Biomedical subjects

William B Stewart

Publications and source records attributed to William B Stewart.

7 recordsLinked to original sources

PubMed2006

Should we continue teaching anatomy by dissection when ...?

The central role that human dissection has long held in clinical education is being reevaluated in many institutions. Despite the impression that many institutions are abandoning dissection, very few have and most of those have reinstated dissection within a few years. What are the inherent qualities that lead institutions back to dissection? In our efforts to redesign a shortened dissection course, our consultations with a broad range of clinicians lead us to understand how the rhythms of clinical practice are modeled and developed in the small-group setting of the dissection laboratory. Following further consultation with colleagues who have experimented with different models of anatomy instruction, we discuss three themes in support of dissection. First, problem-solving in the dissection laboratory develops the habits-of-mind of clinical practice. Second, relating dissection to imaging modalities develops the spatial reasoning skills needed to understand computer simulations, interpret imaging data, and interact with surgeons, radiologists, and patients. Third, the human face of dissection fosters self-reflection and integration of the cognitive and affective skills required for medical practice. Through group process, the collaborative effort of dissection teams develops essential of attributes of clinical professionalism.

Anatomy↗

PubMed2006

Design principles for developing an efficient clinical anatomy course.

The exponential growth of medical knowledge presents a challenge for the medical school curriculum. Because anatomy is traditionally a long course, it is an attractive target to reduce course hours, yet designing courses that produce students with less understanding of human anatomy is not a viable option. Faced with the challenge of teaching more anatomy with less time, we set out to understand how students employ instructional media to learn anatomy inside and outside of the classroom. We developed a series of pilot programs to explore how students learn anatomy and, in particular, how they combine instructional technology with more traditional classroom and laboratory-based learning. We then integrated what we learned with principles of effective instruction to design a course that makes the most efficient use of students' in-class and out-of-class learning. Overall, we concluded that our new anatomy course needed to focus on transforming how medical students think, reason, and learn. We are currently testing the hypothesis that this novel approach will enhance the ability of students to recall and expand their base of anatomical knowledge throughout their medical school training and beyond.

Anatomy↗

PubMed2004

Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity.

Premature human infants frequently suffer from periventricular leukomalacia (PVL) characterized by the loss of central myelinated tracts in the brain [Neuropathology, 22 (2002) 193]. Rodent chronic sublethal hypoxia (CSH) from P3 to 33 (postnatal day 3-33) provides a model for PVL characterized by cerebral ventriculomegaly and reductions in cerebral white matter volume [Brain Res. Dev. Brain Res. 111 (1998) 197; Proc. Natl. Acad. Sci. USA 100 (2003) 11718]. Here, we demonstrate that mice exposed to CSH from P3 to P33 followed by normoxia from P33 to P75 continue to exhibit a locomotor hyperactivity that resembles behavioral changes observed in some human children with very low birth weights. Because periventricular white matter is specifically lost in PVL, we examined the expression of oligodendrocyte proteins. Hypoxic rearing dramatically decreases the level of the axon outgrowth inhibitor Nogo-A in oligodendrocytes of CNS white matter at P12. The Nogo-A decrease exceeds the moderate decrease in another myelin protein, myelin associated glycoprotein (MAG). Although myelin protein expression returns to normal by maturity (P75), persistent abnormalities in axonal trajectories are detectable. Anterograde axonal tracing from motor cortex demonstrates ectopic corticofugal fibers in the corticospinal tract (CST), corpus callosum, and caudate nucleus of adult animals reared in CSH. Thus, hypoxia-induced reduction in myelin-derived axon outgrowth inhibitors appears to contribute axonal misconnection to the pathology of very low birth weight infants.

Age Factors↗

PubMed2004

Chronic neonatal hypoxia leads to long term decreases in the volume and cell number of the rat cerebral cortex.

