Plasma membrane disruption underlies injury of the corneal endothelium by ultrasound

The nature and the extent of acute injury to corneal endothelial cells caused by exposure to ultrasound radiation were characterized, as well as the long-term reaction of these cells to this form of injury. It was found that the degree of lethal cell injury induced by ultrasound scaled with exposure intensity and duration. Immediate changes in plasma membrane permeability were induced by ultrasound exposure. This ultrasound-induced permeability change was, however, transient in many cells, allowing them to trap and retain a normally impermeant tracer, fluorescein dextran, in cytosol. Microvilli were present on ultrasound treated cells in far greater density than on control cells, characteristic of exocytosis-based resealing. Cultures containing a majority of transiently permeabilized endothelial cells were morphologically indistinguishable from untreated control cultures, and the fluorescein dextran-labeled cells in these populations locomoted and divided normally. We conclude that cell death due to ultrasound exposure can occur rapidly via a necrotic mechanism that can be attributed to mechanically induced damage to the plasma membrane. However, not all cells injured become necrotic: some survive and appear to behave normally after exposure. Conditions that favor plasma membrane disruption resealing, e.g. that result in sub-lethal rather than lethal cell injury, may mitigate the reduction in corneal endothelial cell density consequent on phacoemulsification and aspiration surgery.     

Scientific validation of two commercial pressure sensor systems for prosthetic socket fit

The concept of measuring pressure at the interface between the stump and the prosthetic socket could provide valuable information in the process of prosthetic socket fabrication, modification, and fit. Two systems, the Rincoe Socket Fitting System (SFS) and Tekscan's F-Socket Pressure Measurement System, have been commercially designed for in situ interface pressure measurement over the past decade. Their use is not common in prosthetic practice, perhaps due to questions of cost effectiveness and the difficulties of interpreting the data. Another concern is the use of sensors for pressure measurements in areas of high contour and complex geometries such as the stump. Before these systems can be used in a clinical setting, it is necessary to determine the reliability and accuracy of each system. In order to assess the clinical validity of the Rincoe SFS and F-Socket systems, a series of trials was conducted to evaluate different aspects of sensor performance, namely; accuracy, hysteresis, drift and the effect of curvature. The sensors were subjected to tests in flatbed and custom-designed pressure vessels. Overall results indicated an accuracy error for the Rincoe SFS system of 25% (flatbed) and 33% (mould), with a corresponding 15% (flatbed) and 23% (mould) error in hysteresis, and 7% (flatbed) and 11% (mould) drift errors. The F-Socket system demonstrated an 8% (flatbed) and 11% (mould) accuracy errors, 42% (flatbed) and 24% (mould) hysteresis errors, and 12% (flatbed) and 33% (mould) drift errors. These findings indicate favourable results for the F-Socket Pressure Measurement System compared to the Rincoe Socket Fitting System with respect to its accuracy errors only. Nevertheless, it is the authors' belief that these systems are adequate in indicating areas of high pressure at the stump socket interface for clinical purposes, but both systems should be used with caution.     

A preliminary investigation into the use of virtual environments in memory retraining after vascular brain injury: indications for future strategy?

Purpose: In a preliminary investigation of the use of Virtual Environments (VEs) in neurorehabilitation, this study compares the effects of active and passive experience of a VE on two types of memory in vascular brain injury patients and controls. Method: Forty-eight patients with vascular brain injury and 48 non-impaired control participants were randomly assigned to active and passive VE conditions. The active participants explored a virtual bungalow seeking a particular object; the passive participants observed, but did not control movement through the VE, also seeking the object. Afterwards, both active and passive participants completed spatial recognition and object recognition tests. Results: Expectedly, the patients were impaired relative to the controls but were able to perform the virtual tasks. Active participation in the VE enhanced memory for its spatial layout in both patients and controls. On object recognition, active and passive patients performed similarly, but passive controls performed better than active controls. Conclusions: The findings are discussed in relation to their implications for memory rehabilitation strategies.     

Reversal of ethanol and indomethacin-induced suppression of hepatic DNA synthesis by 16,16-dimethyl prostaglandin E2

Investigations were undertaken to determine effectiveness of 16,16-dimethyl prostaglandin E2 (dmPGE2) in overcoming the suppressive effects of ethanol and/or indomethacin on hepatic DNA synthesis. Adult litter mate Sprague-Dawley rats were subjected to sham operation or partial hepatectomy. Immediately after partial hepatectomy, and at 8-hr intervals for 24 hr, the rats were given: (a) ethanol with and without dmPGE2 or (b) indomethacin with and without ethanol and/or dmPGE2. DmPGE2 produced a significant increase in DNA synthesis in sham-operated (p less than 0.001) and untreated partially hepatectomized animals (p less than 0.025). Ethanol and indomethacin caused a 6- and 18-fold reduction, respectively, in hepatic DNA synthesis following partial hepatectomy. DmPGE2 overcame the inhibitory effect of ethanol (p less than 0.005) and indomethacin (p less than 0.0005) in partially hepatectomized animals. Mitoses were decreased concomitantly with ethanol and/or indomethacin-induced reduction in DNA synthesis and increased with administration of dmPGE2. It is concluded that dmPGE2 increases hepatic DNA synthesis and regeneration in normal rat liver and overcomes their inhibition when ethanol and/or indomethacin is given after partial hepatectomy. Timing of dmPGE2 administration is crucial. When given 30 min before ethanol, it completely inhibits suppression of regenerative activity; omission of this "priming" dmPGE2 dose results in only 44% of DNA synthesis obtained in control animals.     

Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage

BACKGROUND: We have shown in a previous work that HBOC-201 is able to reverse anaerobic metabolism at low volumes in a porcine model of controlled hemorrhage. On the basis of these results, we hypothesize that low-volume resuscitation with HBOC-201 in a porcine model of controlled hemorrhage provides adequate tissue oxygenation to limit end-organ damage and allow for survival of the animal. METHODS: Twenty-four Yorkshire swine (55-65 kg) were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and then divided into four groups. The first group, Shed Blood (BL), was resuscitated with shed blood to baseline MAP. A second group, Shed Blood (60), underwent resuscitation for four hours at an MAP of 60 mm Hg with shed blood. The third group, LR + Blood, was resuscitated with lactated Ringer's (maximum, 40 mL/kg) followed by shed blood to baseline MAP. The final group, HBOC (60), underwent resuscitation for 4 hours at an MAP of 60 mm Hg with HBOC-201. Hemodynamic variables, urine output, blood gas analyses, lactate levels, and jejunal oximetry were followed throughout the experiment. Animals were allowed to survive and underwent necropsy on postinjury day 3. Histologic comparisons were made. Data were analyzed using analysis of variance/Duncan's multiple range test. RESULTS: All animals survived the hemorrhage/resuscitation. One animal in the LR + Blood group died on postinjury day 1. Heart rate, MAP, and arterial pH were similar between groups. Cardiac output was significantly lower throughout resuscitation in the HBOC (60) group. Jejunal oximetry was similar throughout the experiment in all groups, revealing a decline in Po2 during hemorrhage and return to baseline or near baseline during resuscitation. There was no evidence of renal dysfunction. Histologically, one animal in the LR + Blood group and four of six animals in the HBOC (60) group demonstrated mild hepatocellular damage. All other tissues examined were found to have no significant abnormalities. Elevations in serum aspartate aminotransferase levels were noted when comparing the HBOC (60) group to the Shed Blood (BL) and Shed Blood (60) groups on day 2. Significant decreases in hemoglobin levels were noted in the HBOC (60) group compared with all other groups beginning on day 2. CONCLUSION: Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.     

Totally laparoscopic aortobifemoral bypass: a review of 22 cases

OBJECTIVE: Laparoscopic aortobifemoral bypass (LABF) has been performed for diffuse aortoiliac occlusive disease in a few large centers. We hypothesize that in selected patients LABF can be performed safely and is a viable, minimally invasive approach to aortoiliac occlusive disease. METHODS: We conducted a retrospective review of all individuals undergoing LABF over a 2.5-year period in a community-based vascular surgery practice. RESULTS: From January 2002 to August 2004, LABF was performed successfully in 20 of 22 patients. The age of the patients ranged from 49 to 75 years, with 11 male and 11 female subjects. LABF required a median duration of 267 minutes (range, 199 to 365 minutes) to complete. Median aortic cross-clamp time was 89.5 minutes (range, 64 to 14 minutes) with an aortic anastomotic time of 37 minutes (range, 30 to 56 minutes). Blood loss averaged 0.69 +/- 0.081 L. Median intensive care stay was 1 day, and hospital stay was 4 days. The median duration of postoperative intravenous narcotics via patient-controlled analgesia pump was 2 days. No patients received epidural analgesia. Nearly all patients began a liquid diet 1 day and a solid diet 4 days after surgery. Complications occurred early in our experience and included one death secondary to mesenteric infarction possibly caused by excessive visceral traction. There was one pelvic abscess, one ureteral injury, and two limb occlusions necessitating thrombectomy and revision. The last six patients had uneventful operative procedures and recoveries. Of the two LABF failures, one patient required open conversion because of inadequate aortic exposure and the other required a short upper midline incision to complete the aortic anastomosis. Compared with conventional open aortobifemoral bypasses performed concomitantly during this period, selected LABF patients required fewer narcotics, experienced less bowel dysfunction, and were discharged home sooner. CONCLUSIONS: Aortobifemoral bypass can be performed through a minimally invasive laparoscopic approach. Although technically demanding with a steep learning curve, experience should reduce the significant complication rate. Compared with a conventional open aortobifemoral bypass, advantages include less pain, minimal postoperative bowel dysfunction, and a shorter hospital stay.     

Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial

Context  Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. Objective  To determine the immunogenicity of a novel tetravalent CRM₁₉₇-conjugated meningococcal vaccine (MenACWY) in infants. Design, Setting, and Participants  Randomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006. Intervention  UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Main Outcome Measure  Percentage of infants with a human complement serum bactericidal activity (hSBA) titer 1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed. Results  According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers 1:4 after primary immunization were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%); C, 98% (93%-99%); W-135, 99% (94%-100%); and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers 1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers 1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients; a temperature of 38°C or greater was observed in 4% and 2% in these groups, respectively. Conclusion  MenACWY is well tolerated and immunogenic in infancy. Trial Registration  clinicaltrials.gov Identifier: NCT00262002