Ziel: Mit der integrierten Versorgung (IV) hat der Gesetzgeber die Möglichkeit einer sektorenübergreifenden Leistungs- und Vergütungsform eröffnet (§ 140 a–d SGB V) und damit die Voraussetzungen für eine engere Zusammenarbeit zwischen den Leistungserbringern der Gesundheitsversorgung deutlich verbessert. Patienten vor einem Hüft- oder Kniegelenkersatz erwarten von einer solch verbesserten Zusammenarbeit zwischen Akut- und Rehabilitationsklinik einen höheren Nutzen. Bislang gibt es jedoch keine Studien, die die erwarteten Effekte auf die funktionellen Behandlungsergebnisse überprüft haben. Ziel unserer Studie war daher die Evaluation der Wirksamkeit eines endoprothetischen IV-Modells im Vergleich zur herkömmlichen Regelversorgung.

AIMS:In Germany, introduction of the law on Integrated Health Care (IC) (section sign 140a-d SGB V) opened up the possibility of cross-sectoral health care settings and new forms of remuneration, and improved the conditions for a closer cooperation between health care providers. However, cross-institutional and interdisciplinary work contexts demand new organizational structures in order to assure the coordination of different competences, resources and interests. This study aims at identifying factors of successful integrated care settings for total hip and knee arthroplasty. Using the example of an integrated care setting between an orthopaedic hospital and a rehabilitation clinic it will be examined which factors lead to successful implementation of the services and measures designed.METHOD:A qualitative research design was developed comprising different methods of data assessment (participant observation, guided expert interviews, document analyses) enabling a comprehensive exploration. Overall, data were derived from six consultations with patients, two integrated care information sessions and various documents (17 patient files, information material, patient lists, etc.).RESULTS:First of all, the different phases of development and implementation of integrated care settings were described. In this context, clearly defined aims, structures and appropriate measures seem to be crucial for an ideal long-term cooperation. Furthermore, the staff perspective on the effects of the IC programme on their daily routines proved an essential basis for process reconstruction. The staff members pointed out four main aspects regarding IC settings, i. e., improved image, increased knowledge, intensity of relationship, and less and more work effort. Against this background, factors of successful IC settings could be generated such as the need for central coordination, a regular staff information systems as well as accompanying process monitoring.CONCLUSION:Several key factors of successful integrated care settings in arthroplasty could be generated which provide important clues for shaping future interdisciplinary and cross-sectoral cooperation settings in health care services in general.

Objective: In spite of the cumulating evidence for the prognostic relevance of illness perceptions regarding the course of disease and recovery of hip and knee joint patients, there are still no studies that examine the effects of these perceptions on postoperative functioning as assessed by clinical ratings. The aim of this inception cohort study was to describe the course of functioning following a hip or knee joint replacement over a period of one year and to analyse moderator-type effects of illness perceptions in order to develop strategies for preoperative counselling and postoperative rehabilitation.Methods: The course of functioning following a hip joint replacement was assessed by the Harris hip score (HHS), the course of functioning following a knee joint replacement by the American Knee Society score (AKSS). Illness perceptions were assessed by the brief illness perception questionnaire. Due to the non-linear relationship of time and functional outcome, time was transformed using a log transformation. Moderator-type effects were analysed by interaction terms of log time and illness perceptions.Results: For 135 patients the course of the HHS was analysed, for 127 patients the course of the AKSS. Results after one year confirmed a successful treatment for 82.3% of the hip patients and 70.6% of the knee patients. Hip patients expecting an enduring illness had lower scores on the HHS after one year (p = 0.026). The expectation that the treatment will be helpful was associated with a better outcome (p = 0.002). The outcome of knee patients was moderated by the degree how concerned they were about their illness (p = 0.016).Conclusion: The results confirmed the prognostic relevance of illness perceptions for the functional outcome and indicate the importance of preoperative counselling and the potential benefit of patient-oriented education that is aimed at modifying illness perceptions.

