Experiential Learning Through a Dementia Simulation.

Health care providers do not always possess the knowledge and skills necessary to optimally manage behavioral symptoms in patients with Alzheimer's disease (AD). The purpose of the current project was to evaluate the use of a simulated virtual reality AD experience on nursing staff sensitivity, awareness, and perceptions of caring for patients with AD. A quasi-experimental design was used. The Long Tour Survey and Approaches to Dementia Questionnaire were administered pre and post simulation and the Perceptions of Caring surveys were administered 3 to 6 weeks post-intervention. Total scores, although not statistically significant, revealed a slight change in the total score and hope subscale, representing more optimism toward people with dementia. The virtual reality AD simulation was a beneficial experience but unable to demonstrate a real change for the majority of participants. [Journal of Gerontological Nursing, 47(11), 39-47.].

Full neurologic recovery and return of spontaneous circulation following prolonged cardiac arrest facilitated by percutaneous left ventricular assist device.

Sudden cardiac arrest is associated with high early mortality, which is largely related to postcardiac arrest syndrome characterized by an acute but often transient decrease in left ventricular (LV) function. The stunned LV provides poor cardiac output, which compounds the initial global insult from hypoperfusion. If employed early, an LV assist device (LVAD) may improve survival and neurologic outcome; however, traditional methods of augmenting LV function have significant drawbacks, limiting their usefulness in the periarrest period. Full cardiac support with cardiopulmonary bypass is not always readily available but is increasingly being studied as a tool to intensify resuscitation. There have been no controlled trials studying the early use of percutaneous LVADs (pLVADs) in pericardiac arrest patients or intra-arrest as a bridge to return of spontaneous circulation. This article presents a case study and discussion of a patient who arrested while undergoing an elective coronary angioplasty and suffered prolonged cardiopulmonary resuscitation. During resuscitation, treatment included placement of a pLVAD and initiation of therapeutic hypothermia. The patient made a rapid and full recovery.

Does the sequence of instruction matter during simulation?

INTRODUCTION: Instructional strategies must be balanced when subjecting students to full-immersion simulation so as not to discourage learning and increase cognitive overload. The purpose of this study was to determine if participating in a simulation exercise before lecture yielded better performance outcomes among novice learners. METHODS: Twenty-nine participants were divided into 2 groups as follows: group 1 participated in simulation exercises followed by a didactic lecture and group 2 participated in the same learning activities presented in the opposite order. Participants were administered a multiple-choice cognitive assessment upon completion of a workshop. RESULTS: Learners who participated in the simulated exercises followed by the didactic lecture performed better on postassessments as compared with those who participated in the simulation after the lecture. A repeated-measures or nested analysis of variance generated statistically significant results in terms of model fit F (α=0.05; 4.54)=176.07 with a P<0.0001. Despite their higher levels of increased performance, 76% of those who participated in simulation activities first indicated that they would have preferred to participate in a lecture first. CONCLUSIONS: The findings of this study suggest that differences occur among learners when the sequencing of instructional components is altered. Learners who participated in simulation before lecture demonstrated increased knowledge compared with learners who participated in simulation after a lecture.

A new insight into the cellular regulation of aqueous outflow: how trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm's canal endothelial cells.

AIM: To test the hypothesis that trabecular meshwork endothelial cells (TMEs) increase the permeability of Schlemm's canal endothelial cells (SCEs) by actively releasing ligands that modulate the barrier properties of SCEs. METHODS: The TMEs were first irradiated with a laser light and allowed to condition the medium, which is then added to SCEs. The treatment response is determined by both measuring SCE permeability (flow meters) and the differential expression of genes (Affymetrix chips and quantitative polymerase chain reaction (PCR)). The cytokines secreted by the treated cells were identified using ELISA and the ability of these cytokines to increase permeability is tested directly after their addition to SCEs in perfusion experiments. RESULTS: SCEs exposed to medium conditioned by the light activated TMEs (TME-cm) respond by undergoing a differential expression (DE) of 1,120 genes relative to controls. This response is intense relative to a DE of only 12 genes in lasered SCEs. The TME-cm treatment of SCEs increased the SCE permeability fourfold. The role of cytokines in these responses is supported by two findings: adding specific cytokines established to be secreted by lasered TMEs to SCEs increases permeability; and inactivating the TME-cm by boiling or diluting, abrogates these conditioned media permeability effects. CONCLUSION: These experiments show that TMEs can regulate SCE permeability and that it is likely that TMEs have a major role in the regulation of aqueous outflow. This novel TME driven cellular mechanism has important implications for the pathogenesis of glaucoma and the mechanism of action of laser trabeculoplasty. Ligands identified as regulating SCE permeability have potential use for glaucoma therapy.

Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: a phase II trial.

BACKGROUND: Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. RESULTS: Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.

Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel and weekly gemcitabine: a phase II trial.

BACKGROUND: Docetaxel and gemcitabine are active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in NSCLC patients failing one prior regimen. PATIENTS AND METHODS: Forty patients were enrolled. Prior chemotherapy was a platinum-based combination in 36 patients, using vinorelbine in 26 patients and etoposide in 10 patients. The other four patients had prior single agents. Tumors were refractory or resistant to front-line therapy in 80% of patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/m2 day 1, with cycles repeated every four weeks. RESULTS: Thirteen patients responded (32.5%; 95% confidence interval (CI): 19%-49%), including one complete and 12 partial responses. Responses were observed at all metastatic sites, with similar response frequencies in platinum-sensitive and platinum-resistant/refractory tumors. The median time to progression for responders was nine months, with two responses lasting longer than a year. Median survival was 8.1 months. Hematologic toxicities included grade 4 neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade 3-4 thrombocytopenia in 9 patients, and anemia requiring red cell transfusions in 9 patients. With the exception of asthenia, severe non-hematologic toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, is an active and safe second-line therapy for NSCLC patients.

Glucocorticoids regulate transendothelial fluid flow resistance and formation of intercellular junctions.

The regulation of transendothelial fluid flow by glucocorticoids was studied in vitro with use of human endothelial cells cultured from Schlemm's canal (SCE) and the trabecular meshwork (TM) in conjunction with computer-linked flowmeters. After 2-7 wk of 500 nM dexamethasone (Dex) treatment, the following physiological, morphometric, and biochemical alterations were observed: a 3- to 5-fold increase in fluid flow resistance, a 2-fold increase in the representation of tight junctions, a 10- to 30-fold reduction in the mean area occupied by interendothelial "gaps" or preferential flow channels, and a 3- to 5-fold increase in the expression of the junction-associated protein ZO-1. The more resistive SCE cells expressed two isoforms of ZO-1; TM cells expressed only one. To investigate the role of ZO-1 in the aforementioned Dex effects, its expression was inhibited using antisense phosphorothioate oligonucleotides, and the response was compared with that observed with the use of sense and nonsense phosphorothioate oligonucleotides. Inhibition of ZO-1 expression abolished the Dex-induced increase in resistance and the accompanying alterations in cell junctions and gaps. These results support the hypothesis that intercellular junctions are necessary for the development and maintenance of transendothelial flow resistance in cultured SCE and TM cells and are likely involved in the mechanism of increased resistance associated with glucocorticoid exposure.

Effect of beta-adrenergic agonists on paracellular width and fluid flow across outflow pathway cells.

PURPOSE: To determine whether the adrenergic agonists epinephrine and isoproterenol regulate fluid flow across endothelial cells cultured from the human aqueous outflow pathway and to evaluate associated cellular mechanisms. METHODS: Confluent monolayers of human trabecular meshwork (TM) or Schlemm's canal endothelial (SCE) cells were grown on porous filter supports. The monolayers were perfused with media while fluid flow, expressed as hydraulic conductivity (HC = microl/min/mm Hg/cm2), was continuously measured in preparations treated with isoproterenol, epinephrine, or control medium. Morphometric ultrastructural methods were used to measure the area occupied by the intercellular space and by each cell. RESULTS: SCE cells and TM cells exposed to isoproterenol or epinephrine responded with an increase in transendothelial fluid flow. Dose-response curves for both adrenergic agonists showed that HC increased linearly as a function of the log of the isoproterenol and epinephrine concentration. At 10(-4) M isoproterenol, the HC increased threefold, and threshold conditions were reached at 10(-9) M. The increase in HC was apparent after isoproterenol had been applied for 1 hour, reached a peak in 3 to 4 hours, and declined gradually to return to baseline conditions in 10 to 12 hours. Morphometric analyses showed that the area occupied by the intercellular space increased fourfold when isoproterenol was used at 10(-4) M, whereas the cell area decreased as a function of the concentration of adrenergic agonist. Epinephrine's effects on HC and cell morphology were blocked by pretreatment with equimolar concentrations of the nonselective beta-blocker, timolol. CONCLUSIONS: Epinephrine and isoproterenol increase flow through the paracellular pathway of SCE and TM cells through a beta-receptor mediated response that widens the intercellular space and reduces cell area. These findings support the hypothesis that epinephrine decreases the intraocular pressure in glaucoma therapy by promoting fluid flow across the SCE and TM cells lining tissues of the major aqueous outflow pathway.

