Ergebnisse der Herzinfarktregister in Chemnitz 1974–1999

Myocardial infarction has great importance for the populations in industrial countries because of the high morbidity and mortality rates. For research of the epidemiological trends in the 1970s and especially in the 1980s, the World Health Organization (WHO) began registering myocardial infarction throughout the world. The most important aspect was the WHO Monitoring of Trends and Determinants of Cardiovascular Diseases (MONICA) project. From 1974 to 1994 and in 1999 in Chemnitz, Germany, data from patients with acute myocardial infarction were collected for the myocardial infarction register. Despite changes in the event rates from year to year, no decrease in the number of myocardial infarctions in the German population aged 25–64 years was detected, contrary to the trend in the Western industrial states in the period from 1984 to 1994. The event rates in men were significantly higher than in women. In 1999, a significant decrease in the event rates in men and women was found. This may be explained by an incomplete registration of patients with myocardial infarction in 1999 because of the change in the structure of the Public Health System. The highest 28-day fatality rates in men were detected in 1989 and 1990. In women with classic myocardial infarction, a decrease in the 28-day fatality rates after 1993 was recorded, reaching lower rates than those of men. Despite methodological problems, the myocardial infarction register can contribute to a comparison of the morbidity, mortality and case fatality rates of myocardial infarction for a longer period.     

Pharmacokinetics,biocompatibility and bioavailability of a controlled release monoclonal antibody formulation

The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (T_max) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery.     

Short-term preoperative supplementation of an immunoenriched diet does not improve clinical outcome in well-nourished patients undergoing abdominal cancer surgery

ObjectiveA recent study suggested that the anti-inflammatory effect of immunonutrition starts after only two d. We therefore investigated the effect of an immunoenriched oral diet administered for three d preoperatively.MethodsIn this prospective, randomized, double-blind, placebo-controlled study, well-nourished patients (Nutrition Risk Screening 2002 <3) with gastrointestinal cancer who were scheduled for major elective abdominal cancer surgery were randomly assigned to either 750 mL of an immunoenriched formula (IEF group) or 750 mL of an isocaloric, isonitrogenous placebo diet (Con group) for 3 consecutive d preoperatively.ResultsA total of 108 patients (IEF group: n = 55; Con group: n = 53) were randomized. The two groups were comparable for all baseline and surgical characteristics. The overall mortality was 2.8% and not significantly different between the two groups (IEF group: 3.6% vs. Con group: 1.9%, P = 1.00). Intention-to-treat analysis showed no difference for the incidence of postoperative overall (IEF group: 29% vs. Con group: 30%; P = 1.00) and infectious (IEF group: 15% vs. Con group: 17%; P = 0.79) complications. Length of hospital stay was 12 ± 4.9 d in the IEF group and 11.6 ± 5.3 d in the Con group (P = 0.68).ConclusionsPreoperative oral supplementation with an immunoenriched diet for 3 d preoperatively did not improve postoperative outcome compared with the placebo in well-nourished patients with elective gastrointestinal cancer surgery.     

Altern und Wertewandel

The process of ageing and the relevant scientific disciplines are influenced by societal values und priorities. Values are the object of scientific and public reflection mainly in times of strong changes and obvious conflicts. The article discusses fundamental social and cultural changes from collective integration to personal freedom and autonomy. The focus of this paper is directed towards the impact of the consequences and contradictions of such cultural changes on the process of ageing and of ageing research.     

Role of a second stage partogram in predicting the outcome of normal labour

Background: Management of the second stage of labour is dictated by arbitrary time limits rather than true measures of progress. No partogram is available for second stage of labour.
Objectives: To evaluate a partogram designed for use for the second stage of labour.
Methods: This prospective cross-sectional analytical study included low-risk pregnant women with singleton fetuses with vertex presentations at term. From onset of the second stage, vaginal examinations were performed every 30 min until delivery. A scoring system developed by Sizer et al . was used based on station and position of fetal head. Scores were plotted on a second stage partogram and used to predict labour outcomes, such as duration of second stage and mode of delivery.
Results: Of 79 women examined, 73 had spontaneous vaginal delivery. Of the remaining six, four required oxytocin infusion and other two required vacuum extraction. The median durations of the second stage of labour for primigravidas ( n  = 34) and multigravidas ( n  = 45) were 35 and 25 min, respectively. The median Sizer's partogram score at the onset of second stage was 4. Multiple regression analysis showed that the partogram score ( r ² = 0.27) and gravidity ( r ² = 0.10) were independent predictors of duration of the second stage. There was a significant association between second stage progress plotted to the right of the partogram line and non-spontaneous delivery ( P =  0.01).
Conclusion: The second stage partogram score at onset can predict the duration of second stage. Poor progress plotted on the partogram is associated with non-spontaneous delivery.     

