Fatal encephalitis in a patient with refractory celiac disease presenting with myorhythmia and carpal spasm.

We report the case of a woman with refractory celiac disease who developed abnormal spontaneous movements of the extremities and face consistent with myorhythmia. Investigation led to a diagnosis of encephalitis, confirmed by postmortem examination. The movements were likely caused by nonparaneoplastic encephalitis associated with refractory celiac disease. Etiologic and diagnostic considerations and treatment options are discussed.     

The Island Pedicle Flap

Background. Surgical defects following the extirpation of cutaneous neoplasia may present challenges to the dermatologic surgeon. There are many repair options for an individual defect, including second-intention healing, primary closure, skin graft, and skin flap closure. The island pedicle flap is a random pattern advancement flap well suited to reconstruct a variety of small- to intermediate-sized soft tissue wounds.
Objective. To review the utility of the island pedicle flap in reconstructive dermatologic surgery and to detail the operative technique to achieve reproducible functional and esthetic results.
Methods. The method of flap reconstruction is presented. A variety of defects repaired with this technique are reviewed.
Results. The subcutaneous island pedicle flap yielded excellent functional and cosmetic repair of the presented defects with minimal operative morbidity. Secondary to a well-preserved central vascular pedicle, complications are infrequent.
Conclusions. The random pattern island pedicle flap is a versatile and robust flap used to repair a variety of soft tissue wounds in a single-stage procedure with reproducible operative outcomes.     

Effect of endothelium mimicking self-assembled nanomatrices on cell adhesion and spreading of human endothelial cells and smooth muscle cells

The goal of this study is to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles (PAs) through a solvent evaporation technique. Three PAs, one containing the Tyr-Ile-Gly-Ser-Arg (YIGSR) ligand, the second containing the Val-Ala-Pro-Gly (VAPG) ligand, and a third without cell adhesive ligands, were developed. Cell adhesion and spreading were evaluated by a PicoGreen-DNA assay and live/dead assay, respectively. Our results show that PA-YIGSR significantly enhances HUVEC adhesion (26,704 ± 2708), spreading (84 ± 8%), and proliferation (50 ± 2%) compared with that of other PAs. PA-VAPG and PA-YIGSR showed significantly greater AoSMC adhesion compared with that of PA-S. PA-VAPG also showed significantly greater spreading of AoSMCs (63 ± 11%) compared with that of other PAs. Also, all the PAs showed significantly reduced platelet adhesion compared with that of collagen I (control). These findings would facilitate the development of novel vascular grafts, heart valves, and cell-based therapies for cardiovascular diseases.From the Clinical EditorThe goal of this study was to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles through a solvent evaporation technique. The findings are expected to facilitate the development of novel vascular grafts, heart valves, and cell based therapies for cardiovascular diseases.     

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

Is commercial alcohol availability related to adolescent alcohol sources and alcohol use? Findings from a multi-level study.

PURPOSE: To examine whether compliance with underage sales laws by licensed retail establishments is related to underage use of commercial and social alcohol sources, perceived ease of obtaining alcohol, and alcohol use. METHODS: In 2005, alcohol purchase surveys were conducted at 403 off-premise licensed retail establishments in 43 Oregon school districts. A survey also was administered to 3,332 11th graders in the districts. Multi-level logistic regression analyses were used to examine relationships between the school district-level alcohol sales rate and students' use of commercial and social alcohol sources, perceived ease of obtaining alcohol, past-30-day alcohol use, and heavy drinking. RESULTS: The school district-level alcohol sales rate was positively related to students' use of commercial alcohol sources and perceived alcohol availability, but was not directly associated with use of social alcohol sources and drinking behaviors. Additional analyses indicated stronger associations between drinking behaviors and use of social alcohol sources relative to other predictors. These analyses also provided support for an indirect association between the school district-level alcohol sales rate and alcohol use behaviors. CONCLUSIONS: Compliance with underage alcohol sales laws by licensed retail establishments may affect underage alcohol use indirectly, through its effect on underage use of commercial alcohol sources and perceived ease of obtaining alcohol. However, use of social alcohol sources is more strongly related to underage drinking than use of commercial alcohol sources and perceived ease of obtaining alcohol.     

An optimal regulator for linear systems with multiple state and input delays

This paper presents an optimal regulator for a linear system with multiple state and input delays and a quadratic criterion. The optimal regulator equations are obtained reducing the original problem to the linear‐quadratic regulator design for a system without delays. Performance of the obtained optimal regulator is verified in the illustrative example against the best linear regulators available for the linear system without delays and for two rational approximations of the original time‐delay system. Simulation graphs demonstrating better performance of the obtained optimal regulator with respect to the criterion value are included. Copyright © 2006 John Wiley & Sons, Ltd.     

Calcineurin B1 is essential for positive but not negative selection during thymocyte development

During development, discrete cell fates often result from variation in the intensity of a particular signal. The mechanisms underlying these seemingly analog-to-digital switches are not understood. In developing T lymphocytes, low-intensity signals through the antigen receptor result in positive selection while more intense signals give rise to negative selection. By deleting the genetic locus encoding the regulatory B1 subunit of calcineurin specifically in thymocytes, we found an absolute requirement for calcineurin in positive selection. In contrast, calcineurin activity was dispensable in several models of negative selection. Unexpectedly, we found that removal of calcineurin activity from thymocytes results in inefficient ERK activation at the double-positive stage of thymocyte development, when selection occurs. These studies clarify the mechanism by which graded signals are converted to discrete outcomes in T cell development and further indicate that the developmental roles of calcineurin likely contribute to immunosuppression by calcineurin inhibitors.     

Effects of increasing osmolality on rat ileal smooth muscle

The effects of changing bathing medium osmolality on tension generation in smooth muscle were studied on potassium-depolarized segments of rat ileum. Increasing the tonicity of the medium evokes a transient relaxation of the smooth muscle; restoration of isotonicity evokes a transient contraction of similar amplitude and time course. While immersed in hypertonic media of less than 1.3 times normal tonicity, the smooth muscle slowly increases its isometric tension; in media of nearly twice normal tonicity, the smooth muscle loses tension. All of these effects occur whether the medium is made hypertonic with added NaCl or sucrose.     

The Clinical Health Economics System Simulation (CHESS): a teaching tool for systems- and practice-based learning.

Academic medical centers face barriers to training physicians in systems- and practice-based learning competencies needed to function in the changing health care environment. To address these problems, at the University of Virginia School of Medicine the authors developed the Clinical Health Economics System Simulation (CHESS), a computerized team-based quasi-competitive simulator to teach the principles and practical application of health economics. CHESS simulates treatment costs to patients and society as well as physician reimbursement. It is scenario based with residents grouped into three teams, each team playing CHESS using differing (fee-for-service or capitated) reimbursement models. Teams view scenarios and select from two or three treatment options that are medically justifiable yet have different potential cost implications. CHESS displays physician reimbursement and patient and societal costs for each scenario as well as costs and income summarized across all scenarios extrapolated to a physician's entire patient panel. The learners are asked to explain these findings and may change treatment options and other variables such as panel size and case mix to conduct sensitivity analyses in real time. Evaluations completed in 2003 by 68 (94%) CHESS resident and faculty participants at 19 U.S. residency programs preferred CHESS to a traditional lecture-and-discussion format to learn about medical decision making, physician reimbursement, patient costs, and societal costs. Ninety-eight percent reported increased knowledge of health economics after viewing the simulation. CHESS demonstrates the potential of computer simulation to teach health economics and other key elements of practice- and systems-based competencies.