Discrimination between healthy and degenerated bovine articular cartilage with a fiber Bragg grating based microindenter.

OBJECTIVE: In this study we aim to show that an optical fiber Bragg grating-based microindentation system, which has the potential to be deployed arthroscopically, can differentiate between healthy and degenerated articular cartilage, which represents an important challenge in minimally-invasive surgery. DESIGN: Twenty bovine osteochondral cylinders, extracted from the patellar groove of ten 24 months old animals were subjected to stepwise in vitro stress-relaxation indentation measurements. The indentation procedure comprised 15 indentation steps of 20 µm each, reaching a total depth of 300 µm. Ten samples remained untreated and served as a control group for healthy cartilage. A second group of ten samples was treated for 12 h with an aqueous trypsin solution (concentration 2.5%) to deplete the proteoglycans. For both groups and all indentation depths deeper than 100 µm, the step response functions of a two elements Maxwell-Wiechert model fitted well to the measured relaxation curves. RESULTS: The standard deviations of the identified stiffness parameters within each group were much smaller than the difference of the average stiffness values between both groups. Based on the measured stiffness values, the system was capable to discriminate between healthy and degenerated cartilage with a high level of significance (p < 0.001). The experimental results are also discussed in terms of the biomechanical changes of cartilage under the action of trypsin. CONCLUSION: The fiber Bragg grating microindentation system showed the capability to differentiate intact and proteoglycan depleted cartilage with high significance.

Multiscale modeling reveals inhibitory and stimulatory effects of caffeine on acetaminophen-induced toxicity in humans.

Acetaminophen (APAP) is a widely used analgesic drug that is frequently co-administered with caffeine (CAF) in the treatment of pain. It is well known that APAP may cause severe liver injury after an acute overdose. However, the understanding of whether and to what extent CAF inhibits or stimulates APAP-induced hepatotoxicity in humans is still lacking. Here, a multiscale analysis is presented that quantitatively models the pharmacodynamic (PD) response of APAP during co-medication with CAF. Therefore, drug-drug interaction (DDI) processes were integrated into physiologically based pharmacokinetic (PBPK) models at the organism level, whereas drug-specific PD response data were contextualized at the cellular level. The results provide new insights into the inhibitory and stimulatory effects of CAF on APAP-induced hepatotoxicity for crucially affected key cellular processes and individual genes at the patient level. This study might facilitate the risk assessment of drug combination therapies in humans and thus may improve patient safety in clinical practice.

Patients' satisfaction with community treatment: a pilot cross-sectional survey adopting multiple perspectives.

ACCESSIBLE SUMMARY: Patients' satisfaction is scarcely studied within the context of community treatment for adolescents. Thus, this study adopts a multiple perspective on patients' satisfaction (including service users as well as staff members). The results highlighted that all informants (patients, foster carers in foster homes and professional caregivers from community treatment teams) perceived the patients to be satisfied, with foster carers reporting the highest patient satisfaction rate. Considering the patient satisfaction rate from multiple perspectives provides complementary understandings. Clinical outcomes and, specifically, a reduction in emotional difficulties were related to patient's satisfaction, but only from the patients' perspective. ABSTRACT: Community treatment (CT) teams in Switzerland provide care to patients who are unable to use regular child and adolescent mental health services (i.e. inpatient and outpatients facilities). No study has considered patients' self-rated satisfaction alongside with staff members' perspectives on patient satisfaction. Thus, adopting a cross-sectional survey design, we collected patients' satisfaction using the Client Satisfaction Questionnaire (CSQ-8), rated by multiple informants (patients, foster carers in foster homes and professional caregivers from CT teams). Professional caregivers assessed clinical outcomes using the Health of the Nation Outcome Scale for Children and Adolescents. The results indicated that all informants were satisfied with the community treatment teams. The satisfaction scores were not correlated across informants; however, the alleviation of emotional symptoms was correlated with patients' satisfaction. This study indicated that the use of a combined approach including the views of service users and professionals gives important complementary information. Finally, in our sample, lower emotional symptoms were linked to enhanced patient satisfaction. This study demonstrated the importance of considering multiple perspectives to obtain the most accurate picture of patients' satisfaction. Second, focusing on the reduction of emotional symptoms might lead to a higher degree of patients' satisfaction.

