Large-Displacement Vertical Electrostatic Microactuator Dynamics using Duty-Cycled Softening/Stiffening Parametric Resonance.

Electrostatic microactuators with large vertical scanning range (several hundred microns) at high frequency (hundreds to thousands of hertz) and chips sizes compatible with endoscopic microscopy have recently been demonstrated based on parametric resonance. This paper examines the use and modeling of mixed softening/hardening dynamics to help produce large ranges of motion in this class of mirrors. Origin of spring stiffening behavior in actuator design is described, followed by non-dimensional analysis of actuator motion trends. Experimental results are presented for a sample actuator design with up to 480 µm displacement at 1225 Hz and 60 V. Comparison to predicted trends and comments on benefits and limitations of modeling are provided.

Widespread Distribution of Fungivorus Aphelenchoides spp. in Blight Cankers on American Chestnut Trees.

Previously we showed in laboratory studies that the fungivorus nematode, Aphelenchoides hylurgi, was attracted to and fed upon the chestnut blight fungus, Cryphonectria parasitica, from American chestnut bark cankers and was a carrier of biocontrol, white hypovirulent C. parasitica strains. In the present field study, we recovered Aphelenchoides spp. in almost all (97.0 %) of 133 blight canker tissue assays (three 5-g samples each) from four eastern states. High mean population densities (227 to 474 nematodes per 5 g tissue) of Aphelenchoides spp. were recovered from cankers in Virginia, West Virginia, and Tennessee but not from New Hampshire (mean = 75 nematodes per 5 g tissue). Overall, most canker assays yielded population densities less than 200 nematodes per 5 g tissue. All of 12 very small or young cankers yielded a few to many Aphelenchoides spp. Regression analysis indicated greatest recovery of Aphelenchoides spp. occurred in the month of May (r = 0.94). The results indicate that Aphelenchoides spp. appear to be widespread in blight cankers on American chestnut trees and could play a role in biocontrol of chestnut blight.

Amplifying transmission and compact suspension for a low-profile, large-displacement piezoelectric actuator.

A low-profile, piezoelectrically-driven microactuator is presented that achieves very large stroke lengths within size constraints suitable for certain endoscopic microscopy applications. The actuator utilizes a transmission consisting of lever arm and chevron-beam structures to amplify high-force, low-displacement motion of a ceramic lead-zirconate-titanate (PZT) brick into large displacement of a translational platform. For ±120 V input, a full range of 486 µm of motion is achieved, with natural frequency greater than 500 Hz. This corresponds to an anticipated In addition, the lateral translational platform is supported by a redesign of common folded silicon flexures to provide large transverse and vertical stiffness when the width of the actuator is limited.

Acute abdominal symptoms and signs in children and young adults with spina bifida: ten years' experience.

BACKGROUND/PURPOSE: Diagnosis and management of the acute abdomen in patients with spina bifida (SB) can be problematic. There are at least 4 clinical factors that can predispose to the development of acute abdominal symptoms and signs, and patients with a thoracic level lesion can have a partially insensate abdomen. The authors analyzed their accumulated experience to determine the annual incidence of acute abdominal signs and symptoms in children and young adults with spina bifida, the differential diagnosis, the operative management, and the outcome. The pertinent literature was reviewed. METHODS: Cases were ascertained during a 10-year period at 1 institution and reviewed retrospectively. RESULTS: Twenty-two episodes of acute abdominal symptoms and signs in 19 children and young adults with SB were ascertained over 10 years at 1 institution, for an annual incidence of 0.74%. More patients had a thoracic level lesion (n = 12; 60%) than in the clinic population as a whole (27%; P =.04), but the gender distribution was similar (58% girls), as was the prevalence of ventriculoperitoneal shunts (VPS; 95%). The median age was 13 years (range, 1 year to 26 years). Hospitalization was necessary for 19 (86%) of the 22 episodes. The duration of symptoms before diagnosis was a median of 3 days (range, 1 to 14 days). Most patients (82%) presented with abdominal pain. Fever was present in 27%, shock in 23%, and peritoneal signs in 23%. There were 14 different final diagnoses, 10 (71%) of which were associated with a predisposing factor. Of the 22 episodes, 18 (82%) could be attributed to an underlying factor: (1) neurogenic bladder (9; 41%); (2) neurogenic bowel (3; 14%); (3) VPS (4; 18%); (4) complications from previous surgery (2; 9%). Thirteen patients (59%) underwent a total of 20 surgical procedures of 12 different kinds. Despite awareness of the complexities involved, 3 patients (14%) died: 1 from complications resulting from bladder perforation; 1 from urosepsis and shock; and 1 from peritonitis caused by VPS infection. CONCLUSION: The differential diagnosis of the acute abdomen in patients with SB is broad, conditions requiring surgery are frequently diagnosed, and the mortality rate is substantial, despite aggressive management.

