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Biomedical subjects

M Beer

Publications and source records attributed to M Beer.

At least 19 recordsLinked to original sources

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age-matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two-dimensional cine fast low-angle shot sequence was used for the evaluation of absolute values and indices related to 1 m(2) body surface area for function, mass, and LV wall thickening. Fourteen age-matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end-systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year.

Aged↗

[Evaluating signal intensity of movement-impaired myocardial segments in MR delayed images after administration of Gd-DTPA. Correlation of regional increase in contraction after revascularization].

PURPOSE: The aim of the study was to correlate delayed contrast enhancement of dysfunctional regions of the myocardium after injection of Gd-DTPA with the improvement of regional contractility 3 months after revascularization. MATERIAL AND METHODS: Eleven patients with coronary artery disease and wall motion abnormalities underwent MR imaging before and 3 months after revascularization therapy (PTCA or CABG). Short-axis images were acquired using a cine gradient echo sequence. After revascularization, a representative slice was analyzed 14 +/- 1 min after injection of 0.1 mmol/kg Gd-DTPA using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as criterion of viability and was correlated with delayed contrast enhancement patterns. RESULTS: After revascularization, 6 patients showed complete recovery of the dysfunctional area, 1 patient partial recovery, and 4 patients remained unchanged. All 4 patients with persisting wall motion abnormalities, 1/6 patients with recovery and the patient with partial recovery revealed a delayed enhancement. CONCLUSIONS: Three months after revascularization, delayed enhancement of dysfunctional myocardium is evident in patients without regional wall motion improvement, while the lack of delayed enhancement correlates with improvement of regional contractility.

Adult↗

[Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy].

PURPOSE: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. PATIENTS AND METHODS: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. RESULTS: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p = 0.0002) reduced to 0.80 +/- 0.25 in patients compared to 1.65 +/- 0.21 in volunteers. 3 months after SVR, LV mass had significantly (p = 0.04) decreased from 238 +/- 33 g to 206 +/- 47 g. At the same time a significant (p = 0.04) increase of the PCr-ATP ratio from 0.80 +/- 0.25 to 1.28 +/- 0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. CONCLUSIONS: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

Adult↗

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.

We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 +/- 7), women aged under 45 (27 +/- 6), men aged over 45 (59 +/- 8), and women aged over 45 (57 +/- 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 +/- 18 and 110 +/- 16 g; LV EDV, 118 +/- 27 and 96 +/- 21 ml; LV ESV, 40 +/- 13 and 29 +/- 9 ml; RV mass, 52 +/- 10 and 39 +/- 5 g; RV EDV, 131 +/- 28 and 100 +/- 23 ml; RV ESV, 53 +/- 17 and 33 +/- 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4% and 5.9% for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values.

Adult↗

A simple method to check the dynamic performance of electrical impedance tomography systems.

The test concept as well as the design of a simple resistor phantom suitable for the evaluation of the properties of electrical impedance tomographic (EIT) systems is presented. Input and transfer impedance of the phantom are matched with those of the human thorax. Amplitude of the local impedance variations similar to in vivo conditions (ventilation) can be intentionally set to perform measurements on different states. The theoretical potential differences between the electrodes are calculated. The evaluation procedure is performed in terms of the local amplitude of the relative impedance change as well as the local distribution of noise. The whole procedure can be applied either to compare quantitatively the performance of different EIT data acquisition systems or to determine the amount of measurement disturbance caused by the external electrical environment in clinical settings.

Cardiography, Impedance↗

An occupational therapy Internet school.

Four centres in the UK, Belgium, the Netherlands and Sweden have collaborated to provide Internet-based courses for student and professional occupational therapists. The basis of the occupational Therapy Internet School (OTIS) is the concept of the 'virtual college'. This comprises the design and implementation of a sophisticated Internet-based system through which courses can be managed, prepared and delivered on line, and through which students can communicate both with the staff and their peers. The aim is to support and facilitate the whole range of educational activities within a remote electronic environment.

Education, Distance↗

Analysis of first-pass and delayed contrast-enhancement patterns of dysfunctional myocardium on MR imaging: use in the prediction of myocardial viability.

