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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Results of the "Health Program Hypertension" of the German Health Insurance (DKV)].

BACKGROUND AND OBJECTIVE: In 2003 the German Health Insurance (DKV: Deutsche Krankenversicherung) initiated a "Health Program Hypertension" for its insured persons with the aim of motivating patients to adopt the accepted general measures for blood pressure reduction and to self-monitor their blood pressure. PATIENTS AND METHODS: Participation in the program was voluntary and without charge. The interventional measures included regular contact by phone with trained medical personnel, personal consultations targeting general measures and self measurement of blood pressure. Each patient was given training material and a blood pressure monitor, and a risk profile was made for each patient. Regular reports were given to the patients and their physicians. RESULTS: The data of the first 1373 hypertensives who have been in the continuing program were analysed. The patients" average age was 61+/-9.9 years, 81% males. 94% of the participants reported taking antihypertensive medication. Initially 615 patients (44.8%) had an increased blood pressure on self-measurement ((3)135/85 mmHg). The blood pressure of these patients was significantly reduced, after an average of 16.3 months, from 145/91+/-12.7 mmHg to 135/84 +/-12.8 mmHg (p<0.001). A statistically significant weight reduction was achieved in 308 patients (22.4%) with a body mass index (BMI) of (3) 30 kg/m2, from 33.4 to 32.9 kg/m2 (p<0.001). Lipid metabolism, important life-style parameters (food and physical activity) and a knowledge of important laboratory tests (glucose and creatinine) also changed positively. Antihypertensive medication remained nearly unchanged during the period of observation. CONCLUSIONS: The patients participating in the Health Program Hypertension were already reasonably well controlled. The program achieved further lasting improvement of blood pressure. In addition the participants were motivated to adopt a more health-conscious life style. Training and care of the patients by a medical services centre would seem sensible and successful. But it remains a challenge, especially to reach poorly controlled hypertensives and to motivate them to an active participation in the program.

Antihypertensive Agents↗
PubMed2005

How septic is urosepsis? Clinical course of infected hydronephrosis and therapeutic strategies.

Despite rapid decompression of the upper urinary tract, some patients show signs of systemic inflammatory response syndrome (SIRS) or septic shock syndrome when infected hydronephrosis is diagnosed. Clinical and biological parameters were analyzed retrospectively in 189 patients diagnosed with hydronephrosis regarding disease severity as well as microbiological and antibiotic features. Fifty of the 189 patients had positive urine culture in the renal pelvis and were included in the study. Fifteen patients had to be placed in the intensive care unit and two patients developed severe septic signs. An initial body temperature above 38.5 degrees C (P=0.0004) and an elevated BMI (P=0.002) were the only parameters that indicated a higher risk of developing SIRS or sepsis. Typical biological parameters were not helpful in differentiating patients who will develop urosepsis. Further research is necessary to provide conclusive evidence of the value of other early prognostic markers in patients with infected hydronephrosis.

Aged↗
PubMed2005

Field theoretic study of bilayer membrane fusion: II. Mechanism of a stalk-hole complex.

We use self-consistent field theory to determine structural and energetic properties of intermediates and transition states involved in bilayer membrane fusion. In particular, we extend our original calculations from those of the standard hemifusion mechanism, which was studied in detail in the first article of this series, to consider a possible alternative to it. This mechanism involves non-axial stalk expansion, in contrast to the axially symmetric evolution postulated in the classical mechanism. Elongation of the initial stalk facilitates the nucleation of holes and leads to destabilization of the fusing membranes via the formation of a stalk-hole complex. We study properties of this complex in detail, and show how transient leakage during fusion, previously predicted and recently observed in experiment, should vary with lipid architecture and tension. We also show that the barrier to fusion in the alternative mechanism is lower than that of the standard mechanism by a few k(B)T over most of the relevant region of system parameters, so that this alternative mechanism is a viable alternative to the standard pathway. We emphasize that any mechanism, such as this alternative one, which affects, even modestly, the line tension of a hole in a membrane, affects greatly the ability of that membrane to undergo fusion.