[Extension of mobile team services to the home: pilot project in the Vaud canton]. / Extension des prestations de type "équipe mobile" aux foyers socio-éducatifs: projet pilote dans le canton de Vaud.

The main objective of this project about mobile team service extension to the socio-educational home of the whole Vaud canton targets to decompartmentalize the socio-educational and youth-psychiatry domains. 64 patient were assessed during this pilot phase (after one-year functioning). In addition, a satisfaction survey was done either at the end of the follow up or at the end of the pilot phase of the project (31.12.2012). This experience was very positive as highlighted by the vast majority of the person involved in the socio-educational and youth-psychiatric domains taking care of youth. A desire of extension of mobile team service to other institutional structure or other situations was expressed.

[Psychiatric mobile teams for the three ages of live: the Lausanne experience]. / Equipes de psychiatrie mobiles pour les trois âges de la vie: l'expérience lausannoise.

Mobile teams have been developed for the three ages to meet the needs of people who should receive--but do not access to--a psychiatric assessment or to specialized care. To achieve this goal, the teams built a strong partnership within the social network, both with relatives and professionals involved. The general principles of intervention are similar between the ages: a focused target population, assertive outreach which benefits also relatives and carers, multidisciplinary teams with a limited caseload to ensure availability. The specificities of each age will be analyzed.

Linear and nonlinear methods for analyses of cardiovascular variability in bipolar disorders.

OBJECTIVES: Heart rate variability (HRV), blood pressure variability (BPV), and the assessment of baroreflex sensitivity are widely accepted methods for analyzing and characterizing cardiovascular regulation and for an enhanced risk evaluation in different diseases. As a result of the complexity of the investigated regulatory systems, univariate analyses do not often provide a convenient description of pathological changes in the cardiovascular regulation. Therefore, the application of a multivariate approach is preferable. METHODS: We present principal methods of time-domain, frequency-domain, and nonlinear analyses of HRV, BPV as well as methods for coupling and interaction analyses. RESULTS: Changes in autonomic nervous system (ANS) tone are known to accompany various mental disorders. Depressive patients frequently complain of symptoms of ANS dysfunction, such as dry mouth, diarrhea, and insomnia. These clinical observations propose the assumption of altered autonomic dysfunction in these patients. In contrast to these clinical assumptions, inconsistent results have been found in studies of HRV in depressive patients. This work therefore covers a brief review of the literature in respect to bipolar disorder and the rationale to study autonomic changes in such a psychiatric disease. CONCLUSIONS: Prospective studies of cardiovascular changes in mania and depression are needed to evaluate a psychopathological state in connection with cardiovascular changes and cardiac morbidity and mortality. These studies should consider BPV, coupling and interaction analyses, the application of nonlinear methods, and a multivariate approach in addition to the traditional analysis of HRV.

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders.

Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.

Diagnosing aortic valve stenosis by correlation analysis of wavelet filtered heart sounds.

Traditional auscultation performed by the general practitioner remains problematic and often gives significant results only in a late stage of heart valve disease. Valve stenoses and insufficiencies are nowadays diagnosed with accurate but expensive ultrasonic devices. This study aimed to develop a new heart sound analysis method for diagnosing aortic valve stenoses (AVS) based on a wavelet and correlation technique approach. Heart sounds recorded from 373 patients (107 AVS patients, 61 healthy controls (REF) and 205 patients with other valve diseases (OVD)) with an electronic stethoscope were wavelet filtered, and envelopes were calculated. Three correlations on the basis of these envelopes were performed: within the AVS group, between the groups AVS and REF and between the groups AVS and OVD, resulting in the mean correlation coefficients rAVS, rAVSv.REF and rAVSv.OVD. These results showed that rAVS (0.783 +/- 0.097) is significantly higher (p < 0.0001) than rAVSv.REF (0.590 +/- 0.056) and rAVSv.OVD (0.516 +/- 0.056), leading to a highly significant discrimination between the groups. The wavelet and correlation-based heart sound analysis system should be useful to general practitioners for low-cost, easy-to-use automatic diagnosis of aortic valve stenoses.

