyl phospholipids. Similarly, the acinar 1,2-diradylglycerol fraction consisted of 1,2-diacylglycerols and 1-alk-1-enyl-2-acylglycerols. Mass 1,2-diradylglycerol measurements revealed that prolonged stimulation with cholecystokinin resulted in a marked and sustained increase in acinar 1,2-diradylglycerol content. Based on the relative amounts of the 1,2-diacyl species present in both the 1,2-diradylglycerol fraction and the individual phospholipids, it is calculated that under control conditions 60% of the 1,2-diacylglycerols originate from PtdCho and 40% from PtdIns, whereas under stimulatory conditions 53% is calculated to be derived from PtdCho, 46% from PtdIns and 1% from PtdEtn. Likewise, it is calculated that in control as well as stimulated acini 100% of the 1-alk-l-enyl-2-acylglycerols originate from plasmenylcholine. Further evidence in favour of the idea that at least a considerable part of the 1,2-diacylglycerols produced during prolonged hormonal stimulation originate from inositolphospholipids is provided by the observation that labeling of phosphatidylinositol 4,5-bisphosphate with inorganic phosphate reached isotopic equilibrium markedly faster under stimulatory conditions as compared to the control situation, which is in agreement with an elevated turnover rate. The data presented support the idea that PtdCho and inositolphospholipids are the major precursors in basal and stimulated 1,2-diradylglycerol production in rabbit pancreatic acini.

Animals↗
PubMed1996

Plasmalogen phospholipids in plasma lipoproteins of normolipidemic donors and patients with hypercholesterolemia treated by LDL apheresis.

Recent evidence indicates that plasmalogen phospholipids are particularly sensitive to oxidation and may possess antioxidative properties. Approximately 4.4%-5.5% of phosphatidylcholine (PC), and 53%-60% of phosphatidylethanolamine (PE) consisted of the plasmalogen phospholipids, plasmenylcholine and plasmenylethanolamine, respectively, in whole plasma, low density lipoprotein (LDL) and high density lipoprotein (HDL) of 11 normolipidemic donors. Of total plasmalogen phospholipids in plasma, slightly more was associated with LDL particles (about 42%) than with HDL (36%). Plasmalogen phospholipid levels were analyzed in 12 patients with familial hypercholesterolemia (FH) regularly treated by LDL apheresis, of whom 6 were supplemented with vitamin E (alpha tocopherol, 400 IU/day), the remaining 6 not receiving the antioxidant. Before apheresis (pre), total plasmalogen phospholipid levels in plasma and LDL (expressed as mumol/mmol cholesterol of compartment) decreased as follows: patients receiving vitamin E > normolipidemia > patients not receiving vitamin E. In both hypercholesterolemic groups, the contents of plasmalogen phospholipids in whole plasma and LDL were 3-5-fold higher than those of vitamin E. Directly after apheresis (post), plasmalogen phospholipid levels in plasma were raised by about 50% in the two hypercholesterolemic groups, mostly due to increases in plasmenylethanolamine levels. Two days after apheresis (48 h post), plasmalogen contents were still elevated in plasma and red blood cell membranes of patients receiving vitamin E, while they had already reached pre-apheresis values in those not supplemented with alpha tocopherol. Molecular species of plasma diacyl phospholipids containing polyunsaturated fatty acids were elevated at pre in patients receiving vitamin E as compared to patients without supplementation. At 48 h post, LDL apheresis induced an increase in these molecular species only in patients receiving vitamin E. In conclusion, the contents of plasmalogen phospholipids in plasma lipoproteins are at least three times higher than those of vitamin E. LDL apheresis raises the level of plasmalogen phospholipids in plasma, the increase persisting longer in patients supplemented with vitamin E. Supplementation with vitamin E appears to protect plasmalogen phospholipids in plasma lipoproteins against oxidative degradation.

Adult↗