Effects of ossein-hydroxyapatite compound on ewe bone remodeling: Biochemical and histomorphometric study

Summary Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.     

Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions

Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail.     

Prediction of volume responsiveness using pleth variability index in patients undergoing cardiac surgery after cardiopulmonary bypass

Background

The pleth variability index (PVI) is derived from analysis of the plethysmographic curve and is considered to be a noninvasive parameter for prediction of volume responsiveness. The aim of our prospective clinical study was to evaluate if volume responsiveness can be predicted by PVI in patients undergoing cardiac surgery after cardiopulmonary bypass.

Methods

Eighteen patients were prospectively studied. Directly after cardiac surgery, PVI, stroke volume variation (SVV), and cardiac index (CI) were recorded. Colloid infusion (4?ml/kg body weight) was used for volume loading, and volume responsiveness was defined as increase of CI more than 10?%.

Results

SVV and PVI measures were found to be highly correlated at r?=?0.80 (p?<?0.001). Receiver operating characteristics curve (ROC) analysis resulted in an area under the curve of 0.87 for SVV and 0.95 for PVI, which values did not differ statistically significant from each other (p?>?0.05). The optimal threshold value given by ROC analysis was ≥11?% for SVV with a sensitivity and specificity of 100?% and 72.2?%. For PVI, optimal threshold value was ≥16?% with a sensitivity and specificity of 100?% and 88.9?%. Positive and negative predictive values estimating an increase of CI ≥10?% for SVV were 44.4?% and 100?% and 66.7?% and 100?% for PVI.

Conclusions

For consideration of fluid responsiveness PVI is as accurate as SVV in patients after cardiopulmonary bypass. Methodological limitations such as instable cardiac rhythm after cardiopulmonary bypass and right- or left ventricular impairment seem to be responsible for low specificity and positive predictive values in both parameters PVI and SVV.     

Transcatheter Valve-in-Valve Therapies: Patient Selection, Prosthesis Assessment and Selection, Results, and Future Directions

The development of transcatheter valve implantations (TAVI) has induced profound changes in the treatment of valvular heart disease over the past decade. At the same time, due to excellent clinical results, bioprostheses continuously outperformed mechanical prostheses. The increasing number of elderly patients has led to numerous patients presenting with deteriorated bioprostheses needing reoperation. In selected high-risk patients or patients with unreasonable surgical risk, valve-in-valve TAVI has advanced to a viable alternative to conventional redo surgery. High procedural success, good hemodynamics and acceptable clinical results were reported up until now. Valve-in-valve TAVI seems to be safe and effective in treatment of deteriorated valve prostheses in high-risk patients. The valve-in-valve concept presents the next step toward an individual treatment strategy for patients at prohibitive risk for conventional surgery. Present studies were reviewed with special concern to patient selection, prosthesis assessment, device selection, clinical outcome and technical challenging aspects as well.     

Molecular ontogeny of donor-derived follicular lymphomas occurring after hematopoietic cell transplantation

The relative timing of genetic alterations that contribute to follicular lymphoma remains unknown. We analyzed a donor-recipient pair who both developed grade 2/3A follicular lymphoma 7 years after allogeneic transplantation and donor lymphocyte infusions. Both patients harbored identical BCL2/IGH rearrangements also present in 1 in 2,000 cells in the donor lymphocyte infusion, and the same V(D)J rearrangement, which underwent somatic hypermutation both before and after clonal divergence. Exome sequencing of both follicular lymphomas identified 15 shared mutations, of which 14 (including alterations in EP300 and KLHL6) were recovered from the donor lymphocyte infusion by ultra-deep sequencing (average read coverage, 361,723), indicating acquisition at least 7 years before clinical presentation. Six additional mutations were present in only one follicular lymphoma and not the donor lymphocyte infusion, including an ARID1A premature stop, indicating later acquisition during clonal divergence. Thus, ultrasensitive sequencing can map clonal evolution within rare subpopulations during human lymphomagenesis in vivo. SIGNIFICANCE: For the first time, we define the molecular ontogeny of follicular lymphoma during clonal evolution in vivo. By using ultrasensitive mutation detection, we mapped the time-course of somatic alterations after passage of a malignant ancestor by hematopoietic cell transplantation.     

A numerical simulation of intranasal air temperature during inspiration

OBJECTIVES/HYPOTHESIS: In vivo measurements of the intranasal air temperature are feasible. The present study was designed to reproduce temperature distributions within the human nasal cavity by means of numerical simulation. STUDY DESIGN: Numerical simulation. METHODS: Based on computed tomography (CT), a steady-state computational fluid dynamics (CFD) simulation was performed displaying the temperature distribution throughout the human nasal cavity during inspiration. The results of the numerical simulation were compared with in vivo temperature measurements. RESULTS: The numerical simulation demonstrated that the major increase of the inspiratory air temperature can be found in the anterior nasal segment, especially within the nasal valve area, which is comparable to in vivo measurements. Intranasal areas of high temperature were characterized by turbulent airflow with vortices of low velocity. The results of numerical simulation showed an excellent comparability to the results of previous in vivo measurements in the entire nasal cavity. CONCLUSION: The anterior nasal segment is the most effective part of the nose in heating of the ambient air. The findings demonstrated the complexity of the relationship between airflow patterns and heating of inspired air. A numerical simulation of the temperature distribution using CFD is practicable.