Experimental test of a predicted dynamics–structure–thermodynamics connection in molecularly complex glass-forming liquids

Understanding in a unified manner the generic and chemically specific aspects of activated dynamics in diverse glass-forming liquids over 14 or more decades in time is a grand challenge in condensed matter physics, physical chemistry, and materials science and engineering. Large families of conceptually distinct models have postulated a causal connection with qualitatively different “order parameters” including various measures of structure, free volume, thermodynamic properties, short or intermediate time dynamics, and mechanical properties. Construction of a predictive theory that covers both the noncooperative and cooperative activated relaxation regimes remains elusive. Here, we test using solely experimental data a recent microscopic dynamical theory prediction that although activated relaxation is a spatially coupled local–nonlocal event with barriers quantified by local pair structure, it can also be understood based on the dimensionless compressibility via an equilibrium statistical mechanics connection between thermodynamics and structure. This prediction is found to be consistent with observations on diverse fragile molecular liquids under isobaric and isochoric conditions and provides a different conceptual view of the global relaxation map. As a corollary, a theoretical basis is established for the structural relaxation time scale growing exponentially with inverse temperature to a high power, consistent with experiments in the deeply supercooled regime. A criterion for the irrelevance of collective elasticity effects is deduced and shown to be consistent with viscous flow in low-fragility inorganic network-forming melts. Finally, implications for relaxation in the equilibrated deep glass state are briefly considered.

An enormous number of seemingly orthogonal proposals exist for a fundamental connection between a (typically scalar) structural or excess (configurational) thermodynamic quantity and activated relaxation in supercooled liquids (1–12). High chemical complexity for fragile glass formers which exhibit strongly non-Arrhenius relaxation greatly complicates the formulation of predictive theories. A common generic view (1, 3, 8) is that the structural or alpha relaxation time (and viscosity, inverse diffusivity) evolves with cooling as shown in Fig. 1A. Different dynamical mechanisms in the high-, intermediate-, and low-temperature regimes are often envisioned: noncooperative Arrhenius (∼1 ps to 100 ps), critical power law (∼0.1 ns to 100 ns), and cooperative non-Arrhenius (∼0.1 μs to 100 s or beyond), respectively. Typically a causal connection is postulated between the logarithm of the alpha time (an effective barrier in thermal energy units) and a specific “order parameter”: 1) in the structural class (6, 7, 13–17), the intensity of the cage peak of the structure factor S(k), local aspect(s) of the radial distribution function g(r), or specific packing motifs; 2) in the thermodynamics class, various measures of free volume (18, 19), excess entropy (20), configurational entropy (21–25), internal energy and enthalpy (26), or with some arguing for an equilibrium phase transition at an inaccessibly low (high) temperature (density) (23, 27–29); 3) in the short time class, the high-frequency shear modulus (2, 30–32), Debye–Waller factor (33), or amplitude of special vibrational modes (33–35); and 4) in the intermediate time class, the concentration of dilute mobile excitations [e.g., strings (36, 37) or facilitating defects (38)]. Many of the proposed order parameters are hard or impossible to uniquely define and/or experimentally measure. The diverse models often claim to capture relaxation data over limited time windows typically based on fitting but usually fail at low and/or high enough temperature (5).Open in a separate windowFig. 1.Global relaxation map and theoretical picture and key predictions. (A) Three-regime relaxation map (curves) for the alpha time with Arrhenius and strongly non-Arrhenius behaviors separated by a crossover regime perhaps of a critical power law (6) form. The proposed two-regime scenario of ECNLE theory (39–42) is based solely on noncooperative and cooperative activated dynamics (slightly overlapping orange and green regions) with the inverse dimensionless compressibility (S0−1) as the relevant thermodynamic quantity. The approximately five to six decade range that simulations can probe is indicated. (B) Dynamic free energy for a metastable hard sphere (diameter σ) fluid (42) as a function of particle displacement at a high packing fraction of ϕ = 0.58. Relevant length and energy scales are indicated. (Inset) Schematic of the core physical idea for the alpha relaxation: hopping on the cage scale coupled with a collective elastic displacement of all particles outside the cage. (C) Main: local cage barrier as a function of inverse dimensionless compressibility for 0.44<ϕ <0.61 corresponding to a 16 decade increase of the alpha time (39, 41, 42). The metastable regime begins at ϕ ∼ 0.5 where the total barrier is ∼1.5 k_BT. (Inset) Total barrier as a function of S0−3 normalized by its ϕ = 0.5 value. The elastic barrier is 1 k_BT at ϕ ∼ 0.55. Packing fractions are given along the top x-axis.Here we present, using only experimental data, a test of a relationship between activated relaxation, local pair structure, and a specific thermodynamic property predicted by the Elastically Collective Nonlinear Langevin Equation (ECNLE) theory (39–41). The results provide support for the following: 1) the coupled local–nonlocal nature of relaxation deeply connected with collective elasticity, 2) the dimensionless amplitude of thermal density fluctuations, S₀, as the relevant (nonexcess) thermodynamic property, 3) a roadmap for organizing relaxation data in S₀, not in temperature, space, 4) irrelevance of collective elasticity as the origin for the crossover from fragile to strong glass formers, and 5) an explicit demonstration that a dynamics–thermodynamics correlation can be a noncausal consequence of the causal relation between local pair structure and S₀.