Parent information binder: individualizing education for parents of preterm infants.

To assist the parents of preterm infants at Mount Sinai Hospital, Toronto, Canada, we have developed a unique and creative method of individualizing parent information: The parent information binder (PIB). This method has supported a shift from nurse-directed education to parents as partners in their own education. Parents and health care professionals utilize the PIB collaboratively to facilitate organization and collection of information, which is individualized according to the infant's level of wellness and the parents' readiness to receive the information. This approach empowers parents to be active and integral participants in decisions regarding their infants' hospital care.

Storage, metabolism, and processing of 125I-fibroblast growth factor-2 after intracerebral injection.

Basic fibroblast growth factor (FGF-2) is a potent trophic agent for both neuronal and non-neuronal cells of the mammalian CNS. It can enhance survival and neurite outgrowth of a variety of neuronal types in vitro and in vivo, and recently has been shown to stimulate neuroblast proliferation in culture. To determine the most effective means of introducing FGF-2 into the brain, and to further our understanding of the behavior of exogenous FGF-2 following intracerebral injection, we examined the diffusion and degradation of 125I-FGF-2 following intraventricular or intraparenchymal injection. SDS-PAGE and autoradiography show that when radiolabelled FGF-2 is injected into the parenchyma of the rat brain, it remains at the site of injection where it is detectable for several days. During this time, it is slowly metabolized to 2 specific heparin-binding metabolic fragments that are virtually identical to the ones described for its metabolism by neurons and astrocytes in vitro. Microscopic examination and autoradiography of these tissue sections show that within these areas, FGF-2 diffuses throughout the site of injection. Initially, it migrates along adjacent fiber tracts, binds to specific cells and to basement membranes of the microvasculature, but later on it remains associated to basement membranes and non-neuronal cells. Based on its slow clearance and slow rate metabolic degradation, this FGF-2 is presumed to be in a sequestered form and to have limited activity. In contrast, the intraventricular injection of 125I-FGF leads to a rapid clearance, with some binding to ependymal cells lining the ventricles and little translocation into the parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Orienting behavior in hamsters with lesions of superior colliculus, pretectum, and visual cortex.

We examined cortical and subcortical mediation of visual locomotor orienting function by comparing the behavior of hamsters with discrete bilateral lesions affecting the pretectum, superior colliculus (SC), or visual cortex (VC). Orienting and approach to stationary targets was evaluated by measuring the accuracy of hamsters' approaches to small black apertures, located at eye level along the wall of a circular white arena. Hamsters with bilateral ablation of the visual cortex were slightly impaired for approaches to central field targets, whereas those with ibotenic acid lesions of the pretectum (which spares fibers of passage and thus leaves tectal afferents intact) were totally unimpaired. Hamsters with transection of the brachium of SC (BSC) at the prectectal-SC (PT-SC) border were severely impaired in their ability to approach stationary targets in central and peripheral fields. Thus, we did not detect any of the central field sparing that has been reported by others for rodents with similar lesions. Several possible reasons for the disparity between our results and those of others are discussed. Overall, our results indicate that in hamsters the SC is essential for normal visually guided approach to dark, stationary targets throughout the visual field. Further, our results and qualitative observations indicate that the approach errors are most likely due to deficits of visuomotor integration rather than to a lack of visual scanning.

Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus.

Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the "wrong" (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions.

Partial lesion of the substantia nigra: relation between extent of lesion and rotational behavior.

Recent work, largely carried out in primate models of Parkinson's disease (PD), indicates that residual dopaminergic neurons in the midbrain and their axons to the nucleus accumbens and striatum can be stimulated to sprout collateral axons, reinnervate the striatum, and cause a behavioral recovery. We sought to create a partial lesion model of PD in the rat that would (i) mimic the pattern of cell loss in human patients in early stages of PD, and (ii) permit examination of experimental manipulations that promote sprouting of axons of the surviving dopaminergic cells in the midbrain. Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNpc) were tested weekly for rotational asymmetry following administration of apomorphine or amphetamine. After completion of behavioral testing, the animals were sacrificed and the brains immunolabeled for tyrosine hydroxylase (TH). Analysis of anatomical and behavioral data revealed a strong correlation between number of remaining TH-immunoreactive cells in the SNpc and the number of rotations induced by apomorphine. There was no significant correlation between number of remaining TH-immunoreactive nigral neurons and number of rotations induced by amphetamine. We also examined the relation between area in the denervated striatum with remaining TH-immunoreactive axons, number of TH-immunoreactive cells in the lesioned SNpc, and rotational behavior. As expected, there was a strong correlation between area innervated by TH-immunoreactive axons and number of remaining TH-immunoreactive neurons in the lesioned SNpc. Total extent of innervation was also correlated with number of apomorphine-induced rotations but not with number of amphetamine-induced rotations.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine effects on major cell types of the aqueous outflow pathway: in vitro studies/clinical implications.