Die Arbeit in der Notaufnahme stellt hohe Anforderungen an die fachlichen und individuellen Kompetenzen, an die Belastbarkeit der Mitarbeiter sowie an die Gestaltung der Arbeitsabläufe. Im Rahmen der Notfallintervention zeigt sich darüber hinaus ein hohes Risikopotential für gewaltförmige Interaktionsprozesse.

Background. Working in the accident and emergency department puts high demands on professional and individual competencies, resources and staff coping strategies as well as on the arrangement of workflow. Furthermore, this field of work is associated with a high risk of violent interactions.Aim. This article reviews the current research and shows that the phenomenon of violence in accident and emergency departments is widely documented and discussed internationally, but no precise knowledge about its causes and conditions has been identified up to now.Results. A methodological approach is presented that focuses on the different forms, motives, conditions, and dynamics of interactions influencing violent situations in the emergency accident department. Systematic documentation, typology and analyses using qualitative research methods are discussed.

BackgroundWorking in the accident and emergency department puts high demands on professional and individual competencies, resources and staff coping strategies as well as on the arrangement of workflow. Furthermore, this field of work is associated with a high risk of violent interactions.AimThis article reviews the current research and shows that the phenomenon of violence in the accident and emergency department is widely documented and discussed internationally, but no precise knowledge about its causes and conditions has been identified up to now.ResultsA methodological approach is presented that focuses on the different forms, motives, conditions, and dynamics of interactions influencing violent situations in the accident department. Systematic documentation, typology and analyses using qualitative research methods are discussed.

Objective: The role of cAMP in beta(2)-adrenoceptor signaling and its functional relevance in adult rat heart has been the Subject of considerable controversy. Therefore, we investigated the beta(2)-adrenoceptor pathways in both adult cardiomyocytes and in the intact hearts of Wistar rats with respect to protein kinase A (at Sei-16)-, the key event in shortening of relaxation time, and CaM kinase II (at Thr17)-dependent phospholamban phosphorylation. Methods: Contractile and Cellular beta(1)/beta(2)-adrenergic responses were studied in parallel on the same perfused rat heart. (-)Isoproterenol and the beta(2)-adrenergic agonists zinterol and procaterol were used to discriminate the beta-adrcnoceptor subtype-related actions. Results: beta(2)-Adrenoceptor stimulation induces protein kinase A-dependent phospholamban phosphorylation in both adult cardiomyocytes and in adult hearts of rats. The beta(2)-adrenoceptor-mediated shortening of relaxation time in the heart correlates with Ser16 phosphorylation. Adenosine elicited antiadrenergic action on both beta(1)- and beta(2)-adrenergic signaling cascades by reducing the phosphorylation Status of phospholamban. Only beta(1)-adrenoceptor stimulation produced significant CaM kinase II-related Thr17 phosphorylation. troponin I phosphorylation and activation of phosphorylase. Conclusions: Our findings clearly show that beta(2)-adrenoceptor signaling is coupled to phospholamban phosphorylation and shortening of relaxation time in the adult rat heart. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Calcium-dependent mechanisms and the renin angiotensin system (RAS) are critically involved in the hypertrophic growth of the myocardium. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous mediator in calcium signaling and modulates calcium handling and growth mechanisms in cardiomyocytes. Here we present data on expression of cardiac isoforms of CaMKIIδ, the dominant form in the myocardium, in compensatory hypertrophy of stroke-prone spontaneously hypertensive rats (SHRSP) compared to the normotensive Wistar-Kyoto (WKY) control strain. Cardiac hypertrophy in SHRSP was documented by an increased heart weight/body weight ratio (HW/BW) of 31 % (p < 0.05) and a more than six-fold elevated atrial natriuretic factor (ANF) transcript level (p < 0.05). Compensatory hypertrophic growth in SHRSP produced a specific phenotype of CaMKIIδ isoforms characterized by increased transcript levels of the embryonic/neonatal isoform δ 4 (48 %, p < 0.05) and the isoform δ 9 (31 %, p < 0.05) with no changes in δ 2 and δ 3 . Inhibition of angiotensin converting enzyme (ACE) by cilazapril completely regressed myocardial hypertrophy, normalized ANF transcript levels, and restored the normal phenotype of CaMKIId by reducing transcripts for δ 4 and δ 9 to levels present in WKY controls. Our data suggest the importance of specific changes in the CaMKII isoform composition for growth processes in the myocardium.