OBJECTIVE: The purpose of the study was to analyze first-pass and delayed contrast-enhancement patterns of dysfunctional myocardial regions on MR imaging after injection of gadopentetate dimeglumine to predict myocardial viability in patients with coronary artery disease. SUBJECTS AND METHODS: Twelve patients with wall motion abnormalities and related coronary artery disease revealed by conventional coronary angiography underwent MR imaging at 1.5-T before and 3 months after revascularization therapy. Short-axis images were acquired using a cine gradient-echo sequence. Each slice was divided into eight segments. Overall, 73 segments with impaired contractility were imaged during the first-pass and 14 +/- 2 min after injection of 0.05-mmol/kg gadopentetate dimeglumine at a flow of 3 ml/sec using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as the criterion of viability. RESULTS: At study entry, 26 dysfunctional segments showed delayed hyperenhancement compared with the adjacent functional segments within the same slice, and 47 did not reveal hyperenhancement. After revascularization, 25 (96%) of the 26 hyperenhanced segments did not recover function, whereas 39 (83%) of the 47 segments without hyperenhancement showed mechanical improvement. Segment-related sensitivity and specificity for the correlation of lack of delayed hyperenhancement with myocardial viability were 39 (98%) of 40 and 25 (76%) of 33, respectively. Hypoenhancement during first-pass did not serve as a reliable criterion of viability. CONCLUSION: Evidence of delayed hyperenhancement of dysfunctional myocardium may be used to predict lack of mechanical improvement or nonviability, whereas the lack of hyperenhancement can be correlated with improvement of regional contractility or viability after revascularization.

Aged↗

Pentostatin (Nipent) and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with previously untreated, treated, and fludarabine-refractory B-cell chronic lymphocytic leukemia.

Renewed interest in chronic lymphocytic leukemia (CLL) has led to an unprecedented number of investigators contributing to all aspects of research in this disease. In fact, the evolution of research in the area of molecular aberrations in CLL and their impact on treatment resistance alone is striking. These data, along with the advent of the purine analogs, have been central to this paradigm shift. The inferior response rate, the abbreviated response duration, and the inability to prolong survival with alkylating agents such as chlorambucil have resulted in purine analogs being used as first- and second-line therapy for patients with CLL. In fact, patients treated with fludarabine have a higher overall and complete response rate as well as a disease-free survival advantage compared with patients treated with alkylator-based therapy. Pentostatin, the first purine analog to enter clinical trials, was never subjected to extensive schedule optimization despite its demonstrated efficacy and its paucity of significant myelosuppression compared with the other purine analogs. However, pentostatin induced a 25% to 30% response rate in heavily pretreated CLL patients, including some who had received prior fludarabine, suggesting possible non-cross-resistance. Based on preclinical data demonstrating synergistic activity when a DNA damaging agent (eg, an alkylating agent) is followed by an inhibitor of DNA repair (a purine analog), a number of purine analog/alkylator combinations have been and are presently being examined in a variety of lymphoid neoplasms. While the clinical data conflict, at least two phase II studies examining a combination of a purine analog and an alkylator in untreated patients with CLL have generated promising data. This report describes the scientific justification and the design of a new phase II study examining the combination of pentostatin and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with untreated, treated, and fludarabine-refractory B-cell CLL.

Antibiotics, Antineoplastic↗

1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.

After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1, 3-dihydroimidazol-2-yl)piperidine 8. Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot" procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1, 3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or 5-position of the 1, 3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater selectivity (>1000-fold) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has >1000-fold selectivity over all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D(4) receptor.

Animals↗

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.

Adenosine Triphosphate↗

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Adult↗

Cine MR imaging after myocardial infarction--assessment and follow-up of regional and global left ventricular function.

Myocardial infarction often leads to regional wall motion defects and in case of large defects to remodeling of the left ventricle. With this study, changes in regional and global myocardial function of 12 patients 3 weeks after myocardial infarction and after revascularization therapy were determined using MRI. Cine MRI was performed at study entry at rest and during low-dose dobutamine stimulation. All patients were re-examined at rest 3 and 6 months after the revascularization, including analysis of wall thickening and of left ventricular end-diastolic volume index (LVEDVI), end-systolic volume index (LVESVI), ejection fraction (LVEF), and mass index. After revascularization. 6 patients with stress-induced improvement of regional wall thickening recovered, 4 patients without improvement did not, but 2 patients without stress-induced improvement of wall thickening also recovered. Concerning global cardiac function, patients with mainly improved regional wall motion also showed a lower LVESVI and a higher LVEF than patients without improvement of regional contractility 6 months after revascularization in comparison to study entry. In conclusion, improvement of global myocardial function after revascularization is higher in patients with improved contractility in the infarcted region. The extent of the response of regions with wall motion defects to dobutamine stress correlates with the actual improvement after revascularization, and, therefore, dobutamine stress MRI may be helpful in selecting patients that will have a higher benefit from a revascularization therapy.