We have investigated the possibility that direct cellular effects may mediate the action of EPI to lower the IOP. To do this, cultured HTM and SCE cells were grown as monolayers over a millipore-filter support structure. The monolayers were exposed to various adrenergic agonists and antagonists while flow of the perfusate (DME + 5% FBS) was measured using a specially-designed computer-linked apparatus. Exposure of the cells to 10(-5) M EPI for around 2 hours led to a rapid twofold increase in HC which gradually declines over the next 12 hours. Continuous exposure of either cell type (ie, HTM or SCE cells) to EPI or ISO resulted in a four- to eightfold increase with a maximal effect measured around 10 hours and a half maximal effect at 2.5 hours. Administration of c-AMP alone gave similar responses. In agreement with clinical studies, timolol blocks EPI's effect completely while betaxolol acted as a partial antagonist. These findings suggest that the cellular changes and the increase in HC are mediated by a beta-2 receptor. There are many similarities between the responses observed using our in vitro system and the IOP-lowering response observed in vivo after the topical application of EPI (eg, concentration, time course, duration, and magnitude). The clinical implications of these preliminary results are discussed and it is proposed that the described in vitro system may be useful to select new adrenergic drugs for glaucoma therapy.

Kinetics of phagocytosis in trabecular meshwork cells. Flow cytometry and morphometry.

Confluent human trabecular meshwork (HTM) cells from three different donors and at various stages of serial passage were fed fluorescein-labeled polystyrene beads. Phagocytosis was monitored for up to 6 days using flow cytometry, fluorescence microscopy, and morphometric calculations from comprehensive electron microscopic observations at key time points. During the first 4 hr after initiation of phagocytosis, the confluent endothelial monolayer lost its cohesiveness and became segregated into separate cells. During the first 3 days the cells underwent marked and progressive changes in shape and size. After 4 days, some cells detached from the dish, as necrotic debris and degenerative changes appeared. The kinetics of phagocytosis in this stable, confluent monolayer showed that recruitment (the percentage of cells which had ingested at least one bead) proceeded semilogarithmically, with 50% of the cells recruited by 8 hr and 97% by 96 hr. The time course of phagocytosis (ie, the average number of beads phagocytosed per cell) is described by a sigmoidlike curve, reaching half-maximum at 40 hr and maximum (about 500 beads per cell) at 96 hr. The rate of uptake (ie, the first derivative of the average number of beads per cell) reached a peak (nine beads per cell per hr) at 24 hr and then decelerated slowly over the next 5 days. Cytochalasin B treatment, as a control, reduced phagocytosis by approximately 70%. Flow cytometry, when combined with electron microscopy, should provide a useful tool to examine phagocytosis in HTM cells exposed to steroids and other hormones and drugs.

Visualizing anterogradely transported HRP by use of TMB histochemistry: comparison of the TMB-SNF and TMB-AHM methods.

Horseradish peroxidase (HRP), a commonly used enzymatic marker for tracing pathways in the central nervous system, can be visualized histochemically with the aid of the chromogen tetramethyl benzidine (TMB). In a recent report, Olucha and collaborators (J Neurosci Meth 13:131, 1985) introduced the use of ammonium heptamolybdate (AHM) as a substitute for sodium nitroferricyanide (SNF) which serves to stabilize the HRP reaction product. This TMB-AHM method of Olucha et al. proves superior to the TMB-SNF method of Mesulam (J Histochem Cytochem 26:106, 1978) in that the reaction does not produce crystalline artifact. For visualization of retrogradely transported HRP, the two methods are reportedly equivalent in sensitivity. In the work reported here, we have compared the sensitivity of the two methods in detecting HRP that was transported anterogradely after intraocular injections of the enzyme in normal adult and neonatal hamsters, as well as in animals with lesions of the superior colliculus or retina. We demonstrate that the TMB-SNF method is decidedly more sensitive than the TMB-AHM technique for visualization of anterogradely transported HRP. This difference in sensitivity is especially evident in regions of sparse projections.