Biophysics↗
PubMed2005

TAp73/Delta Np73 influences apoptotic response, chemosensitivity and prognosis in hepatocellular carcinoma.

We investigated the mechanisms by which TAp73 beta and dominant-negative p73 (Delta Np73) regulate apoptosis. TAp73 beta transactivated the CD95 gene via the p53-binding site in the first intron. In addition, TAp73 beta induced expression of proapoptotic Bcl-2 family members and led to apoptosis via the mitochondrial pathway. Endogenous TAp73 was upregulated in response to DNA damage by chemotherapeutic drugs. On the contrary, DeltaNp73 conferred resistance to chemotherapy. Inhibition of CD95 gene transactivation was one mechanism by which DeltaNp73 functionally inactivated the tumor suppressor action of p53 and TAp73 beta. Concomitantly, DeltaNp73 inhibited apoptosis emanating from mitochondria. Thus, DeltaNp73 expression in tumors selects against both the death receptor and the mitochondrial apoptosis activity of TAp73 beta. The importance of these data is evidenced by our finding that upregulation of DeltaNp73 in hepatocellular carcinoma patients correlates with reduced survival. Our data indicate that Delta Np73 is an important gene in hepatocarcinogenesis and a relevant prognostic factor.

Apoptosis↗
PubMed2005

Phase transitions in nanosystems caused by interface motion: the Ising bipyramid with competing surface fields.

The phase behavior of a large but finite Ising ferromagnet in the presence of competing surface magnetic fields +/-H(s) is studied by Monte Carlo simulations and by phenomenological theory. Specifically, the geometry of a double pyramid of height 2L is considered, such that the surface field is positive on the four upper triangular surfaces of the bipyramid and negative on the lower ones. It is shown that the total spontaneous magnetization vanishes (for L --> infinity) at the temperature Tf(H), related to the "filling transition" of a semi-infinite pyramid, which can be well below the critical temperature of the bulk. The discontinuous vanishing of the magnetization is accompanied by a susceptibility that diverges with a Curie-Weiss power law, when the transition is approached from either side. A Landau theory with size-dependent critical amplitudes is proposed to explain these observations, and confirmed by finite size scaling analysis of the simulation results. The extension of these results to other nanosystems (gas-liquid systems, binary mixtures, etc.) is briefly discussed.

Journal Article↗
PubMed2005

Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis.

BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Administration, Rectal↗
PubMed2005

Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis.

OBJECTIVES: Pharmacokinetic (PK)/pharmacodynamic (PD) models have become increasingly important in optimizing antimicrobial therapy. This approach is highly recommended by regulatory authorities intending to force the evaluation of antimicrobial action at the site of infection. METHODS: Clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus with MICs of 4, 8 and 16 mg/L for piperacillin were used in an in vivo PK/in vitro PD model. Bacteria were exposed in vitro to the concentration-versus-time profiles of piperacillin in plasma and subcutaneous adipose tissue measured in vivo in septic patients. Samples were withdrawn at defined intervals and the numbers of bacteria per mL were counted and plotted against time. RESULTS: Piperacillin levels determined in plasma were able to effectively inhibit bacterial growth of all bacterial strains used in the present study (MIC ranged from 4-16 mg/L). In contrast, concentration-versus-time profiles of subcutaneous adipose tissue were effective in killing isolates with MICs of 4 and 8 mg/L only, while bacterial growth of S. aureus and P. aeruginosa with MICs of 16 mg/L was not inhibited. CONCLUSIONS: Bacteria with MICs < 16 mg/L were effectively inhibited in subcutaneous adipose tissue in patients with sepsis. The prediction of microbiological outcome based on concentrations of piperacillin in plasma resulted in a marked overestimation of antimicrobial activity at the site of infection.

Aged↗
PubMed2005

Suppression of capillary wave broadening of interfaces in binary alloys due to elastic interactions.

