Steady-state free precession projection MRI as a potential alternative to the conventional chest X-ray in pediatric patients with suspected pneumonia

Magnetic resonance imaging of the lung tissue is thought to be hardly possible due to physical limitations especially the low proton density, susceptibility, and motion artifacts. The objective of our study was to evaluate and refine a very fast MR technique at a low field strength which overcomes the limitations in MR lung imaging. Thirty-five investigations were performed in 30 pediatric patients with suspected pneumonia. The MR investigations were performed in coronal slice orientation without cardiac or respiratory triggering in a low-field MR system. An optimized true fast imaging with steady precession sequence was applied. The MR images and the corresponding conventional chest radiographs were evaluated. The examination time per slice was 1.6 s. No motion artifacts could be observed. The signal-to-noise ratio for pulmonary parenchyma ranged from 4.9 to 7.1. All pathological findings of the chest X-ray images were correctly identified by the MRI (κ=0.82–0.85). Effusions as well as small pneumonic infiltrates were more precisely detected by the MRI investigation (κ=0.82) as compared with X-ray. Low-field projection MRI is a promising alternative to pediatric chest X-ray. Due to its short examination time, it overcomes the physical limits of usual MRI methods and provides comparable diagnostic information. Electronic Publication     

The hippocampus and contextual memory retrieval in Pavlovian conditioning

Several theories of hippocampal function have suggested a role for the hippocampus in contextual memory retrieval. However, these theories are based on studies using permanent pretraining lesions, which confound the role of the hippocampus in learning with its role in retrieval. We argue that an alternative methodology is required to assess the role of the hippocampus in memory retrieval processes. This alternative methodology involves temporary inactivation of the hippocampus in Pavlovian paradigms that lend themselves to an examination of retrieval. An example of this approach is considered in a Pavlovian fear-conditioning paradigm. We examined the influence of hippocampal inactivation on the context-specific expression of latent inhibition, a response decrement displayed when excitatory conditioning is preceded by non-reinforced presentations of a to-be-conditioned stimulus. Reversible inactivation of the dorsal hippocampus prior to retrieval testing eliminated the context-specific expression of latent inhibition. The nature of the hippocampal role in retrieval processes is discussed in the light of these data.     

Estrogen modulates sexually dimorphic contextual fear conditioning and hippocampal long-term potentiation (LTP) in rats(1)

The present study examined the role of ovarian steroids in contextual fear conditioning and hippocampal synaptic plasticity in female rats. In experiment 1, adult female rats were ovariectomized and submitted to contextual fear conditioning, a procedure in which rats received unsignaled footshock in a novel observation chamber; freezing behavior served as the measure of conditional fear. Ovariectomized female rats froze at levels comparable to male rats, both of which froze significantly more than sham-operated female rats. In experiment 2, estrogen replacement in ovariectomized female rats reduced fear conditioning to a level comparable to that of sham-operated females in experiment 1. In experiment 3, the influence of estrogen on the induction of long-term potentiation (LTP) at perforant path-dentate granule cell synapses in ovariectomized female rats was examined. Estrogen decreased both population spike LTP and EPSP-spike potentiation at perforant path synapses. Taken together, these experiments indicate that ovarian steroids regulate both sexually dimorphic behavior and hippocampal plasticity in a fear-conditioning paradigm.     

Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors

Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.     

Development and evaluation of an integrated musculoskeletal disease course for medical students

BACKGROUND: A recent survey of medical and surgical residents in the United States suggested that our current training of physicians may be inadequate to meet the increasing demand for diagnosis and treatment of musculoskeletal disorders. In response, we developed an integrated, multidisciplinary course to teach knowledge and skills related to musculoskeletal disease to second-year medical students. A three-year prospective outcomes study was conducted to evaluate the new course. METHODS: The primary outcomes that were studied during the first year of the new course were the gains in knowledge, changes in levels of confidence, and long-term retention of skills. Secondary outcomes consisted of student and faculty satisfaction. Ten-item pre-tests and post-tests covering core course concepts were administered to students. A matched-pairs t test was used to evaluate the difference between pre-test and post-test scores. Students were also asked to rate, on a 10-point scale, how much confidence they had in their ability to perform the musculoskeletal physical examination before and after the institution of the new curriculum. A general linear model analysis with post hoc pairwise comparisons (F test) was used to evaluate the changes in the confidence levels of the students. Also, a knee examination station was organized to compare students' scores before and after revision of the course. At the conclusion of the course, students rated each aspect of it on a scale of 1 to 5. Instructors were asked to rate the effectiveness of all elements of the course on the same scale. RESULTS: On the basis of student satisfaction and confidence and faculty satisfaction, the most effective changes in the curriculum were the introduction of a physical examination workshop and simulated clinical situations. Students' knowledge increased significantly (p < 0.001), and their level of confidence increased significantly in thirteen specifically targeted areas (p < 0.0001). On the end-of-the-year examination assessing retention of physical examination skills, the scores for the skills emphasized in the revised course increased significantly whereas the scores for a skill not emphasized in the course remained the same. Revisions made in the second and third years after implementation of the course expanded the more successful elements and further improved student ratings. CONCLUSIONS: Integration of the three clinical disciplines related to musculoskeletal disease--orthopaedics, rheumatology, and physical medicine and rehabilitation--resulted in a highly effective introductory course for second-year medical students. The heuristic strategy of introducing core content through lectures and workshops followed by small-group teaching sessions for practice with the new knowledge effectively increased students' knowledge, confidence, and satisfaction.     

Toward development of imaging modalities for islets after transplantation: insights from the National Institutes of Health Workshop on Beta Cell Imaging

BACKGROUND: Pancreatic islet transplantation can provide insulin independence and near normal glucose control in selected patients with type 1 diabetes mellitus. However, in most cases, achieving insulin independence necessitates the use of at least two donor pancreases per recipient and the rate of insulin independence may decline after transplantation. To better understand the fate of transplanted islets and the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed. METHODS: Recent advances in noninvasive imaging techniques such as magnetic resonance imaging, positron emission tomography, and other imaging modalities show great promise as potential tools to monitor islet number, mass, and function in the clinical setting. A recent international workshop, "Imaging the Pancreatic Beta Cell," sponsored by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation International focused on these emerging efforts to develop novel ways of imaging pancreatic beta cells in vivo. RESULTS: Potential clinically applicable techniques include the use of directed magnetic resonance contrast agents such as lanthanides (Ln(3+)) and manganese (Mn(2+)) or magnetic resonance imaging probes such as superparamagnetic iron oxide nanoparticles. Potential techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or d-mannoheptulose. Optical imaging techniques are also being used to evaluate various aspects of beta cell metabolism including intracellular Ca(2+) flux, glucokinase activity, and insulin granular exocytosis. CONCLUSIONS: The consensus among investigators at the imaging workshop was that an accurate and reproducible in vivo measure of functional islet mass is critically needed to further the strides that have been made in both islet transplantation and diabetes research as a whole. Such measures would potentially allow the assessment of islet engraftment and the early recognition of graft loss, leading to greater improvements in islet graft survival and function.