Attenuated expression of inducible nitric oxide synthase in lung microvascular endothelial cells is associated with an increase in ICAM-1 expression.

BACKGROUND/PURPOSE: The molecular and cellular events that regulate inflammatory lung injury, a major cause of morbidity in surgical patients, remain unclear. The authors hypothesize that nitric oxide (NO) plays an important role in regulating polymorphonuclear cell (PMN)-induced acute lung injury, and further, that attenuated expression of inducible nitric oxide synthase (iNOS) and therefore decreased production of NO by lung microvascular endothelial cells (LMVEC), accelerates inflammation and injury. METHODS: LMVEC and aortic EC (AEC) from rat and human were stimulated with lipopolysaccharide (LPS) and cytokines; changes in iNOS mRNA expression and iNOS activity were determined. The role of NO in mediating inflammatory responses was evaluated by determining PMN adherence to LMVEC and lung tissue slices in the presence and absence of NOS inhibitors and NO donors. Human LMVEC and AEC were assessed by FACS analysis for ICAM-1 expression, because this is thought to be a critical determinant of PMN adherence. RESULTS: When stimulated with endotoxin and cytokines, rat AEC monolayers express nearly 3-fold more iNOS mRNA than rat LMVEC. The low levels of LMVEC iNOS expression are associated with a 4-fold lower nitrite and nitrate production. Similar trends are seen in human endothelial cells. When iNOS activity was blocked, PMN adherence to tumor necrosis factor alpha (TNFalpha)/LPS-stimulated LMVEC was markedly increased. In contrast, adding a nitric oxide donor to endotoxin/cytokine-stimulated LMVEC monolayers reduced PMN adherence to near background levels. Similar responses were observed in vivo. Human lung microvascular endothelial cells show a substantially increased level of ICAM-1 upregulation when compared with similarly stimulated human aortic macrovascular endothelial cells. CONCLUSIONS: These data indicate that LMVEC express less iNOS and produce less NO than AEC. This lower expression and activity of iNOS in LMVEC may be linked to increased expression of ICAM-1. Because ICAM-1 has been shown to be essential for tight PMN adherence, these data suggest that relatively low iNOS expression in LMVEC may contribute to a propensity for the lung to be injured by activated PMNs.

An experimental evaluation of cyclic voltammetry of multicharged species at macrodisk electrodes in the absence of added supporting electrolyte.

The reversible reduction of [S2Mo18O62]4- to [S2Mo18O62]5- and [S2Mo18O62]6- at a glassy carbon macrodisk electrode has been studied by cyclic voltammetry in acetonitrile as a function of the concentration of [(C6H13)4N]4[S2Mo18O62] in the absence and presence of [(C6H13)4N]ClO4 as the added supporting electrolyte. Consideration is given to the influence of scan rate, reference-working electrode distance, [(C6H13)4N]4[S2Mo18O62], and electrolyte concentrations. Experimental data confirm theoretical predictions that cyclic voltammetry at a macrodisk electrode is a viable technique for studies of multiply charged electroactive species without added electrolyte, provided the influence of enhanced complexities associated with effects of increased solution resistance, the mass transport contribution from migration, and convection arising from enhanced density gradients are considered. Enhanced density gradients present in the absence of added supporting electrolyte give rise to a more marked dependence of voltammograms on the angle of the electrode and hence lead to significant distortion of wave shapes at low scan rates. The summation of all these obstacles implies that quantitative evaluation of cyclic voltammograms of multiply charged species requires significantly greater care in the absence than in the presence of added supporting electrolyte.

Uncompensated resistance. 1. The effect of cell geometry.