Forecasting of life threatening arrhythmias using the compression entropy of heart rate.

OBJECTIVES: Ventricular tachycardia (VT) provoking sudden cardiac death (SCD) are a major cause of mortality in the developed countries. The most efficient therapy for SCD prevention are implantable cardioverter defibrillators (ICD). In this study heart rate variability (HRV) measures were analyzed for short-term forecasting of VT in order to improve VT sensing and to enable a patient warning of forth-coming shocks. METHODS: The last 1000 normal beat-to-beat intervals before 50 VT episodes stored by the ICD were analyzed and compared to individually acquired control time series (CON). HRV analysis was performed with standard parameters of time and frequency domain as suggested by the HRV Task Force and furthermore with a newly developed and optimized nonlinear parameter that assesses the compression entropy of heart rate (Hc). RESULTS: Except of meanNN (p = 0.02) we found no significant differences in standard HRV parameters. In contrast, Hc revealed highly significant (p = 0.007) alterations in VT compared with CON suggesting a decreased complexity before the onset of VT. CONCLUSION: Compression entropy might be a suitable parameter for short-term forecasting of life-threatening tachycardia in ICD.

[Heart rate and blood pressure interaction in normotensive and chronic hypertensive pregnancy]. / Herzfrequenz- und Blutdruckinteraktion bei normotensiver und chronisch hypertensiver Schwangerschaft.

Pregnancy has impact on autonomic control. Since hypertensive pregnancy disorders are a major cause of maternal mortality we investigated the baroreflex sensitivity (BRS) in chronic hypertensive pregnant women (CH), normotensive pregnant (PRE) and non-pregnant (NPRE) women. In addition to the traditional 'sequence method' we used joint symbolic dynamics (JSD). BRS was significantly reduced in all pregnancies compared with NPRE (p < 0.00001) but there was no significant difference between CH and PRE. Contrary, the JSD measures revealed significant differences (p < 0.00001) in the heart rate and blood pressure interactions between PRE and CH. In conclusion, JSD measures uncovered a different gestation related adaptation of autonomic regulation in women with chronic.

[Effect of post-extrasystole potentiation on blood pressure and heart rate regulation]. / Einfluss der postextrasystolischen Potenzierung auf Blutdruck und Herzfrequenzregulation.

Noninvasive finger arterial blood pressure and ECG were recorded for 30 min in patients with idiopathic dilated cardiomyopathy (IDC) and healthy control subjects (CON) for the investigation of blood pressure and heart rate regulation following a premature ventricular complex (PVC). The potentiation of blood pressure amplitude of the postextrasystolic beat was fivefold increased in IDC compared with CON (48.7 +/- 32.6% vs. 9.8 +/- 5.4%, p < 0.01). PVC starts a baroreflex response, which last about 10 s in physiological regulation. In contrast, the baroreflex response in IDC is immediately suppressed by the augmented potentiation of the blood pressure amplitude from the first postextrasystolic beat. Thus, the regulation after PVC is determined by the PVC itself and postextrasystic potentiation.

[Afterload and blood pressure amplitude in dilated cardiomyopathy]. / Nachlast und Blutdruckamplitude bei dilatativer Kardiomyopathie.