In double transgenic rats (dTGR) harboring the human angiotensinogen (hAOGEN) and human renin (hREN) genes, we studied cardiac transcript levels of hypertrophy-related, Ca2+ regulatory, and beta-adrenoceptor-associated proteins. The contractile properties and the cellular signaling of isolated hearts exposed to (-)isoproterenol and/or angiotensin (Ang) I were evaluated. dTGR developed hypertension of 174.1 +/- 7.6 versus 109.6 +/- 2.0 mm Hg (P<0.05) in Sprague-Dawley rats and heart hypertrophy. In hearts of dTGR, the transcript levels of ANP, beta-MHC, and alpha-MHC were altered (percentage versus Sprague-Dawley rats, 100%) by 304%, 178%, and 78%, respectively. Transcript levels of L-type Ca2+ channel, Ca2+ release channel, SERCA2a, phospholamban, G(i) and G(s)-proteins were unchanged. Isolated hearts of dTGR indicated higher baseline contractility versus Sprague-Dawley rats. (-)Isoproterenol-modified contractility occurred in both groups; however, the extent (predrug value, 100%) was less in hearts of dTGR versus Sprague-Dawley rats (+dP/dt, 310 +/- 42% versus 534 +/- 63%; P<0.05). Interestingly, (-) isoproterenol shortened the relaxation time by approximate to25% in both groups. This finding was reflected by a protein kinase A-related phospholamban phosphorylation. Ang I depressed the heart contractility but did not interact with the protein kinase A pathway. In conclusion, we have found that expression of the hAOGEN-hREN complex in dTGR elicited specific effects on transcripts of ANP and myofibrillar proteins. Although the beta-adrenergically mediated relaxation was not impaired in the hypertrophied hearts, the extent of beta-adrenergic inotropic responsiveness was reduced.

Objectives We investigated cardiac function in rats transgenic for the human renin and angiotensinogen genes (TGR) to test the hypothesis that elevated local angiotensin II precipitates adrenergic dysfunction and abnormal contractile function. Methods Hearts from TGR and Sprague–Dawley control rats, aged 6 weeks, were studied using the Langendorff model and papillary muscle preparations (n = 6–10 per group). Incremental isoproterenol (1–1000 nmol/l) and external Ca2+-concentrations (0.75–6.0 mmol/l) were tested. Cardiac protein and mRNA expression levels were determined by Western blot and RNAase protection assay. Results TGR rats showed left ventricular hypertrophy (54%), higher blood pressures (76 mmHg), and elevated plasma renin activity (seven-fold) compared to controls (P< 0.01). The effect of isoproterenol on TGR rat systolic and diastolic left ventricular performance was decreased in both in-vitro models compared to controls (two- to three-fold, P< 0.01) . TGR rat papillary muscles showed impaired force generation with abnormal basal and Ca2+-dependent relaxation. Giα2 and Giα3 protein levels were increased (20–30%) and SERCA2a and adenylyl cyclase protein levels were decreased (23 and 37%, respectively) in TGR hearts compared to controls, while Gsα or β1 and β2-receptor levels were unchanged. Cardiac angiotensin converting enzyme and atrial natriuretic peptide mRNA levels were increased more than four-fold in TGR with no differences for the angiotensin type1 receptor, β1-receptor, SERCA2a, phospholamban, adenylyl cyclase V and angiotensinogen genes. Conclusions TGR rat hearts develop severe adrenergic dysfunction with decreased adenylyl cyclase and abnormal intracellular Ca2+-homeostasis. Our findings emphasize angiotensin II as a major risk factor promoting early functional decline in cardiac hypertrophy. The data may have implications for patients with activating polymorphisms of the renin–angiotensin system and support the need for an early therapeutic intervention.