The meaning and significance of uncompensated resistance are carefully explained. Many factors influence the uncompensated resistance and several of these are explored in this article, using idealized models of an electrochemical cell. Among the factors whose roles have been elucidated are the shape and size of the cell, the location of the reference electrode, the shape of the working electrode, and the size and position of the counter electrode. Worthwhile compensation is shown to be impossible with microelectrodes.

Concentrations of Electroactive Solutes, during Cyclic and Other Voltammetries, at Points Away from the Electrode Surface. 1. Fundamental Relationships and Their Validation.

There are circumstances in which it is useful to know the concentration, or its gradient, of an electroactive product or reactant at some distance from an electrode. Here it is demonstrated that this information is available, in principle, under conditions of semiinfinite planar diffusion, provided that the surface concentration and/or the current are known as functions of time. Several methods of calculation are explored, using the example of linear sweep voltammetry. Some of these methods rely on analytical formulations; others are purely numerical. Concordance of the results of the various methods provides validation of all. A method based on the convolution of the current is especially versatile.

Oxidative stress in critical care: is antioxidant supplementation beneficial?

Reactive oxygen species (ROS) are constantly produced in human beings under normal circumstances. Antioxidant systems help defend the body against ROS but may be overwhelmed during periods of oxidative stress, which can cause lipid peroxidation, damage to DNA, and cell death. Critical illness, such as sepsis or adult respiratory distress syndrome, can drastically increase the production of ROS and lead to oxidative stress. Sources of oxidative stress during critical illness include activation of the phagocytic cells of the immune system (the respiratory burst), the production of nitric oxide by the vascular endothelium, the release of iron and copper ions and metalloproteins, and the vascular damage caused by ischemia reperfusion. Only indirect measurements of ROS are available, but the presence of oxidative stress in critical illness is supported by clinical studies. In general, serum antioxidant vitamin concentrations seem to decrease and measures of oxidative stress seem to increase in critically ill populations. Oxidative stress has been associated with sepsis, shock, a need for mechanical ventilation, organ dysfunction, acute respiratory distress syndrome, disseminated intravascular coagulation, surgery, and the presence of an acute-phase response. In addition, higher levels of oxidative stress seem to occur in patients with more notable injuries. Dietary supplementation with antioxidant vitamins seems to be the logical answer to decreasing serum antioxidant concentrations, but antioxidants may have adverse effects. The benefit of supplementing antioxidants in critically ill populations has not been shown and requires further study.

Successful surgical outcome in children with sickle hemoglobinopathies: the Duke University experience.

BACKGROUND/PURPOSE: Surgery in patients with sickle hemoglobinopathies can be problematic because of the potential for sickling events in the perioperative and postoperative period. The authors and others have previously reported successful surgical outcomes using an aggressive erythrocyte transfusion regimen, designed to alleviate anemia and to reduce the percentage of sickle hemoglobin to below 30%. Recently, a randomized trial compared this aggressive regimen with a more conservative transfusion regimen and found no differences in perioperative complications. The incidence of complications, however, was very high in each group (31% to 35%). METHODS: The authors therefore analyzed retrospectively their surgical experience in children with sickle hemoglobinopathies over the past 10 years to determine the efficacy of an aggressive transfusion regimen and skilled perioperative care in their patient population. RESULTS: A total of 130 surgical procedures were performed on 92 children including 54 cholecystectomies (42%), 23 splenectomies (18%), 12 ENT procedures (9%), 11 central line placements and removals (8%), 7 herniorrhaphies (5%), 7 appendectomies (5%), and 16 miscellaneous operations (13%). The mean age of the children was 10 years (range, 1 to 22 years), and the mean weight was 32.1 kg (range, 9.9 to 76.8 kg). The average hemoglobin (mean +/- 1 SD) at the time of surgery was 11.2+/-1.3 g/dL, and the average percent hemoglobin S was 21+/-11%. CONCLUSIONS: Relatively few transfusions were required to achieve these endpoints, and the complications resulting from transfusions were minimal. Similarly, the number of perioperative and postoperative events was very low.

Differential nitric oxide production by microvascular and macrovascular endothelial cells.