The beat-to-beat variability of the diastolic blood pressure induces small variations in the afterload of the left ventricle. These variations influence myocardial contractility, and thus blood pressure amplitude. We assessed the interdependence of blood pressure and changes in the afterload. We continuously recorded blood pressure (duration 200 s, at rest) in 20 patients with dilated cardiomyopathy (ejection fraction 32 +/- 13%, left ventricular diameter 67 +/- 8 mm) and in 20 healthy volunteers. Interbeat intervals, diastolic pressures, systolic pressure amplitudes and mean slopes of systolic pressure amplitudes were measured. Correlation coefficients (r) were calculated to assess the interdependence of blood pressure amplitudes/mean systolic slopes and the preceding diastolic pressures/interbeat intervals, respectively. In healthy volunteers we found a strong interdependence between blood pressure amplitude and the preceding diastolic pressures (r = 0.62 +/- 0.21 and 0.47 +/- 0.22). Higher diastolic pressures were followed by higher blood pressure amplitudes, and by steeper slopes of the systolic peaks. In patients with dilated cardiomyopathy, such interdependence was significantly lower (r = 0.33 +/- 22 and r = 0.28 +/- 0.35), and in patients with severely reduced left ventricular function (ejection fraction < 32%) was only marginal (r = 0.23 +/- 0.27 and 0.21 +/- 0.44, respectively). The forces of the isovolumetric contraction necessary to initiate the ejection phase of the left ventricle depend on the afterload, i.e. on the diastolic pressure. The responses of amplitude and slope of the systolic blood pressure to small changes in the afterload make it possible to assess left ventricular contractility. The latter is impaired in dilated cardiomyopathy.

High frequency intra-QRS signals in idiopathic dilated cardiomyopathy.

We extracted and quantified high frequency intra-QRS signals in idiopathic dilated cardiomyopathy (IDC). In IDC the analysis of late potentials in the terminal QRS complex often fails in predicting clinical events because of intraventricular conduction abnormalities and the absence of a circumscribed arrhythmogenic substrate. Therefore, new approaches are required to assess the electrical state of the myocardium. We investigated 21 patients suffering from IDC with (n = 14) and without (n = 7) bundle branch block. High resolution 31 lead magnetocardiograms were filtered with a 67 point 4th order Savitzky-Golay filter. The difference of the measured and filtered signals was calculated (67-200 Hz). The spatio-temporal properties and the areas under the curves of the resulting high frequency intra-QRS signals (IQCs) were studied. We detected IQCs in all patients. The patients had individual patterns regarding the temporal and spatial properties of the IQCs during depolarisation. The IQCs predominantly appeared in the initial portion of the QRS. The ratios of the areas under the curves of the IQCs and the measured signals were linearly correlated to the left ventricular enddiastolic diameter (r = 0.71, significance 0.0012). In IDC the ventricular depolarization is accompanied by individual spatial and temporal patterns of high frequency intra-QRS signals. They can be studied non-invasively from body surface mapping data with the algorithm used in this study. This provides access to the assessment of the electrical status in patients with IDC.

Methods for the computational localization of atrio-ventricular pre-excitation syndromes.

BACKGROUND: The site of atrioventricular pre-excitation can roughly be estimated with the help of schemes basing on a few number of electrocardiogram (ECG) leads. Computer algorithms have been developed which utilize the body surface mapping of the pre-excitation signal for the localization purpose. We tested several new algorithms. METHOD: A patient suffering from Wolff-Parkinson-White syndrome was investigated prior the catheter ablation. The body surface mapping was performed with a 62-lead magnetocardiograph. The site of pre-excitation was calculated by using different methods: the dipole method with fixed and moving dipoles, the dipole scan on the endocardium, and different current density methods (L1 norm method, L2 norm method, low resolution electromagnetic tomography (LORETA) method, and maximum entropy method). Three-dimensional (3D) magnetic resonance imagings (MRIs) of the heart were used to visualize the results. The source positions were compared to the site of catheter ablation. RESULTS: The accessory pathway was successfully ablated left laterally. This site was correctly identified by the conventional dipole method. By scanning the entire endocardial surface of the heart with the dipole method we found a circumscribed source area. This area too, was located at the lateral segment of the atrio-ventricular grove. The current density methods performed differently. Whereas the L1 norm identified the site of pre-excitation, the L2 norm, the LORETA method and the maximum entropy method resulted in extended source areas and therefore were not suited for the localization purpose. CONCLUSION: The dipole scan and the L1 norm current density method seem to be useful additions in the computational localization of pre-excitation syndromes. In our single case study they confirmed the localization results obtained with the dipole method, and they estimated the size of the suspected source region.

Temporal properties of high frequency intra-QRS signals in myocardial infarction and healthy hearts.

