Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate—Rapid Tumor Regression Documented by Real Time 3D Echocardiography

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.     

Alternating repetition time balanced steady state free precession.

A novel balanced SSFP technique for the separation or suppression of different resonance frequencies (e.g., fat suppression) is presented. The method is based on applying two alternating and different repetition times, TR(1) and TR(2). This RF scheme manipulates the sensitivity of balanced SSFP to off-resonance effects by a modification of the frequency response profile. Starting from a general approach, an optimally broadened stopband within the frequency response function is designed. This is achieved with a TR(2) being one third of TR(1) and an RF-pulse phase increment of 90 degrees . With this approach TR(2) is too short ( approximately 1 ms) to switch imaging gradients and is only used to change the frequency sensitivity. Without a significant change of the spectral position of the stopband, TR(1) can be varied over a range of values ( approximately 2.5-4.5 ms) while TR(2) and phase cycling is kept constant. On-resonance spins show a magnetization behavior similar to balanced SSFP, but with maximal magnetization at flip angles about 10 degrees lower than in balanced SSFP. The total scan time is increased by about 30% compared to conventional balanced SSFP. The new technique was applied on phantoms and volunteers to produce rapid, fat suppressed images.     

Contrast behavior and relaxation effects of conventional and hyperecho-turbo spin echo sequences at 1.5 and 3 T.

To overcome specific absorption rate (SAR) limitations of spin-echo-based MR imaging techniques, especially at (ultra) high fields, rapid acquisition relaxation enhancement/TSE (turbo spin echo)/fast spin echo sequences in combination with constant or variable low flip angles such as hyperechoes and TRAPS (hyperTSE) have been introduced. Due to the multiple spin echo and stimulated echo pathways involved in the signal formation, the contrast behavior of such sequences depends on both T2 and T1 relaxation times. In this work, constant and various variable flip angle sequences were analyzed in a volunteer study. It is demonstrated that a single effective echo time parameter TE(eff) can be calculated that accurately describes the overall T2 weighted image contrast. TE(eff) can be determined by means of the extended phase graph concept and is practically independent of field strength. Using the described formalism, the contrast of any TSE sequence can be predicted. HyperTSE sequences are demonstrated to show a robust and well-defined T2 contrast allowing clinical routine MRI to be performed with SAR reductions of typically at least 70%.     

Wissenschaftliche Neurobildgebung in der Medizin

Neuroimaging has in recent years greatly contributed to our understanding of a wide range of aspects of central neurological diseases. These include the classification and localization of disease (e.g., in headache), the understanding of pathology (e.g., in Parkinson’s disease), mechanisms of reorganization (e.g., in stroke), and the subclinical progress of disease (e.g., in degenerative diseases). Apart form presurgical mapping, clinical applications of fMRI are limited. However, functional imaging enables the formulation of neurobiological hypotheses that can be tested clinically and is suited to test classical clinical hypotheses about how the brain works. Understanding the mechanisms and the site of pathology, e.g., in cluster headaches, will lead and has led to new therapeutic strategies. New methodological developments for neuroscientific applications are aimed at the integration of functional and morphological connectivity through a combination of magnetic resonance techniques (fMRI, DTI) and electrophysiological (EEG, MEG) recordings. In addition to stimulus-dependent activations, resting state activity has found increasing interest, for example, in sleep research and various psychiatric diseases (e.g., schizophrenia, borderline).     

Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy.

The absolute concentrations of the three major brain metabolites observable by in vivo proton spectroscopy--N-acetylaspartate(NAA), creatine and phosphocreatine (Cr and PCr) and choline (Cho)--have been measured at four standardized localizations in 34 healthy volunteers by in vivo localized proton spectroscopy using an external reference sample. The results show that the concentration of Cr and PCr as observed by in vivo MRS (5-6 mmol/L) is lower than that measured by other methods. The results are concordant with the hypothesis, that the Cr and PCr resonance as observed by proton spectroscopy is due mainly to PCr, whereas Cr remains invisible by being attached to a larger molecule. It is also demonstrated, that Cr and PCr is higher in the cerebellum than in the cerebrum, whereas NAA remains constant within the margin of error (8-9 mmol/L).     

