Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Ketamine and midazolam is an inappropriate preinduction combination in uncooperative children undergoing brief ambulatory procedures

BACKGROUND: We prospectively studied the effects of intramuscular (i.m.) ketamine alone, or combined with midazolam, on mask acceptance and recovery in young children who were uncooperative during induction of anaesthesia. METHODS: The Institutional Review Board (IRB) approval was obtained to study 80 children, 1-3 years, scheduled for bilateral myringotomies and tube insertion (BMT). Mask induction was attempted in all the children. Those who were uncooperative were randomly assigned to one of the four preinduction treatment groups: group I, ketamine 2 mg.kg(-1); group II, ketamine 2 mg.kg(-1) combined with midazolam 0.1 mg.kg(-1); group III, ketamine 2 mg.kg(-1) with midazolam 0.2 mg.kg(-1); or group IV, ketamine 1 mg.kg(-1) with midazolam 0.2 mg.kg(-1). Anaesthesia was continued with nitrous oxide and halothane by facemask. RESULTS: Children in all treatment groups achieved satisfactory sedation in less than 3 min following the administration of the preinduction drug(s). Compared with patients who received halothane induction (comparison group), the use of ketamine alone did not significantly (P > 0.0167, a Bonferroni corrected significance level) delay recovery and discharge times (18.8 +/- 2.5 and 82.5 +/- 30.7 min vs 12.6 +/- 4.6 and 81.0 +/- 33.8 min, P = 0.030 and P = 0.941, respectively). Patients who received ketamine/midazolam combinations, however, had significantly longer recovery and discharge times vs halothane (32.3 +/- 14.0 and 128.0 +/- 36.6 min, P = 0.001, P = 0.007, respectively). These times were so clinically unacceptable, that the study had to be terminated with only 17 patients receiving study drugs. CONCLUSIONS: It is concluded that ketamine/midazolam combination is not appropriate for preinduction of anaesthesia in paediatric ambulatory patients because of unacceptably prolonged recovery and delayed discharge times.     

Off-pump multivessel coronary artery surgery in high-risk patients

BACKGROUND: Coronary artery bypass surgery on cardiopulmonary bypass is associated with significant morbidity and mortality, which may be more marked in high-risk patients. We evaluated our results of off-pump coronary artery bypass (OPCAB) in high-risk patients with multivessel coronary artery disease and compared them with results in similar patients who underwent operation on cardiopulmonary bypass. METHODS: A total of 1,075 patients who underwent OPCAB between October 1996 and June 2001 and who had one or more of the following risk factors were included in the study: poor left ventricular function (EF < or = 30%), advanced age (> 70 years), left main stenosis, acute myocardial infarction, and redo coronary artery surgery. These patients were compared with 2,312 similar patients who underwent coronary artery bypass grafting on cardiopulmonary bypass during the same period. Preoperative risk factors, intraoperative variables, and postoperative results were analyzed and compared between two groups. RESULTS: The average number of grafts was 3.0 +/- 0.4 and 3.2 +/- 0.3 in the off-pump (OPCAB) and on-pump (CCAB) groups, respectively. Hospital mortality was 3.2% and 4.5% in OPCAB and CCAB groups respectively (p = 0.109). Perioperative myocardial infarction, requirement of inotropic agents, stroke, and renal dysfunction were comparable in two groups. Intubation time (19 +/- 5 vs 24 +/- 6 hours, p < 0.001), mean blood loss (362 +/- 53 vs 580 +/- 66 mL, p < 0.001), atrial fibrillation (14.3 vs 19.7%, p < 0.001), and prolonged ventilation (4.6 vs 7.6%, p = 0.002) were less in OPCAB group. Intensive care unit stay (20 +/- 8 hours) and hospital stay (6 +/- 3 days) were significantly less in the OPCAB group (p < 0.001). CONCLUSIONS: Off-pump coronary artery surgery can be safely performed in high-risk patients with multivessel coronary artery disease. Operative mortality is comparable to that associated with on-pump surgery, and avoidance of cardiopulmonary bypass is associated with reduced postoperative morbidity in these patients.     

Transplanted neural stem cells survive,differentiate, and improve neurological motor function after experimental traumatic brain injury

OBJECTIVE: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury. METHODS: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were reanesthetized and randomized to receive stereotactic injection of NSCs or control cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 3 and 12 weeks after transplantation. RESULTS: Brain-injured animals that received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers but not markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy). CONCLUSION: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.     