Adult↗

Cyclosporine-induced autologous graft-versus-host disease in patients with acute myeloid leukemia undergoing non-myeloablative chemotherapy without progenitor cell reinfusion.

To determine the incidence and severity of cyclosporine-induced graft-versus-host disease following non-myeloablative chemotherapy without progenitor cell reinfusion in patients with acute leukemia, 17 adults with refractory acute myeloid leukemia (14) or blastic phase of chronic myeloid leukemia (3) were treated with etoposide 2400 mg/m2 and cyclophosphamide 120 mg/kg followed by cyclosporine (CsA) 2.5 mg/kg i.v. daily and interferon gamma 0.025 mg/m2 subcutaneously every other day until day 28. Skin biopsies were obtained on days 14 and 28, or on the appearance of a skin rash, and graded for GVHD. Blood samples were examined at baseline and weekly starting on day 14 for natural killer (NK) cell and T cell lymphocytic changes. Post-treatment lymphocytes from select patients were assessed for allogeneic NK cell and autologous leukemic cell cytolytic activity. Four patients developed pathologic grade 2 cutaneous acute GVHD. Of the three patients who achieved a complete remission, two had evidence of GVHD. Post-treatment, three patients (two with GVHD) in whom adequate numbers of lymphocytes could be obtained showed NK cell cytolytic activity against allogeneic tumor cells (K562), but none had cytolytic activity against their own cryopreserved leukemic cells. These data suggest that in patients with AML treated with subablative doses of chemotherapy without autotransplant, autologous GVHD can be induced, although at an incidence lower than that reported for CsA-induced GVHD following marrow transplantation. An enhancement of T cell and NK cell activity levels similar to experiences in syngeneic models of autologous GVHD was seen, but no direct autologous leukemic cell cytotoxicity could be demonstrated.

Adult↗

[CINE-MRT for the study of the effects of regional left ventricular wall motion disorders on global heart function after a myocardial infarct and revascularization].

PURPOSE: To determine changes in global cardiac function and mass caused by infarct-associated regional wall motion abnormalities and to compare the changes after revascularization in patients with and without improvement of regional contractility. MATERIALS AND METHODS: 21 patients with regional left ventricular wall motion abnormalities and associated coronary artery stenoses requiring revascularization were examined with a Cine FLASH-2D sequence 26 +/- 12 days after their first myocardial infarction and re-examined three months after revascularization. Regional contractility and volumes and masses of both ventricles were determined. RESULTS: After revascularization, regional wall motion improvement led to decreased left ventricular volumes and improved ejection fractions, whereas patients with persisting wall motion defects showed unchanged left ventricular functional parameters. Comparing both groups of patients, the patients with improvement of regional contractility revealed lower end-systolic volumes and higher ejection fractions at follow-up. Cardiac masses and right ventricular parameters were not different, patients with a depressed right ventricular ejection fraction showed improvement at follow-up. DISCUSSION: After myocardial infarction, revascularization of the infarct-related coronary artery leads to an improvement of left ventricular function only if there is also an improvement of regional contractility. An effect on right ventricular function was not observed three months after the first small- or middle-sized myocardial infarction.

Adult↗

[The quantification of energy-rich phosphates in healthy and damaged heart muscle by SLOOP 31P-MR spectroscopy. Spatial localization with optimal pointspread function].

PURPOSE: A quantitative 31P-MR-spectroscopic technique was used to assess the energy metabolism in healthy and diseased myocardium. METHODS: 31P spectra were acquired on a 1.5 T scanner using a 3D-chemical shift imaging technique. Based on the anatomical information provided by 1H images, SLOOP (Spatial Localization with Optimal Pointspread Function) allows to obtain spectra from defined compartments. With SLOOP a free voxel shape with adaption to anatomic structures, e.g. the myocardium, is possible. Absolute values for phosphocreatine (PCr) and adenosine triphosphate (ATP) were determined using an external standard. RESULTS: 31P-spectra showed only minimal contamination by surrounding tissue. The standard deviation for the determined values of healthy volunteers was low. Compared to healthy volunteers, reduced PCr and ATP concentrations were seen for dilative cardiomyopathies and coronary artery disease and unchanged concentrations were observed for hypertensive heart disease. CONCLUSION: 31P-MR spectroscopy with SLOOP allows a non-invasive, quantitative analysis of cardiac energy metabolism.