The biomechanics of restricted movement in adult obesity

In spite of significant advances in the knowledge and understanding of the multi-factorial nature of obesity, many questions regarding the specific consequences of the disease remain unanswered. In particular, there is a relative dearth of information pertaining to the functional limitations imposed by overweight and obesity. The limited number of studies to date have mainly focused on the effect of obesity on the temporospatial characteristics of walking, plantar foot pressures, muscular strength and, to a lesser extent, postural balance. Collectively, these studies have implied that the functional limitations imposed by the additional loading of the locomotor system in obesity result in aberrant mechanics and the potential for musculoskeletal injury. Despite the greater prevalence of musculoskeletal disorders in the obese, there has been surprisingly little empirical investigation pertaining to the biomechanics of activities of daily living or into the mechanical and neuromuscular factors that may predispose the obese to injury. A better appreciation of the implications of increased levels of body adiposity on the movement capabilities of the obese would afford a greater opportunity to provide meaningful support in preventing, treating and managing the condition and its sequelae. Moreover, there is an urgent need to establish the physical consequences of continued repetitive loading of major structures of the body, particularly of the lower limbs in the obese, during the diverse range of activities of daily living.     

Protein expression of MMP-13, uPA, and PAI-1 in pseudocapsular and interface tissue around implants of loose artificial hip joints and in osteoarthritis

Matrix metalloproteinase 13 (MMP-13), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1) have been reported to be involved in aseptic loosening of artificial hip joints. This study for the first time presents the protein levels of all of these factors in synovial-like interfaces between bone and prosthesis and in pseudocapsular tissues surrounding the artificial joint in patients with aseptic loosening (n=17) measured by ELISA. No differences were observed in the antigen expression of MMP-13, uPA, and PAI-1, comparing interface and pseudocapsular tissue. Also, no significant correlation between the protein expression of these factors and years from arthroplasty to revision or to type of fixation (cemented vs. cementless) was observed. As control, MMP-13, uPA, and PAI-1 antigen levels were also determined in the synovium of patients with osteoarthritis (n=10). Yet, the antigen levels of MMP-13, uPA, and PAI-1 in tissue specimens from patients with aseptic loosening of artificial hip joints were significantly higher compared to their expression in synovial capsular tissues obtained from patients with osteoarthritis. In conclusion, this study shows that elevated protein levels of uPA, PAI-1, and MMP-13 in periprosthetic pseudocapsular and interface tissues from patients after total hip replacement due to aseptic loosening seem not to be associated with the patient outcome.     

Isolation of DNA from the centromere of human chromosome 7 by microdissection

Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a micro-dissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3–4 cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.This revised version was published online in November 2005 with corrections to the Cover Date.     

Outcome of patients with ventricular assist devices and acute renal failure requiring renal replacement therapy

The significance of acute renal failure (ARF) for patients treated with a ventricular assist device (VAD) is uncertain. There is little information on the outcome of patients who require renal replacement therapy during treatment with a VAD. A retrospective review was undertaken to evaluate the impact of renal failure requiring renal replacement therapy on such patients. Studied were 227 patients who were supplied with a VAD at the German Heart Institute Berlin. Fifty-five patients required renal replacement therapy during treatment with a VAD. These were compared with patients not needing renal replacement therapy (ARF and non-ARF groups). Significant differences for the end points of survival, heart transplantation, and discharge from hospital were observed in patients with ARF (p < 0.01). Survival was then analyzed according to indications for treatment with a VAD (bridge to transplantation or cardiac recovery after cardiotomy, transplantation, myocardial infarction, myocarditis, and endocarditis). Survival for bridge-to-transplantation patients was clearly influenced in a negative way by ARF (p < 0.01). For cardiac recovery patients, only a small difference in survival was observed (p = 0.05). We conclude that ARF is a negative predictor for bridge-to-transplantation patients. For cardiac recovery patients the impact of ARF on survival is marginally significant.