Ultrasonic sensor concept to fit a ventricular assist device cannula evaluated using geometrically accurate heart phantoms

Future left ventricular assist devices (LVADs) are expected to respond to the physiologic need of patients; however, they still lack reliable pressure or volume sensors for feedback control. In the clinic, echocardiography systems are routinely used to measure left ventricular (LV) volume. Until now, echocardiography in this form was never integrated in LVADs due to its computational complexity. The aim of this study was to demonstrate the applicability of a simplified ultrasonic sensor to fit an LVAD cannula and to show the achievable accuracy in vitro. Our approach requires only two ultrasonic transducers because we estimated the LV volume with the LV end‐diastolic diameter commonly used in clinical assessments. In order to optimize the accuracy, we assessed the optimal design parameters considering over 50 orientations of the two ultrasonic transducers. A test bench was equipped with five talcum‐infused silicone heart phantoms, in which the intra‐ventricular surface replicated papillary muscles and trabeculae carnae. The end‐diastolic LV filling volumes of the five heart phantoms ranged from 180 to 480 mL. This reference volume was altered by ±40 mL with a syringe pump. Based on the calibrated measurements acquired by the two ultrasonic transducers, the LV volume was estimated well. However, the accuracies obtained are strongly dependent on the choice of the design parameters. Orientations toward the septum perform better, as they interfere less with the papillary muscles. The optimized design is valid for all hearts. Considering this, the Bland‐Altman analysis reports the LV volume accuracy as a bias of ±10% and limits of agreement of 0%–40% in all but the smallest heart. The simplicity of traditional echocardiography systems was reduced by two orders of magnitude in technical complexity, while achieving a comparable accuracy to 2D echocardiography requiring a calibration of absolute volume only. Hence, our approach exploits the established benefits of echocardiography and makes them applicable as an LV volume sensor for LVADs.     

Ca’ Granda,an avant-garde hospital between the Renaissance and Modern age: a unique scenario in European history

The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke of Milan, and was considered for almost five centuries a model for Milanese, Italian and even European healthcare. Attracting patients from all over Europe, the Ca’ Granda distinguished itself for the introduction of new treatments and innovative health reforms. In the burial ground of the hospital still lie the bodies of the deceased patients, who came from the poorest strata of the population. The study of their remains aims to give back a general identity and a story to each of these persons as well as reconstruct a fraction of the sixteenth century population of Milano as concerns lifestyle and disease and examine practises and therapy of this exceptional hospital. It is estimated that about two million commingled bones and articulated skeletons rest in the crypt, together with other types of findings (e.g., ceramic, coins, clothing). These remains are the object of a large project involving various disciplines ranging from humanities to hard sciences. The aim of this paper is to bring this historical gem to the attention of scholars and provide a glimpse of what its contents have already revealed.     

The abstinence syndrome in diazepam-dependent cats is precipitated by Ro 15-1788 and Ro 15-4513 but not by the benzodiazepine receptor antagonist ZK 93426

Diazepam-dependent cats were challenged with different benzodiazepine recognition site ligands 24 h after the last dose of chronic treatment with diazepam (7 mg/kg, i.p. at 08.00 and 20.00 h, for 21 consecutive days). The benzodiazepine derivatives Ro 15-4513 (a partial inverse agonist) and Ro 15-1788 (a pure antagonist), precipitated an abstinence syndrome within minutes after i.p. administration. Abstinence signs included tremors, increased muscle tone, irritability, fear, pupillary dilation and vocalizations. On the contrary, the beta-carboline derivatives ZK 93426 (an antagonist) and FG 7142 (a partial inverse agonist) failed to precipitate abstinence signs in diazepam-dependent cats when given at doses that prevented the acute effects of diazepam. Our results demonstrate that the ability to induce withdrawal signs in diazepam-dependent cats strongly depends on the benzodiazepine structure of the challenge drug since beta-carboline antagonist and partial inverse agonists lack this property.     