The prevalence of late potentials after myocardial infarction depends on the site of the infarction. This may be caused by the different activation onsets of the anterior and inferior myocardial segments. Therefore, in anterior infarcts the high frequency signals may be concealed within the QRS whereas in the inferior infarcts they last beyond the end of the QRS. We compared the timing and the spatial patterns of high frequency intra-QRS signals (IQSs) in the different infarction sites. We investigated 14 patients with anterior infarcts, 17 patients with inferior infarcts, and 10 healthy subjects. 31-lead magnetocardiograms were recorded in left precordial position and averaged. The QRS signals were smoothed with a Savitzky-Golay filter. The smoothed QRS signals were subtracted from the measured ones. The difference of the signals (frequency band of about 60-200 Hz) representing the high frequency components was quantified. The percentage of the high frequency signals was calculated for the entire QRS, for the first and for the second half, respectively. We found that in patients with anterior infarcts the high frequency components predominantly appeared in the first half of the QRS whereas in inferior infarcts these components predominantly appeared in the second half of the QRS. The different infarction sites were associated with different spatial patterns of the high frequency signals on the body surface. In healthy subjects there was not such a preferential association of time intervals and high frequency signals. Late potentials are the special case of high frequency signals appearing in the terminal QRS. It is the general property of the myocardium to generate high frequency signals associated with the depolarization of infarcted tissue. The timing of such signals and the spatial distribution patterns on the body surface may help to identify the location of the sources.

[Cardiorespiratory desynchronization after acute myocardial infarct]. / Kardiorespiratorische Desynchronisation nach akutem Myokardinfarkt.

The prognosis of cardiac diseases can be estimated from the variability of regulation parameters of the cardiovascular system. Changes in the variability of a regulation parameter causes disturbances in the synchronisation of interacting control loops. Conclusions about the severity of the underlying functional impairment can be drawn from these disturbances. This study investigates the synchronisation of the control loops of the heart rate and respiration (cardiorespiratory synchronisation, CRS) after acute myocardial infarction. We investigated 43 patients after myocardial infarction and 27 healthy controls. To quantify the CRS the synchronisation in phase of respiration and heart rate was assessed. The heart rate variability (HRV) was also assessed. Patients after myocardial infarction have a significantly reduced HRV and CRS. There is a non-linear relationship between HRV and CRS. Patients with left ventricular enlargement and reduced left ventricular ejection fraction (< or = 45%) significantly differed from the other infarct patients and controls in CRS but not in HRV. They had a marked degree of cardiorespiratory desynchronisation and were identified by a threshold value. CRS is a measure of the interaction of respiration control and heart rate control. After myocardial infarction, a reduction of the HRV can be observed. The desynchronisation of the control loops of respiration and heart rate especially appears in large infarcts. This can be quantitatively assessed by the method presented.

[Effect of choice of baseline correction interval on localization of electrical heart activity]. / Einfluss der Wahl des Basislinien-Korrekturintervalls auf die Lokalisation der elektrischen Herzaktivität.

The electric heart activity can be localised from body surface mapping data with computer algorithms. At higher heart rates the T and P waves merge. Thus, the offset can not be subtracted in the TP segment. We investigated 28 healthy volunteers with signal averaged 31-lead magnetocardiography. The offset of the baseline was determined in the TP-segment and in the PR-segment, respectively. The electrical heart activity was localised in the initial 30 ms of the QRS complex (Q), at the QRS maximum (R), and at the T wave maximum (T). The volume currents were considered by using a boundary element model with the compartments lungs and torso. The 3D positions of the dipoles, the dipole orientations, and the dipole strengths were calculated using the data preprocessed with two different offset correction intervals. The offsets of the TP and PR segments significantly differed one from another. The average deviations of the dipole localisation were within a few centimetres (Q: 20 +/- 31 mm, R: 6 +/- 13 mm, T: 14 +/- 30 mm). However, in a small number of subjects (Q: n = 5, R: n = 2, T: n = 5) we observed a deviation of more than 30 mm. These deviations were not linearly correlated to the differences in the baseline offsets. High resolution recordings continuously detect heart activity in the PR segment. The correction of the baseline in the PR segment instead of the TP segment may introduce artefacts in the source localisation and therefore should be avoided.