By Monte Carlo simulations in the constant-temperature--constant-pressure ensemble a planar interface between unmixed A-rich and B-rich phases of a binary (A, B) alloy on a compressible diamond lattice is studied. No significant capillary wave broadening of the concentration profile across the interface is observed, unlike lattice models of incompressible mixtures and fluids. The distortion of the lattice structure across the interface is studied.

Journal Article↗
PubMed2005

Bone-implant interface shear modulus and ultimate stress in a transcortical rabbit model of open-pore Ti6Al4V implants.

This experimental study on laser-textured implants aimed to evaluate periimplant bone elasticity and ultimate stress of the bone-implant interface in a rabbit femur model. After randomization, two cylindrical Ti6Al4V samples (3.5 mm wide, 5.5 mm long) were transcortically implanted in each femur of 15 female New Zealand White Rabbits. Polished implants had been laser-textured with 100, 200, and 300 microm diameter pores, and another corundum blasted implant was additionally textured with 200 microm pores. Twelve weeks into the experiment, a modified push-out test was performed. The median shear modulus indicating the elasticity of the periimplant bone was 41.12 MPa for the proximal implant location and 25.38 MPa for the distal, without evidence for significant differences between implant types. Taking into account the median ultimate shear stress for 200 microm implants with and without corundum blasting, no significant difference could be demonstrated. However, for blasted 200 microm implants a statistically significant (p<0.025) relative gain in ultimate shear stress of 41% and 17% was proven in comparison with 100 and 300 microm implants, respectively. Non-blasted 200 microm implants reached 48% relative gain in respect of 100 microm samples.

Alloys↗
PubMed2005

Low-dose prednisolone has a CD4-stabilizing effect in pre-treated HIV-patients during structured therapy interruptions (STI).

BACKGROUND: A favorable development of CD4+ T cells was firstly noticed in therapy-naive HIV-patients without antiretroviral therapy (ART) taking 5 mg prednisolone daily. This observation led to the prescription of prednisolone during structured therapy interruptions (STI). OBJECTIVE: To evaluate the effect of low dose prednisolone on pre-treated patients during STI. METHODS: A retrospective analysis including all pre-treated patients with prednisolone therapy for > or =6 months during STI has been conducted. The patients with prednisolone onset right at the beginning of STI (n = 95) were compared with all patients without prednisolone therapy during their first 6 months of STI (n = 49). Patients with prednisolone were divided into two subgroups: the ongoing STI-group and the patients with ART-restart. Additionally, the development of all 33 patients from the control group having started prednisolone later during STI was documented. Irrespective of the time of initiation of prednisolone therapy during STI, the development of CD4+ T cells in all patients with prednisolone for >12 months during STI was analyzed (n = 108). RESULTS: The mean daily CD4+ T cell decrease during STI was significantly less pronounced in the prednisolone-group (-0.50 vs. -0.74 cells/day; p = 0.0361). The daily CD4+ T cell decline of the 33 patients from the control subgroup including patients with a later onset of prednisolone therapy was only -0.11 during a mean time of 715 days under prednisolone. The CD4+ T cell count of the STI-patients treated with prednisolone for >12 months (n = 108; mean: 837 days +/- 64.6 (366-1,756 days)) decreased from 677/microl to 504/microl. - 51 of 81 patients (63%) included in 2-year-analysis showed stable CD4+ T cell counts (mean daily CD4+ T cell decrease: 0.08) and continued ART interruption. CONCLUSION: This retrospective evaluation provides evidence that low dose corticosteroids are associated with less decrease of CD4+ T cell count in pre-treated HIV patients resulting in prolongation of the potential time of structured treatment interruptions for many HIV patients.

AIDS-Related Opportunistic Infections↗
PubMed2005

[Integrated skills laboratory concept for undergraduate training in internal medicine].