BACKGROUND In adult human heart, both beta(1)- and beta(2)-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of beta(1)- and beta(2)-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. METHODS AND RESULTS Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 21/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(2)-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC(50) [mol/L] NE 5.5+/-0.1, n=12; EPI 5.6+/-0.1, n=13 patients), hastening of the time to reach peak force (-log EC(50) [mol/L] NE 5.8+/-0.2; EPI 5.8+/-0.2) and 50% relaxation (-log EC(50) [mol/L] NE 5.7+/-0.2; EPI 5.8+/-0.1). Ventricular membranes from Fallot infants, labeled with (-)-[(125)I]-cyanopindolol, revealed a greater percentage of beta(1)- (71%) than beta(2)-adrenergic receptors (29%). Binding of (-)-epinephrine to beta(2)-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to beta(1)-receptors. CONCLUSIONS Despite their low density, beta(2)-adrenergic receptors are nearly as effective as beta(1)-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.

Left ventricular hypertrophy (LVH) entails numerous functional and molecular changes that ultimately lead to cardiac insufficiency. The renin-angiotensin system and adrenergic receptor signalling pathway have both been implicated in LVH progression and interactions between these factors may precipitate contractile dysfunction. We therefore investigated cardiac function in hypertensive rats transgenic for the human renin and angiotensinogen genes (TGR) having a genetic activation of the renin-angiotensin system, stroke-prone spontaneously hypertensive rats (SHR) and normotensive controls (CTR) aged 6 weeks. The isolated perfused heart model was used and the effect of isoproterenol (0.1-1000 nmol/L on cardiac function was studied. Cardiac protein and gene expression was studied by Western blot and RNase protection assay. TGR had 75 mmHg higher blood pressure and a 24% higher cardiac/body weight ratio than CTR; blood pressure in SHR was 17 mmHg higher without heart weight difference (p < 0.05). Basal Pmax, +dP/dt and -dP/dt were higher in TGR and SHR compared with CTR hearts. Isoproterenol stimulated these parameters by a maximum factor 6-8 in CTR and SHR but had almost no effect in TGR (p < 0.05). Basal CF per g heart weight was similar in all experimental groups. Isoproterenol produced a significantly smaller vasodilation in TGR compared with CTR or SHR. beta 1 and beta 2 receptor and Gs alpha proteins were similar in TGR, SHR and CTR. Gi alpha was increased in TGR hearts (p < 0.05). Converting enzyme and atrial natriuretic factor mRNA expression was increased (p < 0.01) while beta 1 receptor, adenylyl-cyclase V, SERCA2a and phospholamban mRNA expression was unchanged in TGR compared with CTR. Thus, LVH in TGR is characterised by early adrenergic dysfunction and beta 1 receptor signalling abnormalities indicating progressive functional deterioration. The data may serve as support for an early preventive intervention in angiotensin-II dependent cardiac hypertrophy and may have also implications for patients with genetic alterations of the renin-angiotensin system.