Phenotypic heterogeneity among endothelial cell populations may account for important organ-specific behaviors. Experimental evidence suggests that endothelium-derived nitric oxide mediates certain of these unique responses. The purpose of these investigations was to compare rat pulmonary microvascular endothelial cells with pulmonary artery and aortic macrovascular endothelial cells in their ability to generate nitric oxide (NO). Cultures of these microvascular and macrovascular endothelial cells were incubated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and Salmonella typhimurium lipopolysaccharide (LPS) alone or in combination, and nitrite production was measured. Single-agent exposure with IFN-gamma (up to 1,000 U/ml), TNF-alpha (up to 60,000 U/ml), or LPS (up to 500 ng/ml) had little effect on nitrite generation. Nitrite production by rat aortic macrovascular endothelial cells (RAEC) was significantly greater than that by the rat lung microvascular endothelial cells (RLMVEC) when stimulated with TNF-alpha + IFN-gamma, LPS + IFN-gamma, or TNF-alpha + LPS. The maximal response by all endothelial cell types (approximately 15-fold increase in RAEC and 8-fold increase in RLMVEC) was observed with LPS + IFN-gamma. The nitrite generation from rat pulmonary artery endothelial cells was intermediate between RAEC and RLMVEC responses when stimulated with IFN-gamma + LPS or TNF-alpha. Similar patterns of heterogeneous inducible nitric oxide synthase mRNA induction occurred when Northern analysis of specimens from the cultured endothelial cell types was done. These data suggest that phenotypic heterogeneity between these endothelial cell populations is substantial and, by inference, that site-specific NO. generation may occur.

Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus.

Transplantation of cultured postnatal human thymus was performed in a patient with complete DiGeorge syndrome. Biopsy of the graft 3 mo after implantation revealed normal CD1+ thymocytes in thymic cortical epithelial regions and CD1- thymocytes in thymic medullary epithelial regions, respectively. HLA analysis of graft thymocyte and thymic microenvironment components demonstrated that developing thymocytes and thymic macrophages were recipient derived, while thymic epithelial components were of donor origin. The patient, who initially had no T cells and had profoundly defective T cell function, developed normal T cell responses to mitogens and Ags, tolerance to donor in a mixed lymphocyte reaction, and normal Ab titers after tetanus toxoid and pneumovax immunization. Thus, transplantation of cultured postnatal human thymic tissue in humans can form functional chimeric thymic tissue, and may provide a strategy to reconstitute the peripheral T cell pool in select congenital and acquired immune deficiency syndromes.

Limiting Currents for Steady-State Electrolysis of an Equilibrium Mixture, with and without Supporting Inert Electrolyte.

An exact treatment derives the steady-state limiting current of a one-electron reduction for the N ⇌ O(+) + A(-) mixture at a hemispherical microelectrode. Either or both of the neutral N and cationic O(+) species may be electroactive. A supporting salt is present at any concentration, including zero or excess; its ions are electropassive and do not interact with the other solutes or each other. The various species are treated as having distinct diffusivities, linked to their mobilities through the Nernst-Einstein relationship. Universal electroneutrality is assumed. The predictions of the model are compared with published experimental data on the reduction of aqueous weak acids; agreement is excellent at intermediate, but poor at low, support ratios. Analysis of the unsupported case shows that the neutral N species dissociates in a narrow zone close to the electrode, and the injection of ions there serves to increase the electric field in the outer region of the transport zone. This enhances cationic migration enormously, leading to an unsupported limiting current that is much more than double the supported value. However, the limiting current is drastically diminished by traces of foreign electrolyte. Curiously, the limiting current with full support adopts the same value when equilibration is fast as when it is very slow, although the mechanisms are totally different.

The effect of intestinal reperfusion on renal function and perfusion.

This study examines the effect of intestinal reperfusion injury (IIR) on renal blood flow and relates this temporally to changes in renal ATP levels and renal tubular function. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IIR). Renal blood flow was measured with radiolabeled microspheres and a Doppler flow probe. Renal dysfunction was quantitated by measuring inulin clearance and fractional excretion of sodium (FENa) in the isolated perfused organ. Renal tissue ATP levels were measured using a luciferase-luciferin assay. Sham-operated animals served as controls (SHAM). Renal blood flow was reduced by > 80% in the animals sustaining IIR when compared to baseline measurements (P < 0.05) or SHAM (P < 0.05). Temporally this reduction in renal blood flow was associated with a 25% reduction in tissue ATP levels (P < 0.05). The kidneys of animals sustaining IIR had a significantly greater FENa than did those of controls. These data support the notion that IIR is associated with a profound reduction in renal blood flow which is temporally related to reduced renal tissue ATP levels and renal tubular dysfunction.