BACKGROUND AND OBJECTIVE: An amendment to the German medical curriculum in April 2002 will place basic practical skills at the centre of medical training. We report here on the implementation and evaluation of an obligatory, tutor-guided, and integrated skills laboratory concept in the field of internal medicine. METHODS: To test the effectiveness of a skills laboratory training on OSCE performance a pilot study was carried out. The experimental group, of 77 students, participated in seven sessions of communication training, skills laboratory training, and bedside teaching, each lasting one and a half hours. The control group of 66 students had as many sessions but was only offered bedside-teaching. The evaluation of acceptance of skills' training as well as the related increase in individual competence is on-going (summer term 2004: n = 176 students). RESULTS: The integrated skills laboratory concept was rated at 3.5 (SD = 1.2) on a 5-point scale and was acknowledged as practice-oriented (M = 4.2; SD = 1.0) and relevant for doctors' everyday lives (M = 3.6; SD = 1.1). Increased levels of competence according to individual self-evaluations proved to be highly significant (p<.001), and results of the pilot study showed that the experimental group had a significantly better OSCE performance than the control group (p<.001). CONCLUSION: This pilot study shows that curriculum changes promoting basic clinical skills are effective and lead to an improved practical education of tomorrow's physicians. The integrated skills laboratory concept is well accepted and leads to a relevant increase in competence in the practice of internal medical. The presented skills laboratory concept in internal medicine is proving to be a viable and efficient learning tool.

Adult↗
PubMed2005

Dense orientationally ordered states of a single semiflexible macromolecule: an expanded ensemble Monte Carlo simulation.

Using a coarse-grained model we perform a Monte Carlo simulation of the state behavior of an individual semiflexible macromolecule. Chains consisting of N = 256 and 512 monomer units have been investigated. A recently proposed enhanced sampling Monte Carlo technique for the bond fluctuation model in an expanded ensemble in four-dimensional coordinate space was applied. The algorithm allows one to accelerate the sampling of statistically independent three-dimensional conformations in a dense globular state. We found that the temperature of the intraglobular liquid-solid transition decreases with increasing chain stiffness. We have investigated the possible intraglobular orientationally ordered (i.e., liquid-crystalline) structures and obtained a diagram of states for chains consisting of N = 256 monomer units. This diagram contains regions of stability of coil, two spherical globules (liquid and solid), and rod-like globule conformations. Transitions between the globular states are rounded first-order ones since the states of liquid, solid, and cylinder-like globules do have different internal symmetry.

Journal Article↗
PubMed2005

[New drugs--hope for salvage patients?].

New and potent drugs are urgently needed for the salvage therapy of HIV-infected patients. The protease inhibitors Tipranavir and TMC114, which have high potency against multidrug-resistant viral strains, are the most promising drugs for the near future. How important they will be in salvage therapy cannot be predicted at this time. New points of attack in the viral replication cycle have been defined. Substances belonging to the groups of integrase and maturation inhibitors are in the early stages of clinical development.

Anti-HIV Agents↗
PubMed2005

First-order interface localization-delocalization transition in thin Ising films using Wang-Landau sampling.

Using extensive Monte Carlo simulations, we study the interface localization-delocalization transition of a thin Ising film with antisymmetric competing walls for a set of parameters where the transition is strongly first order. This is achieved by estimating the density of states (DOS) of the model by means of Wang-Landau sampling (WLS) in the space of energy, using both single-spin-flip as well as N-fold way updates. From the DOS we calculate canonical averages related to the configurational energy, like the internal energy and the specific heat, as well as the free energy and the entropy. By sampling micro-canonical averages during simulations we also compute thermodynamic quantities related to magnetization like the reduced fourth-order cumulant of the order parameter. We estimate the triple temperatures of infinitely large systems for three different film thicknesses via finite size scaling of the positions of the maxima of the specific heat, the minima of the cumulant, and the equal weight criterion for the energy probability distribution. The wetting temperature of the semi-infinite system is computed with help of the Young equation. In the limit of large film thicknesses the triple temperatures are seen to converge toward the wetting temperature of the corresponding semi-infinite Ising model in accordance with standard capillary wave theory. We discuss the slowing down of WLS in energy space as observed for the larger film thicknesses and lateral linear dimensions. In the case of WLS in the space of total magnetization we find evidence that the slowing down is reduced and can be attributed to persisting free energy barriers due to shape transitions.