In vivo and in vitro validation of reference tissue models for the mGluR5 ligand [11C]ABP688

The primary objective of this study was to verify the suitability of reference tissue-based quantification methods of the metabotropic glutamate receptor type 5 (mGluR₅) with [¹¹C]ABP688. This study presents in vivo (Positron Emission Tomography (PET)) and in vitro (autoradiography) measurements of mGluR₅ densities in the same rats and evaluates both noninvasive and blood-dependent pharmacokinetic models for the quantification of [¹¹C]ABP688 binding. Eleven rats underwent [¹¹C]ABP688 PET scans. In five animals, baseline scans were compared with blockade experiments with the antagonist 1,2-methyl-6-(phenylethynyl)-pyridine (MPEP), and arterial blood samples were drawn and corrected for metabolites. Afterward, saturation-binding autoradiography was performed. Blocking with MPEP resulted in an average decrease of the total distribution volume (V_T) between 43% and 58% (thalamus and caudate-putamen, respectively) but had no significant effect on cerebellar V_T (mean reduction: −0.01%). Comparing binding potential (BP_ND) based on the V_T with noninvasively determined BP_ND revealed an average negative bias of 0.7% in the caudate-putamen and an average positive bias of 3.1% in the low-binding regions. Scan duration of 50 minutes is required. The cerebellum is a suitable reference region for the quantification of mGluR₅ availability as measured with [¹¹C]ABP688 PET in rats. Blood-based and reference region-based PET quantification shows a significant linear relationship to autoradiographic determinations.     

Correlations between the step activity monitor and the DynaPort ADL-monitor

OBJECTIVE: This study was performed to evaluate correlations between the DynaPort activity of daily living monitor and the step activity monitor. DESIGN: Experimental study with repeated measures. BACKGROUND: Physical activity becomes more important to assess quality of life, e.g. after clinical interventions such as joint replacement surgery. METHODS: Nine subjects wore both devices simultaneously for two days. Limitations and technical problems caused by the devices were assessed by a questionnaire. Correlation coefficients were calculated between parameters derived from both instruments. RESULTS: Only small limitations and problems were reported. Significant correlations were found between the number of steps (step activity monitor) and the percentage of locomotion (DynaPort) (r=0.95), between the number of steps and the physical activity index (DynaPort) (r=0.71) and between the physical activity index and the percentage of locomotion (r=0.76). Wilcoxon-tests between the first and second measurement of each subject did not reveal significant differences but correlation coefficients were poor (r=0.16-0.36). CONCLUSIONS: After one day of simultaneously wearing both devices, the percentage of locomotion can be obtained using only the step activity monitor for additional days. Poor correlations between the first and the second measurements of each subject underline the necessity to record further days to acquire the level of human physical activity.     

Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease: results of ten years of prospective surveillance

OBJECTIVE: To assess the early signs, risk factors, and rate of transition from primary Raynaud's phenomenon (primary RP) to secondary RP. METHODS: A clinical sample of 307 consecutive patients with RP was included in a prospective followup study. After an initial screening, 244 patients were classified as having primary RP, of whom 236 were followed up for a mean +/- SD of 11.2 +/- 3.9 years. Patients classified according to the screening as having suspected secondary RP underwent an extended screening program annually until transition to secondary RP occurred. RESULTS: The initial prevalence of secondary RP was 11%. The annual incidence of transition to suspected secondary RP was 2%, and the annual incidence of transition to secondary RP was 1%. Overall, 46 patients were classified as having suspected secondary RP, and 23 of these later were classified as having secondary RP. Older age at onset of RP (hazard ratio 2.59, 95% confidence interval [95% CI] 1.40-4.80), shorter duration of RP at enrollment (hazard ratio 0.87, 95% CI 0.81-0.94), and abnormal findings on thoracic outlet test (hazard ratio 2.69, 95% CI 1.12-6.48) were associated with an increased risk for transition to secondary RP. Compared with patients with suspected secondary RP, those diagnosed as having secondary RP had a higher number and earlier occurrence of pathologic findings. Furthermore, antinuclear antibodies at a titer of > or = 1:320 and positive findings in specific serologic subsets were associated with a significantly increased risk for developing a connective tissue disease. CONCLUSION: Patients diagnosed initially as having primary RP may actually comprise 1 of 3 groups: those with idiopathic RP, those with a rather benign disease course, and those with a more severe course of the disease.