Hepatic hypoperfusion after intestinal reperfusion.

BACKGROUND: Intestinal ischemia-reperfusion injury (IIR) induces hepatic and pulmonary dysfunction and thus has been used as a model of multiple organ failure syndrome. This study examines the hypothesis that hepatic blood flow is markedly reduced in this injury model. METHODS: Sprague-Dawley rats underwent 120 minutes of intestinal ischemia and 60 minutes of reperfusion (IIR). Hepatic blood flow was measured with radiolabeled microspheres and Doppler flow probes. Hepatic dysfunction was quantitated by measuring bile flow and serum alanine aminotransferase and hepatic tissue adenosine triphosphate levels. Sham-operated animals served as controls. RESULTS: Intestinal ischemia reduced portal flow by 66% when compared with sham-operated animals (p = 0.0001) but had no effect on hepatic arterial flow. In contrast, reperfusion reduced hepatic artery flow by 80% when compared with controls (p = 0.002) with most of this change occurring within 5 minutes of reperfusion. IIR induced a 63% reduction in bile flow (p < 0.05), a fivefold rise in serum alanine aminotransferase level (p < 0.0002), and a 33% reduction in hepatic adenosine triphosphate level (p < 0.05). CONCLUSIONS: These data suggest that IIR induces profound hepatic hypoperfusion, which is temporally related to acute hepatic dysfunction. This observation suggests that hepatic ischemia may contribute to IIR-induced liver injury.

Effect of diffusion coefficient diversity on steady-state voltammetry when homogeneous equilibria and migration are encountered.

An exact treatment is developed to predict the steady-state limiting voltammetric current, I(L), for a system in which the reaction O(+) + A(-) ⇆ N occurs reversibly in solution, in the presence of supporting electrolyte C(+)A(-). Either or both O(+) and N undergo a one-electron reduction at the hemispherical microelectrode. The dependence of I(L) on the formation constant of the equilibration reaction, the electrolyte concentration, and the support ratio is derived for any trio of values of these parameters and for any combination of diffusivities of the O(+), N, and A(-) species.

Splanchnic PGI2 release and "no reflow" following intestinal reperfusion.

This study examines the hypothesis that reduced splanchnic blood flow during intestinal reperfusion (IR) is associated with impaired release of the vasodilatory prostanoid PGI2. Sprague-Dawley rats underwent occlusion of the superior mesenteric artery (SMA) for 120 min and reperfusion for up to 60 min. SMA blood flow was measured by transonic flow probe and radiolabeled microspheres (141Ce and 103Ru). Sham-operated animals served as controls (SHAM). Splanchnic eicosanoid release was quantitated by measuring thromboxane B2 (TxB2, stable metabolite of TxA2), 6-keto-PGF1a (6-keto, stable metabolite of PGI2), and PGE2 within the portal vein (PV) and inferior vena cava (IVC) of animals sustaining IR and SHAM. SMA flow in IR animals was < 10% of baseline and 27% of SHAM when measured by transonic flow probe (8 +/- 2% and 29 +/- 3%, IR and SHAM, respectively, P < 0.05). Similar results were obtained when intestinal blood flow was measured with microspheres (0.33 +/- 0.12 vs 1.34 +/- 0.13 ml/min/g, IR vs SHAM, P < 0.05). The greatest change in IR-induced splanchnic eicosanoid release occurred with 6-keto. Following ischemia, 6-keto levels in the PV were twice those of SHAM (P < 0.05). Five minutes after reperfusion, PV 6-keto levels were 22 times those of controls (P < 0.05) and 4 times greater than those of the IVC (P < 0.05). By 60 min of reperfusion, levels of 6-keto were reduced to those in the IVC. These data support the hypothesis that splanchnic blood flow is critically reduced by severe IR.(ABSTRACT TRUNCATED AT 250 WORDS)