OBJECTIVES This study was designed to investigate the effects of cardiodepressant substances released from postischemic myocardial tissue on myocardial calcium-regulating pathways.BACKGROUND We have recently reported that new cardiodepressant substances are released from isolated hearts during reperfusion after myocardial ischemia.METHODS After 10 min of global ischemia, isolated rat hearts were reperfused and the coronary effluent was collected for 30 s. We tested, the effects of the postischemic coronary effluent on cell contraction, Ca2+ transients and Ca2+ currents of isolated rat cardiomyocytes by applying fluorescence microscopy the whole-cell, voltage-clamp technique. Changes in intracellular phosphorylation mechanisms were studied by measuring tissue concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), as well as activities of cAMP-dependent protein kinase (cAMP-dPK) and protein kinase C (PKC).RESULTS The postischemic coronary recent, diluted with experimental buffer, caused a concentration dependent reduction of cell shortening and Ca2+ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca2+ current in voltage-clamped cardiomyocytes. The current reduction resulted from reduced maximal conductance-not from changes in voltage- and time-dependent gating of L-type Ca2+ channel. The postischemic coronary effluent modified neither the tissue concentrations of cAMP or cGMP nor the activities of cAMP-dPK and PKC. However, the effluent completely eliminated the activation of glycogen phosphorylase after beta-adrenergic stimulation,CONCLUSIONS Negative inotropic substances released from isolated postischemic hearts reduce Ca2+ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca2+ channels. (C) 2001 by the American College of Cardiology.

The site-specific phospholamban phosphorylation was studied with respect to the interplay of cAMP- and Ca2+signaling in neonatal rat cardiomyocytes. To elucidate the signal pathway(s) for the activation of Ca2+/calmodulin-dependent protein kinase (CaMKII) we studied Thr17 phosphorylation of phospholamban in dependence of Ca2+channel activation by S(-)-Bay K8644 and in dependence of the depletion of the sarcoplasmic reticulum Ca2+stores by ryanodine or thapsigargin in the absence or presence of β -adrenergic stimulation. The isoproterenol (0.1 μM)-induced Thr17 phosphorylation was potentiated 2.5-fold in presence of 1 μM S(-)-Bay K8644. Interestingly, S(-)-Bay K8644 alone was also able to induce Thr17 phosphorylation in a dose- and time-dependent fashion. Ryanodine (1.0 μM) reduced both the isoproterenol (0.1μM ) and S(-)-Bay K8644-(1 μM) mediated Thr17 phosphorylation by about 90%. Thapsigargin (1 μM) diminished the S(-)-Bay K8644 and isoproterenol-associated Thr17 phosphorylation by 53.5±6.3% and 92.5±11.1%, respectively. Ser16 phosphorylation was not affected under these conditions. KN-93 reduced the Thr17 phosphorylation by S(-)-Bay K8644 and isoproterenol to levels of 1.1±0.3% and 8.6±2.1%, respectively. However, the effect of KN-93 was attenuated (47.8±3.6%) in isoproterenol prestimulated cells. Protein phosphatase inhibition by okadaic acid increased exclusively the Ser16 phosphorylation. In summary, our results reflect a cross-talk between β -adrenoceptor stimulation and intracellular Ca2+at the level of CaMKII-mediated phospholamban phosphorylation in neonatal rat cardiomyocytes. We report conditions which exclusively produce Thr17 or Ser16 phosphorylation. We postulate that Ca2+transport systems of the sarcoplasmic reticulum are critical determinants for the activation of CaMKII that catalyzes phosphorylation of phospholamban.

Phospholamban is a critical regulator of sarcoplasmic reticulum Ca 2+ -ATPase and myocardial contractility. To determine the extent of cross signaling between Ca 2+ and cAMP pathways, we have investigated the β-adrenergic-induced phosphorylation of Ser 16 and Thr 17 of phospholamban in perfused rat hearts using antibodies recognizing phospholamban phosphorylated at either position. Isoproterenol caused the dose-dependent phosphorylation of Ser 16 and Thr 17 with strikingly different half-maximal values (EC 50 = 4.5 ± 1.6 and 28.2 ± 1.4 nmol/l, respectively). The phosphorylation of Ser 16 induced by isoproterenol, forskolin, or 3-isobutyl-1-methylxanthine correlated to increased cardiac relaxation ( r = 0.96), whereas phosphorylation of Thr 17 did not. Elevation of extracellular Ca 2+ did not induce phosphorylation at Thr 17 ; only in the presence of a submaximal dose of isoproterenol, phosphorylation at Thr 17 increased eightfold without additional effects on relaxation rate. Thr 17 phosphorylation was partially affected by ryanodine and was completely abolished in the presence of 1 μmol/l verapamil or nifedipine. The data indicate that 1) phosphorylation of phospholamban at Ser 16 by cAMP-dependent protein kinase is the main regulator of β-adrenergic-induced cardiac relaxation definitely preceding Thr 17 phosphorylation and 2) the β-adrenergic-mediated phosphorylation of Thr 17 by Ca 2+ -calmodulin-dependent protein kinase required influx of Ca 2+ through the L-type Ca 2+ channel.

