The observed 20% reduction of mortality, 60% reduction of stroke and 20% reduction of dialysis were partly neutralized by the adjusting methods and demand, at least, larger datasets to obtain statistical significance. Subdatasets with fewer patients but higher risk identified risk-reducing effects for stroke. Hospital stay was shortened by the OPCAB approach. The interactions between risk, number of patients and the risk-reducing effect are the cornerstones of evidence generation for the OPCAB approach. These results were obtained through a very strict reengineering and cannot be extended to all OPCAB programs.

1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH) has been attributed a cardiovascular effect, inducing an increase in blood pressure and heart rate. Although still controversial, this effect, based on pharmacological blockade experiments, is supposed to be mediated through sympathetic activation. 2. The aims of the present study were to identify the N-terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence blood pressure and heart rate and to investigate the real-time changes in baroreflex sensitivity and in sympathetic and vagal modulation underlying cardiovascular effects in conscious rats without the use of pharmacological blockade. 3. Intracerebroventricular administration of different melanocortins and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol onwards, with only a small initial bradycardic response with the highest dose. 4. Coinciding with this pressor response, an elicitation of the low-frequency (LF) component was observed in spectral analysis of both blood pressure variability (BPV) and heart rate variability (HRV), followed by the high-frequency (HF) component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent pressor and cardioaccelerator response with very rapid onset with concentrations from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex sensitivity and simultaneously increased both components of BPV, with a radical reduction of the LF component and a preserved vagal HF component in HRV. 7. Of all the intravenously administered melanocortins, only gamma(2)-MSH was active. The central effect is likely to depend on an increase of (alpha-)sympathetic outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a baroreceptor reflex-blocking agent, being compatible with a role in the acute stress response.

The multimodal OPCAB re-training resulted in a substantial increase of the application, concomitant with a decrease in conversion. The positive impact on attitude and complexity score, at exit, was somewhat reduced in the following clinical confrontation.

A pituitary cell population of 14-day-old female rats, containing lactotropes and somatotropes but deprived of gonadotropes, was prepared by unit gravity sedimentation through a serum albumin gradient and allowed to reaggregate either as such or after mixing this population with cells of the gonadotropic αT3-1 cell line. In a perifusion system gonadotropin-releasing hormone (GnRH) had no effect on prolactin (PRL) and growth hormone (GH) release in the former aggregates but stimulated PRL release in the latter. In the αT3-l cell-containing aggregates GnRH showed a biphasic effect on GH release: inhibition during exposure to GnRH followed by a rebound secretion upon removal of the peptide. The aggregation capacity of αT3-l cells with the normal pituitary cells was demonstrated by using an αT3-l cell clone stably transfected with the reporter gene β-galactosidase. Perifusion of the gonado-trope-deprived aggregates with medium conditioned by αT3-1 cell provoked a rapid stimulation of PRL release and a biphasic effect on GH release. Medium conditioned by the cortico-tropic cell line AtT20 also stimulated PRL release but had no concomitant effect on GH release. Medium conditioned by αT3-l cells, when added for 40 h to aggregates of 14-day-old rat pituitary, provoked an increase in the number of ³H-thymidine (³H-T)-labelled lactotropes and a decreased in the number of ³H-T-labelled somatotropes. The conditioned medium was concentrated on Sep-Pak C18 and ultrafiltrated through an Amicon membrane with 3-kD molecular weight cut-off and the retained molecules separated by reversed-phase HPLC. The material stimulating ³H-T labelling of lactotropes eluted from the column with a different retention time than material inhibiting ³H-T labelling of somatotropes, suggesting that the effect on lactotropes is mediated by (a) molecule(s) different from that affecting somatotropes. The effects of αT3-l cells and their secretion products on lactotropes and somatotropes were comparable to those we previously observed using enriched populations of normal gonadotropes. The HPLC elution profiles of the substances affecting ³H-T incorporation as well as the specificity of these effects were also similar to that of the substances isolated previously from gonadotrope-conditioned medium. The present data, therefore, support previous conclusions on the paracrine control of the lactotrope/somatotrope lineage by the gonadotropes. Further purification and chemical characterization of the growth factors with selective action on lactotropes and somatotropes may lead to a better understanding of the development of the latter lineage.

No abstract