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Biomedical subjects

G Klose

Publications and source records attributed to G Klose.

At least 19 recordsLinked to original sources

Thermotropic phase behaviour of the pseudobinary mixtures of DPPC/C12E5 and DMPC/C12E5 determined by differential scanning calorimetry and ultrasonic velocimetry.

The present paper reports on the phase behaviour of the pseudobinary aqueous mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/pentaethylene glycol monododecyl ether (C12E5) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine monohydrate (DMPC)/C12E5. Both systems exhibit a variety of mesophases, such as lamellar gel, liquid crystalline and micellar phases. The phase diagrams show peritectic and eutectic behaviours. The existence of a compound complex is established. From the phase diagrams, the temperature dependence of the solubilisation parameters is obtained. The phase diagrams, especially with respect to the solubilisation process were qualitatively explained assuming that the packing of the constituents plays a dominating role. Finally, differential scanning calorimetry and ultrasonic velocimetry are compared concerning their potentials to determine characteristics of phase transitions in pseudobinary phospholipid/surfactant mixtures.

1,2-Dipalmitoylphosphatidylcholine↗

[Cost-effectiveness of atorvastatin for the prevention of coronary disease. An analysis of the ASCOT study].

BACKGROUND: Increasing health service expenditure, on the one hand, and the politically declared objective of stability of statutory contributions and restriction of public funds, on the other hand, have been central points in the political and social discussion for several years. PATIENTS AND METHODS: Cost-effectiveness of Atorvastatin in primary prevention was analysed by applying the results of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT study) to the German health system. Costs and effectiveness were subject to an extensive sensitivity analysis. RESULTS: The cost-effectiveness of Atorvastatin treatment in Germany is approximately 10,102 Euro (95% CI: 9109; 12,881) per life-year gained. Taking 2004 price reductions into consideration, these values are reduced to 7311 Euro [95% CI: 5197; 10,091) per life-year gained. The robustness of this result was substantiated through extensive sensitivity analyses. CONCLUSION: The administration of the lipid lowering compound Atorvastatin in hypertensive patients with additional coronary heart disease risk factors in Germany is cost-effective.

Adult↗

Cholesterol lowering effect of dietary weight loss and orlistat treatment--efficacy and limitations.

BACKGROUND: Orlistat reduces energy uptake by the impairment of fat digestion and some evidence indicates it also lowers plasma cholesterol. AIM: To examine total, low-density lipoprotein- and high-density lipoprotein cholesterol during a weight reducing regimen, and assess the effect of orlistat in lowering cholesterol levels independent of its weight reducing efficacy. METHODS: A total of 448 patients with elevated cholesterol according to cardiovascular risk factors entered a 2 week single-blind run-in period on a hypocaloric diet. Of 384 patients were subsequently assigned double-blind treatment with orlistat (3 x 120 mg/day) or placebo for 6 months in conjunction with the hypocaloric diet. RESULTS: Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo. Total and low-density lipoprotein cholesterol decreased by 25-30 mg/dL vs. 10-15 mg/dL with placebo. Reduction of cholesterol with orlistat was significantly greater than anticipated from weight loss alone. In patients with cardiovascular risk factors entering the study with lower cholesterol values orlistat was also superior to placebo. On the contrary, reduction of cholesterol concentrations never exceeded 20%. CONCLUSION: Orlistat has a cholesterol lowering efficacy independent of its weight reducing effect. Because of the limited therapeutic effectiveness, patients at high cardiovascular risk should receive rather early additional cholesterol lowering medication during weight loss programmes.

Adolescent↗

[Statins-a panacea?].

Statins have proven their therapeutical value for a wide range of patients with coronary heart disease. The average reduction of the relative risk for cardiovascular events is 23%. This remains true even in the light of ALLHAT, which had failed to show a significant reduction in mortality in the statin subgroup, yet its significance suffered from an insufficient difference in the reduction of plasma lipids in the intervention group as compared to usual care. On the other hand, ASCOT and PROSPER have demonstrated the efficacy of statins in normolipemic hypertensives and elderly patients. The safety of statin therapy can be considered as good; for example the Prospective Pravastatin Pooling Project with 19,592 patients found a rate of unexpected events equal to placebo.

Aged↗

Hydration pressure and phase transitions of phospholipids. I. Piezotropic approach.

Dehydration reduces the main phase transition pressure of phospholipids. An analysis based on the Gibbs-Duhem equation shows how the shift of the transition pressure is correlated to the hydration pressure. By using Fourier transform infrared (FT-IR) spectroscopy we determined the hydration-dependent phase transition pressure. The application of our new approach gives hydration pressure values which agree with the values obtained with the osmotic stress method.

Hydrophobic and Hydrophilic Interactions↗

Hydration pressure and phase transitions of phospholipids. II. Thermotropic approach.

It is widely known that dehydration increases the main phase transition temperature of phospholipids. A mathematical analysis now shows that hydration pressure can be calculated by the dehydration-induced shift of the phase transition temperature. The hydration-dependent piezotropic and thermotropic phase transitions were determined by using calorimetry and FT-IR spectroscopy, and the application of our approach gives hydration pressure parameters that agree very well with the values obtained with the osmotic stress method.