Journal Article↗
PubMed2005

Unmixing of polymer blends confined in ultrathin films: crossover between two-dimensional and three-dimensional behavior.

The interplay between chain conformations and phase separation in binary symmetric polymer mixtures confined into thin films by "neutral" hard walls (i.e., walls that do not preferentially attract or repel one of the two components of the mixture) is studied by Monte Carlo simulations. Using the bond fluctuation model on a simple cubic lattice in the semi grand canonical ensemble, we locate the critical temperature of demixing via finite size scaling methods for a wide range of chain lengths (16 </= N </= 256 effective monomers per chain) and film thicknesses (2 </= D </= 19 lattice spacings). Simultaneously, we investigate the geometrical structure of the chains, showing that despite using melt densities there are pronounced "correlation hole effects", in particular for the smaller values of D. Also the components of the radius of gyration and end-to-end distance parallel and perpendicular to the confining walls are analyzed and their scaling behavior is studied. Evidence is presented that for strictly two-dimensional polymers (as occur for D = 2) the average number of intermolecular contacts scales with chain length N as z(c) proportional, variant N(-3/8) and therefore the critical temperature scales as T(c) proportional, variant N(5/8), whereas for values of D that exceed the excluded volume screening length, z(c) remains nonzero for N --> infinity, and hence T(c) proportional, variant N. However, strong deviations from the Flory-Huggins theory occur as long as the unperturbed chain dimension exceeds D, and the critical behavior falls in the universality class of the two-dimensional Ising model for any finite value of D.

Journal Article↗
PubMed2005

Low dose prednisolone reduces CD4+ T cell loss in therapy-naive HIV-patients without antiretroviral therapy.

BACKGROUND: A favorable development of CD4+ T cells was noticed in therapy-naive HIV-patients without antiretroviral therapy (ART) taking 5 mg prednisolone daily. Based on these encouraging observations, prednisolone therapy in further HIV-patients without antiretroviral therapy was initiated. OBJECTIVE: To evaluate the effect of low dose prednisolone on therapy-naive HIV patients without antiretroviral therapy. METHODS: A retrospective analysis has been conducted comparing the development of CD4+ T cells, viral load and clinical outcome in all therapy-naive HIV-patients with (n = 65; CD4 > or =300/microl) or without (n = 136; CD4 > or =300/microl) prednisolone treatment for > or =6 months. RESULTS: After 3 years, therapy-naive patients on prednisolone therapy showed a CD4+ T cell increase of +50.1/microl whereas in the untreated group a decrease of -186.1/microl (p = 0.0021) was noted. After 12 months, nearly twice as much untreated patients experienced a first-time CD4+ T cell loss of >100/microl or initiation of HAART due to clinical development compared to prednisolone-treated patients (64.1% vs. 35.0%). CD4+ T cell increase was associated with viral load at baseline: Patients with lower viral loads at baseline (<30,000 copies/ml) showed a favorable development with statistically significant less drop-outs (defined as HAART-onset and/or prednisolone discontinuation for the prednisolone group) than patients with higher viral loads at baseline in the first 3 years in the prednisolone group. - CONCLUSION: Low dose prednisolone seems to be associated with a stabilization of CD4+ T cell count in therapy-naive HIV patients resulting in a pronounced prolongation of the potential time without HAART for many HIV patients.

CD4 Lymphocyte Count↗
PubMed2005

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers.

OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. METHODS: Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations. Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 microg/ml and 0.341 microg/ml. A CSF-plasma partition coefficient of 0.002 and a k(e0) value of 0.059 h(-1) were estimated by means of population modeling. CONCLUSION: In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations experimentally proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient.

Adult↗