Adenosine Triphosphate↗

[3-dimensional MR coronary angiography in the navigator technic for the primary diagnosis of coronary heart disease: a comparison with conventional coronary angiography].

PURPOSE: Evaluation of three-dimensional MR coronary angiography with the navigator technique for the primary diagnosis of coronary artery disease (CAD) in patients with chest pain. MATERIALS AND METHODS: In this prospective study 20 patients with chest pain were examined with MR coronary angiography and conventional angiography. The three-dimensional MR coronary angiography was performed using a 1.5 T scanner with an ECG-triggered 3D-FLASH-sequence and retrospective respiratory gating in the navigator technique. The MR coronary angiography was evaluated by two radiologists blinded to the results of the conventional coronary angiography. RESULTS: One patient was excluded from further evaluation due to reduced image quality. Conventional coronary angiography excluded CAD in 8/19 patients, 11/19 patients overall showed 20 stenoses (> 50%) or occlusions. With MR coronary angiography, CAD was correctly excluded in 7 patients, one patient was false positive, one patient was false negative. 14/20 stenoses (> 50%) or occlusions were detected, 5 stenoses were diagnosed false positive. Sensitivity and specificity for primary diagnosis of CAD or detection of coronary artery stenoses were 91% and 88% or 70% and 91%, respectively. DISCUSSION: Using MR coronary angiography with the navigator technique in the primary evaluation of CAD, the diagnosis of stenoses or occlusions of the main coronary arteries is feasible.

Adult↗

Three-dimensional MR coronary angiography using the navigator technique compared with conventional coronary angiography.

OBJECTIVE: We evaluated the diagnostic accuracy of three-dimensional (3D) MR coronary angiography with the navigator technique for the detection of coronary artery stenoses in comparison with that of conventional radiographic angiography. SUBJECTS AND METHODS: Thirty patients with coronary artery disease were examined with an ECG-triggered 3D fast low-angle shot sequence using retrospective respiratory gating and the navigator technique on a 1.5-T MR scanner. The data set was evaluated as a 3D view with a surface rendering technique. RESULTS: Imaging of the proximal coronary arteries was possible in all patients. The average visualized lengths of the left main, left anterior descending, left circumflex, and right coronary arteries were 1.9+/-0.5 cm (mean +/- SD), 5.2+/-2.3 cm, 4.2+/-1.9 cm, and 5.2+/-2.5 cm, respectively. Irregular breathing reduced image quality in seven of the 30 patients, making diagnosis of stenoses impossible. In the 77% of patients whose examinations resulted in high-quality images, the sensitivity and specificity for detection of significant stenoses and occlusions in all four main coronary arteries were 81% and 89%, respectively. CONCLUSION: The navigator technique allows reproducible imaging of the proximal course of coronary arteries. This technique obviates breath-hold studies, thus allowing more patients to be examined. In patients whose examinations resulted in high-quality images, significant coronary artery lesions could be seen. However, for widespread clinical use, further technical improvement is necessary to increase sensitivity and specificity.

Adult↗

[Selection of BVDV genotype II isolates using a monoclonal antibody and FACS analysis].

The infection of cattle with the bovine viral diarrhea virus (BVDV) in Germany is gaining attention and guidelines for the "protection of cattle farms against BVDV infections" were passed in 1997. New investigations about the damages induced by BVDV infections as well as the new occurrence of so-called BVDV genotypes (BVDV I and II) made the problems to become aware. The newly described BVDV genotype considerably differs both genetically and antigenetically from the up to now known BVD-viruses (BVDV I). The subdivision in BVDV genotypes I and II is based on genomic differences, which are determined by sequence analyses of different parts of the viral genome. Here, we describe the classification of BVDV in genotypes using a monoclonal antibody and indirect immunofluorescence with flow cytometry (FACS) based analysis. The suitability of the mab WB160 (Central Veterinary Laboratory, Weybridge; UK) for the classification of both BVDV-genotypes was first checked using genetically defined BVDV isolates. While all BVDV I isolates (n = 20) reacted with high fluorescence signals, the mab WB160 could not detect any of the defined BVDV II isolates (n = 20). Subsequently, 505 BVDV field strains isolated between 1993-1997 were screened for both genotypes using the mab WB160 and FACS analysis. 33 (6.5%) of the BVDV isolates were classified as BVDV II.

Animals↗