Calorimetry, Differential Scanning↗

Measuring the quantum state of a large angular momentum.

We demonstrate a general method to measure the quantum state of an angular momentum of arbitrary magnitude. The (2F+1)x(2F+1) density matrix is completely determined from a set of Stern-Gerlach measurements with (4F+1) different orientations of the quantization axis. We implement the protocol for laser cooled Cesium atoms in the 6S(1/2)(F = 4) hyperfine ground state and apply it to a variety of test states prepared by optical pumping and Larmor precession. A comparison of input and measured states shows typical reconstruction fidelities F >/~0.95.

Journal Article↗

Contents of trans-fatty acids in human substernal adipose tissue and plasma lipids: relation to angiographically documented coronary heart disease.

The contents of trans-fatty acid (TFA) isomers of human substernal adipose tissue and plasma lipids (cholesterol esters, triacylglycerols, phospholipids), obtained from patients with angiographically documented coronary heart disease (CHD group; n = 24) and from controls (excluded CHD; n = 25), were determined by capillary gas chromatography. No significant difference (P <0.05) could be observed between cases (2.59 +/- 33%) and controls (2.79 +/- 0.76%) with regard to adipose tissue total TFA contents (expressed as proportion of all identified fatty acid methyl esters). The total adipose tissue TFA content reflected the dietary TFA intake, which was estimated by dietary questionnaires. Both groups showed significant differences in several isomeric plasma lipid TFA. Cases generally had a tendency to lower individual TFA contents.

Adipose Tissue↗

X-Ray Diffraction Study of the Lamellar-Hexagonal Phase Transition in Phospholipid/Surfactant Mixtures.

The lamellar-to-hexagonal phase transition of a phospholipid/ surfactant mixed system of 1-palmitoyl-2-oleoyl-sn-glycero-3phosphocholine (POPC) and oligo(ethylene oxide)dodecyl ethers of type C12H25O(CH2CH2O)2H(C12E2) in molar surfactant/phospholipid ratio (RS/L) of 2 at low hydration driven by temperature has been studied by X-ray diffraction. The Lbeta-HII phase transition is a reversible two-state process showing hysteresis at fast temperature scan rates. The obtained hexagonal phase exhibits a temperature dependent structural change. The numbers of bound water molecules per composite particle (WS+L) absorbed in the lamellar and hexagonal phases are nearly the same, changing from WS+L = 5.0 to 4.7 during the phase transition. The fluidity of the alkyl chains on increasing the temperature and the close packing of the hydrophilic molecular parts are the driving parameters of the lamellar-to-hexagonal transformation. Copyright 1998 Academic Press.

Journal Article↗

Effective treatment of lymphedema of the extremities.

OBJECTIVE: To define the immediate and long-term volumetric reduction following complete decongestive physiotherapy (CDP) for lymphedema. DESIGN: Prospective study of consecutively treated patients. SETTING: Freestanding outpatient referral centers. PATIENTS: Two hundred ninety-nine patients referred for evaluation of lymphedema of the upper (2% primary, 98% secondary) or lower (61.3% primary, 38.7% secondary) extremities were treated with CDP for an average duration of 15.7 days. Lymphedema reduction was measured following completion of treatment and at 6- and 12-month follow-up visits. INTERVENTION: Complete decongestive physiotherapy is a 2-phase noninvasive therapeutic regimen. The first phase consists of manual lymphatic massage, multilayered inelastic compression bandaging, remedial exercises, and meticulous skin care. Phase 2 focuses on self-care by means of daytime elastic sleeve or stocking compression, nocturnal wrapping, and continued exercises. MAIN OUTCOME MEASURES: Average limb volumes in milliliters were calculated prior to treatment, at the end of phase 1, and at 6- to 12-month intervals during phase 2 to assess percent volume reduction. RESULTS: Lymphedema reduction averaged 59.1% after upper-extremity CDP and 67.7% after lower-extremity treatment. With an average follow-up of 9 months, this improvement was maintained in compliant patients (86%) at 90% of the initial reduction for upper extremities and lower extremities. Noncompliant patients lost a part (33%) of their initial reduction. The incidence of infections decreased from 1.10 infections per patient per year to 0.65 infections per patient per year after a complete course of CDP. CONCLUSIONS: Complete decongestive physiotherapy is a highly effective treatment for both primary and secondary lymphedema. The initial reductions in volume achieved are maintained in the majority of the treated patients. These patients typically report a significant recovery from their previous cosmetic and functional impairments, and also from the psychosocial limitations they experienced from a physical stigma they felt was often trivialized by the medical and payor communities.

Bandages↗

Hydration of the dienic lipid dioctadecadienoylphosphatidylcholine in the lamellar phase--an infrared linear dichroism and x-ray study on headgroup orientation, water ordering, and bilayer dimensions.