Attentional modulation of SSVEP power depends on the network tagged by the flicker frequency

Modulation of the steady-state visual evoked potential (SSVEP) by attention was studied in detail using 15 'tag' frequencies in the range of 2.5-20 Hz. The stimuli were two series of random disc search arrays superimposed on two concentric color-marked annuli respectively. Two series of arrays were updated independently; one updated at one fixed frequency (flicker) and the other updated randomly according to a white noise distribution (random broadband flicker, rbbf). On each trial, the observer was instructed to attend one annulus and to detect a target (a triangle) that occasionally appeared in a random disc array in the attended annulus. The SSVEP results show that the choice of flicker frequency selects which cortical network synchronizes to the flicker two distinct cortical networks showed different effects of attention. SSVEP power and the effects of attention on SSVEP power strongly depend on both flicker frequency and radial position of rbbf annulus. At flicker frequencies in the delta band (2-4 Hz), and in the upper alpha band (10-11 Hz), an occipital-frontal network appears to phase-lock to the flicker when attending to the flicker, increasing the magnitude of the SSVEP. At flicker frequencies in the lower alpha band (8-10 Hz), a global response to a peripheral flickering stimulus, that includes parietal cortex and posterior frontal cortex, has higher amplitude when attention is directed away from the flickering peripheral stimulus and towards a competing rbbf stimulus in the fovea. Increases in SSVEP power when attention is directed to peripheral flicker are always associated with increases in phase locking. By contrast, at frequencies in the lower alpha band, increases in SSVEP power when attention is directed away from the flicker and towards foveal stimuli are not associated with changes in phase-locking. Thus, whether attention to a flicker stimulus increases or decreases SSVEP amplitude and phase locking depends on which of two cortical networks, which have distinct spatial and dynamic properties, is selected by the flicker frequency.     

End-of-Skin Grafts in Syndactyly Release: Description of a New Flap for Web Space Resurfacing and Primary Closure of Finger Defects

Treatment of syndactyly necessitates creation of neo-web space and separation of fingers. Traditionally, this has been done by use of flaps taken from the dorsum; the resultant raw areas thus created have been managed by use of skin grafts. The classical teaching has been that the separated fingers will need skin graft as primary closure is not possible. The skin grafts have a tendency to contract and lead to finger flexion contractures and “creep” of the web space. We describe a flap based upon subcutaneous tissue in the web that is moved in a V–Y fashion to resurface the neo-web. The flap donor site can easily be closed primarily. The fingers are then separated; the subcutaneous fat is carefully removed from the finger flaps under magnification to allow primary closure of the finger defects. It has been possible to primarily close the donor site and fingers in all the patients. The procedure has been used in seven patients with 14 web releases. The age varied between 10 months to 3 years. The V–Y advancement flap based upon the subcutaneous pedicle in the region of the web allows adequate creation of a new web space. The careful de-fattening of skin flaps allows the separated fingers to be closed primarily.     

Cost-effectiveness Analysis for Technology Acquisition

Background

In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.

Methods

The present study analysed cost-effectiveness of an “In-house” magnetic resonance imaging (MRI) scan facility of a large service hospital against outsourcing possibilities. Cost per unit scan was calculated by operating costing method and break-even volume was calculated. Then life-cycle cost analysis was performed to enable total cost visibility of the MRI scan in both “In-house” and “outsourcing of facility” configuration. Finally, cost-effectiveness analysis was performed to identify the more acceptable decision option.

Result

Total cost for performing unit MRI scan was found to be Rs 3,875 for scans without contrast and Rs 4,129 with contrast. On life-cycle cost analysis, net present value (NPV) of the “In-house” configuration was found to be Rs-(4,09,06,265) while that of “outsourcing of facility” configuration was Rs-(5,70,23,315). Subsequently, cost-effectiveness analysis across eight Figures of Merit showed the “In-house” facility to be the more acceptable option for the system.

Conclusion

Every decision for acquiring high-end technology must be subjected to life-cycle cost analysis.Key Words: Technology assessment, Cost benefit analysis, Cost-effectiveness analysis     

Cost-effectiveness analysis for technology acquisition

Background: In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.