Preterm birth results in significant neurodevelopmental disability. The neonatal rodent model of chronic sublethal hypoxia faithfully mimics the effect of preterm birth on the developing brain. We employed this model to test the hypothesis that the hypoxia that accompanies preterm birth results in inappropriate signaling of apoptotic mechanisms in developing brain. We performed cortical cell counts, determinations of neuronal size and Western analyses of the apoptosis related proteins, Bcl-2 and Bax, in rat pups who were raised in chronic hypoxia (FiO2 9.5%) beginning on postnatal day 3 (P3) and extending for either 10 (P13) or 30 (P33) days. A third group of animals was exposed to 30 days of hypoxia followed by an additional 30 days in a normoxic environment (P63) to assess the potential for recovery from the initial effects of hypoxia. Age matched control pups were raised in room air throughout the experimental time period. Assessment of cortical cell number revealed a 25% reduction (P < 0.01) in total cell number following 30 days of hypoxic rearing. Glia were significantly reduced by 34% and 41% after 10 and 30 days of hypoxia, respectively, while neuron numbers were only significantly reduced (14%) after 30 days of hypoxia. Animals exposed to a hypoxic environment for 30 days followed by 30 days in a normoxic environment revealed some recovery of glial cell numbers, but no significant recovery of neuronal cell numbers. Measurement of cell size at both P13 and P33 revealed that neurons of layer III were significantly smaller in cross-sectional area in hypoxic compared with control rats (P < 0.01). However, no significant difference was noted in neuronal size following 30 days of normoxic recovery. Western blot analyses of Bcl-2 and Bax protein levels demonstrated a ratio favorable to Bax at multiple time points during the period of hypoxic exposure. These data suggest that chronic exposure to hypoxia during the perinatal period alters the production and maintenance of glial and neuronal cells and that glia and neurons demonstrate differential patterns of vulnerability and recovery following subsequent periods of normoxic exposure. It is hypothesized that the mechanisms responsible for these alterations in cortical cell number may depend on the state of differentiation of the different cell types at the time of hypoxic exposure.

Animals↗

PubMed2002

Disrupted synaptic development in the hypoxic newborn brain.

Infants born prematurely risk significant life-long cognitive disability, representing a major pediatric health crisis. The neuropathology of this cohort is accurately modeled in mice subjected to sublethal postnatal hypoxia. Massively parallel transcriptome analysis using cDNA microchips (9,262 genes), combined with immunohistochemical and protein assays, reveals that sublethal hypoxia accentuates genes subserving presynaptic function, and it suppresses genes involved with synaptic maturation, postsynaptic function, and neurotransmission. Other significantly affected pathways include those involved with glial maturation, vasculogenesis, and components of the cortical and microtubular cytoskeleton. These patterns reveal a global dysynchrony in the maturation programs of the hypoxic developing brain, and offer insights into the vulnerabilities of processes that guide early postnatal cerebral maturation.

Animals↗

PubMed2002

Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system.

Recent data have demonstrated that vascular endothelial growth factor (VEGF) is expressed by subsets of neurons, coincident with angiogenesis within the developing cerebral cortex. Here we investigate the characteristics of VEGF expression by neurons and test the hypothesis that VEGF may serve both paracrine and autocrine functions in the developing central nervous system. To begin to address these questions, we assayed expression of VEGF and one of its potential receptors, Flk-1 (VEGFR-2), in the embryonic mouse forebrain and embryonic cortical neurons grown in vitro. Both VEGF and Flk-1 are present in subsets of post-mitotic neurons in vivo and in vitro. Moreover, VEGF levels are up-regulated in neuronal cultures subjected to hypoxia, consistent with our previous results in vivo. While the abundance of Flk-1 is unaffected by hypoxia, the receptor exhibits a higher level of tyrosine phosphorylation, as do downstream signaling kinases, including extracellular signal-regulated protein kinase, p90RSK and STAT3a, demonstrating activation of the VEGF pathway. These same signaling components also exhibited higher tyrosine phosphorylation levels in response to exogenous addition of rVEGFA(165). This activation was diminished in the presence of specific inhibitors of Flk-1 function and agents that sequester VEGF, resulting in a dose-dependent increase in apoptosis in these neuronal cultures. Further, inhibition of MEK resulted in increased apoptosis, while inhibition of phosphatidylinositol 3-kinase had no appreciable affect. In addition to the novel function for VEGF that we describe in neuronal survival, neuronal VEGF also affected the organization and differentiation of brain endothelial cells in a three-dimensional culture paradigm, consistent with its more traditional role as a vascular agent. Thus, our in vitro data support a role for neuronal VEGF in both paracrine and autocrine signaling in the maintenance of neurons and endothelia in the central nervous system.

Animals↗

PubMed2002

Correlation of Web usage and exam performance in a human anatomy and development course.

Course materials for a Human Anatomy and Development Course were placed on the World Wide Web (WWW). The materials included a lab manual, lecture notes and slides, faculty-generated atlases, Web links, and examinations. The lab manual, lecture notes, and atlases were also provided as black-and-white hardcopy. The Office of Education assigned students a code name that allowed them to use the Web site and take exams anonymously. Student Web use was tracked and correlated with their performance on the final examination. Overall use patterns revealed that most students used the Web site to prepare for examinations, but not for daily studying. Old examinations were the most accessed documents; lecture notes were the least accessed. The access patterns of the students with top 20, middle 20 (closest to the mean), and bottom 20 scores on the final examination were compared. In general, there was little difference between the middle and top groups. Students in the bottom group used computer resources significantly less than the other groups. In a second analysis, the 10 students who used the Web site most frequently scored below the mean. The study suggests that interactive exercises will be heavily used, but that the preparation of all course materials for the WWW may not be an efficient use of institutional resources.

Achievement↗