In the phospholipid 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine (DODPC) in each of the fatty acid chains, a rigid diene group is inserted in a position near the polar/apolar boundary that is exceptionally sensitive for membrane stability. DODPC transforms upon gradual dehydration from the liquid-crystalline to a metastable gel state, which rearranges into two subgel phases at low and intermediate degrees of hydration. The molecular dimensions of the respective bilayers were determined by means of x-ray diffraction. Infrared linear dichroism of selected vibrations of the phosphate and trimethylammonium groups and of the nu13(OH) band of water adsorbed onto the lipid was used to study the molecular order in the polar part of the bilayers in macroscopically oriented samples. The dense packing of the tilted acyl chains in the subgel causes the in-plane orientation of the phosphatidylcholine headgroups with direct interactions between the phosphate and trimethylammonium groups, and a strong orientation of adsorbed water molecules. In the more disordered gel, the thickness of the polar part of the bilayer increases and the lateral interactions between the lipid headgroups weaken. The higher order in the headgroup region of the subgels correlates with shorter decay lengths of the repulsive forces acting between opposite membrane surfaces. This result can be understood if the work to dehydrate the lipid is determined to a certain degree by the work to break up the lipid-water interactions without compensation by adequate lipid-lipid contacts. Almost similar area compressibility moduli are found in the liquid-crystalline and solid phases. Obviously, the lipid avoids lateral stress by the structural rearrangement.

Biophysical Phenomena↗

[Economic aspects of drug therapy exemplified by pravastatin. A socioeconomic analysis of cholesterol synthase enzyme inhibition in coronary heart disease patients].

BACKGROUND: Decision makers in the field of health services are increasingly forced to identify and realise the grounds for spendings and savings. Therefore, preventive measures of cardiovascular diseases are becoming more and more scrutinized. The present analysis is answering the question: Is secondary preventive lipid-lowering therapy with a cholesterol-synthesis-enzyme-(CSE-)inhibitor in patients with manifest coronary heart disease cost-effective in comparison to other already proven medical interventions? METHODS: The cost-effectiveness-analysis with the endpoint costs per life years saved had been chosen as a form of evaluation. The study is a retrospective analysis. The clinical data have been taken from the already published double blinded, randomised, placebo controlled PLAC-I- and -II-studies as well as from the PLAC-Meta-Analysis. The cost estimate (costs of myocardial infarction, stroke and cost therapy with pravastatin) were based on the perspective of the German statutory sick funds. RESULTS: With the reduced probability of a fatal myocardial infarction or a stroke in the group treated with pravastatin there are cost offsets of DM 2,400. This figure is opposed to an additional expenditure of about DM 6,900, -for the CSE-inhibitor. The calculation of the effectiveness resulted in an additional life expectancy of 0.28 years in the pravastatin cohorts in comparison with the group treated with placebo over an observation period of 3 years. The costs per life year saved are approximately DM 16,000,-. CONCLUSION: The preventive use of pravastatin in patients with coronary heart disease can be estimated as cost-effective as compared with other medical interventions.

Anticholesteremic Agents↗

Characterisation of antibiotic moenomycin A interaction with phospholipid model membranes.

Using a combination of physico-chemical techniques (MAS NMR, DSC, freeze-fracture electron microscopy, molecular modelling) the antibiotic moenomycin A was found to be anchored by its hydrophobic chain into multilamellar POPC membranes. The lamellar phase structure of the modified membrane is retained, while moenomycin A in water at different concentrations does not form any other but isotropic phase structures. The mobility of POPC molecule segments is reduced with increasing moenomycin A concentrations. Freeze-fracture electron microscopy images show ripple like structures for low moenomycin A concentrations, which are rare for high concentrations. A sugar-group network of the antibiotic seems to cover the whole membrane surface for molar ratios moenomycin A/POPC of 1:2, which is supported by 13C-MAS (Magic Angle Spinning) 31P-NMR, and molecular modelling.

Bambermycins↗

Surface areas and packing constraints in POPC C (12)EO (n) membranes. A time-resolved fluorescence study.

The surface area occupied by nonionic detergents of the type C(12)EO(n) (n = 1-8) in POPC C (12)EO (n) mixed membranes was studied by means of time-resolved resonance energy transfer (RET) between the fluorescent probe molecules NBD-PE and rhodamine-PE. The area data were interpreted within the frame of Israelachvili's concept of packing constraints yielding the critical packing parameter, f, as a measure of the asymmetry of the molecular shape of the membrane constituents. The asymmetry of the molecular shape of the detergent increases with the ethylene oxide chain length and correlates with the potency of the detergent to solubilize the bilayers and the reduction of the DPH order parameter. For n = 1-3, the membrane surface was found to expand by 0.25-0.30 nm(2) per incorporated C(12)EO(n) molecule. This value corresponds to the cross section of one hydrocarbon chain in liquid-crystalline phases. On increasing n from n = 4 to n = 8 the net area per detergent molecule increases from 0.43 nm(2) to 1.16 nm(2). These surface requirements are consistent with a disordered, coiled conformation of the EO-chains hydrated with up to two water molecules per ethylene oxide unit. For n > 5 the limiting mole fraction of the bilayer saturation was deduced from the f-data in the two-component bilayer. DPH and NBD-PE fluorescence lifetime data are discussed to give an indication of the accessibility of the probe environment to water molecules.

Journal Article↗