Forskolin and dibutyryl cyclic adenosine monophosphate (cAMP) stimulate force of contraction independent of beta-adrenoceptor stimulation. We studied their effects on force of contraction and phosphorylation of regulatory proteins in isolated electrically driven trabeculae carneae from failing human ventricles. The phosphorylation state of the regulatory protein phospholamban was studied because its phosphorylation usually faithfully follows contractility. For comparison, the phosphorylation state of the inhibitory subunit of troponin was studied. The phosphorylation state was inferred from in vitro phosphorylation of homogenates with cAMP-dependent protein kinase in the presence of radioactive gamma[P-32]ATP. Proteins were separated by electrophoresis, and radioactivity in the proteins of interest was quantified. The maximal positive inotropic effects occurred at 30 mu M forskolin and were attenuated in comparison with the maximal effects to dibutyryl cAMP (1 mM). Both forskolin and dibutyryl cAMP enhanced phospholamban phosphorylation. However, phospholamban phosphorylation in intact trabeculae treated with 30 mu M forskolin and 1 mM dibutyryl cAMP was comparable. It is suggested that phospholamban phosphorylation can be dissociated from inotropy at least in isolated trabeculae from failing human hearts.

The intracellular mechanisms underlying the action of the endogenous vasodilators such as NO/EDRF, adenosine, and prostacyclin acting through cGMP and cAMP, respectively, are not well understood. One important action of cyclic nucleotides in smooth muscle relaxation is to lower the cytosolic Ca2+ concentration by enhanced sequestration into the sarcoplasmic reticulum. The present study was undertaken to elucidate the potential role of phosphorylation of phospholamban, the regulator of sarcoplasmic reticulum Ca2+ pump, for the control of coronary vascular tone by NO/EDRF, adenosine, and prostacyclin. Phospholamban was identified in pig coronary artery preparations by immunofluorescence microscopy, Western blotting and in vitro phosphorylation. Segments of pig coronary artery, with either intact or denuded endothelium, were precontracted with prostaglandin F-2 alpha (PGF(2 alpha)). in endothelium-denuded preparations 3-morpholinosydnonimine (SIN-1), 5'-N-ethylcarboxiamidoadenosine (NECA), and iloprost (ILO) caused both relaxation and phospholamban phosphorylation with the potency: SIN-1 > NECA > ILO. The regulatory myosin light chain was significantly dephosphorylated only by SIN-1. In endothelium-intact pig coronary artery L-NAME caused additional vasoconstriction and a decrease in phospholamban phosphorylation, while phosphorylation of myosin light chain remained unchanged. An inverse relationship between phospholamban phosphorylation and vessel tone was obtained. Our findings demonstrate significant phospholamban phosphorylation during coronary artery relaxation evoked by NO, prostacyclin, and adenosine receptor activation. Because of the close correlation between phosphorylation of phospholamban and vessel relaxation, we propose that phospholamban phosphorylation is an important mechanism by which endogenous vasodilators, especially endothelial NO/EDRF, control coronary vascular smooth muscle tone. (C) 1998 Wiley-Liss, Inc.