Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction

BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.

Pelvic floor stimulation: what are the good vibrations?

OBJECTIVE: The aim of this study was to determine if two different whole body vibration, sinusoidal vibration (SV) and stochastic resonance vibration (SRV), using various intensities lead to a reactive activation of pelvic floor muscles. STUDY DESIGN: We compared the pelvic floor muscle response of a healthy control group with that of a post partum group with weakened pelvic floor contraction. Activation effects of stochastic resonance vibration and sinusoidal vibration with six increasing vibration intensities were investigated using pelvic floor EMG and compared to activity during rest and maximum voluntary contraction. RESULTS: Both whole body vibration systems were able to activate pelvic floor muscles significantly depending on vibration intensity. Generally, the SRV achieved a significantly higher activation than maximum voluntary contraction, especially in women post partum and using a frequency of 6-12 Hz. CONCLUSION: SRV, compared to SV, leads to higher pelvic floor muscle activation in subjects with weakened pelvic floor muscles and achieves higher pelvic floor activation than maximum voluntary contraction alone. Neurourol. Urodynam. 28:405-410, 2009. (c) 2009 Wiley-Liss, Inc.

The need for transparency and good practices in the qPCR literature

Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.

Good just isn't Good enough. Best System Probabilities and the Foundations of Statistical Mechanics

Statistical physicists assume a probability distribution over micro-states to explain thermodynamic behavior. The question of this paper is whether these probabilities are part of a best system and can thus be interpreted as Humean chances. I consider two strategies, viz. a globalist as suggested by Loewer, and a localist as advocated by Frigg and Hoefer. Both strategies fail because the system they are part of have rivals that are roughly equally good, while ontic probabilities should be part of a clearly winning system. I conclude with the diagnosis that well-defined micro-probabilities under-estimate the robust character of explanations in statistical physics.

More than just Good Luck. How to Explain the Success of Monte Carlo Simulations

Monte Carlo simulation is a powerful method in many natural and social sciences. But what sort of method is it? And where does its power come from? Are Monte Carlo simulations experiments, theories or something else? The aim of this talk is to answer these questions and to explain the power of Monte Carlo simulations. I provide a classification of Monte Carlo techniques and defend the claim that Monte Carlo simulation is a sort of inference.

How nice is good for patients and for therapy outcome? The role of confrontation in the process of psychotherapy

It is well established that the therapeutic relationship contributes about as much to therapy outcome as 'technical' intervention. Furthermore, it follows clear prescriptive concepts in the same manner as technical interventions do. 'Motive Oriented Therapeutic Relationship' is such a concept for establishing a solid basis for whatever therapeutic work the patients' problems require (Grawe, 1980, 1992; Caspar, 1996). Yet, the therapeutic relationship doesn't explain everything because other factors play a significant role too. Previous studies showed that outcome is clearly better when therapists achieved a generally high quality of a therapeutic relationship when they did not shy away from possibly threatening interventions such as confrontations. This ratio of a fruitful alliance and marginally present confrontations in the same session also showed significant correlations with patient's assessment of alliance and progress in therapy (Figlioli et al., 2009).Aim: The current state of research in the field does not give any answers to questions like how good and bad confrontations can be characterized or what role does the intensity, respectively frequency of confrontations play in the process of psychotherapy. Methods: A sample of 80 therapies of 3 sessions each representing either good or bad outcome was judged moment by moment by independent raters if and how therapists used confrontative interventions. Results: Preliminary analyses show that successful confrontations are explicitly uttered, short but intense, related to important patients goals in therapy and embedded in prior complementarity. Discussion: The results will be discussed in terms of their implications for the clinical daily work.

How nice is good for patients and for therapy outcome? The role of confrontation in the process of psychotherapy

It is well established that the therapeutic relationship contributes about as much to therapy outcome as ‘technical’ intervention. Furthermore, it follows clear prescriptive concepts in the same manner as technical interventions do. ‘Motive Oriented Therapeutic Relationship’ is such a concept for establishing a solid basis for whatever therapeutic work the patients’ problems require (Grawe, 1980, 1992; Caspar, 1996). Yet, the therapeutic relationship doesn’t explain everything because other factors play a significant role too. Previous studies showed that outcome is clearly better when therapists achieved a generally high quality of a therapeutic relationship when they did not shy away from possibly threatening interventions such as confrontations. This ratio of a fruitful alliance and marginally present confrontations in the same session also showed significant correlations with patient’s assessment of alliance and progress in therapy (Figlioli et al., 2009). These findings are also very much in line with Sachse’s metaphor of accumulating, but then also using ‘relationship credits’ and Farrelly’s ‘Provocative Therapy’ (1986), as well as the ‘Intensive Short-Term Dynamic Psychotherapy’ by Davanloo (1980).Aim: The current state of research in the field does not give any answers to questions like how good and bad confrontations can be characterized or what role does the intensity, respectively frequency of confrontations play in the process of psychotherapy.Methods: A sample of 80 therapies of 3 sessions each representing either good or bad outcome was judged moment by moment by independent raters if and how therapists used confrontative interventions. Results / Discussion: The results will be discussed in terms of their implications for the clinical daily work. Preliminary analyses show that successful confrontations are explicitly uttered, short but intense, related to important patients goals in therapy and embedded in prior complementarity.