Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats.

The progression of epileptiform activity following soman (GD) exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus, which may lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties, which conceptually may be a beneficial therapeutic approach to the treatment of nerve agent exposure. In the present study, rats were exposed to 1.2 LD50 GD or saline, treated with atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure, and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc) and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD exposure, performance was evaluated using a battery of behavioral tests to assess motor coordination and function, sensorimotor gating, and cognitive function. Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure activity, neuropathological damage, and cognitive deficits compared to diazepam alone, but did not attenuate the GD-induced sensorimotor gating impairment. These findings show that physiological, behavioral, and neuropathological effects of GD exposure can be attenuated by treatment with caramiphen as an adjunct to therapy, even if administration is delayed to 30min after seizure onset.

A nanoparticle-coated chemiresistor array as a microscale gas chromatograph detector for explosive marker compounds: flow rate and temperature effects.

The effects of flow rate and temperature on the performance of a microscale gas chromatographic (µGC) detector consisting of a chemiresistor (CR) array coated with different thiolate-monolayer-protected gold nanoparticles (MPNs) are described with respect to the analysis of three gas-phase markers of the explosive trinitrotoluene (TNT): 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), and 2,3-dimethyl-2,3-dinitrobutane (DMNB). In chamber tests, sensors were stable at 70 °C for several days in air, with <2% sensitivity drift per day and virtually no change in the array response patterns. In tests with a conventional upstream GC column, increasing the array temperature from 55-80 °C (1.2 mL min(-1)) led to similar (i.e., 4-6.6-fold) decreases in sensitivity, increases in the limits of detection (LODs), and increases in (estimated) chromatographic resolution. Increasing the flow rate from 1.1-3.7 mL min(-1) (70 °C) led to ∼1.3-2-fold decreases in sensitivity and LOD for 2,4-DNT and 2,6-DNT, a ∼2-fold net increase in LOD for DMNB (passes through a maximum), and a <2-fold increase in resolution. Results indicate that the rates of desorption of the marker vapors out of the MPN films are important determinants of observed trends. With Si-micromachined focuser/injector and separation column devices placed upstream of a CR array held at 70 °C, a mixture of the two primary markers, 2,4-DNT and DMNB, and four similarly volatile alkane interferents was separated in 1.5 min at 3 mL min(-1).

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: synergism with the benzodiazepine diazepam.

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA(A)) receptors. However, seizure activity itself causes the endocytosis of GABA(A) receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-d-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20mg/kg, im) and DZP (10mg/kg, sc), administered both separately and in combination, at 10, 20 or 30min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD(50); 132µg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20-30min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity.

Effect of chronic MK-801 and/or phenytoin on the acquisition of complex behaviors in rats.

The purpose of the present experiment was to assess the effects of chronic MK-801 (an N-methyl-D-aspartate receptor antagonist) and/or phenytoin (a sodium channel blocker) treatment on behavioral acquisition and performance in rats. Learning, audio/visual discrimination and motivation were modeled using incremental repeated acquisition (IRA), audio/visual discrimination (AVD) and progressive ratio (PR) tasks, respectively. MK-801 and/or phenytoin were administered daily, 7 days/week by orogastric gavage beginning just after weaning on postnatal day (PND) 23 and continuing until PND 306. Monday through Friday behavioral assessments began on PND 27 and continued until PND 430. Throughout treatment, subjects in the high dose MK-801 (1.0 mg/kg/day) and the high dose drug combination (1.0 mg/kg/day MK-801+150 mg/kg/day phenytoin) groups exhibited decreased body weight gains compared to control subjects. For these two affected groups, response rates were also decreased in all tasks. Task acquisition, as evidenced by an increase in response accuracy, was decreased for both these groups in the AVD task, but only for the high dose MK-801 group in the IRA task. The data suggest that chronic MK-801 treatment adversely affects the acquisition of IRA and AVD task performance and that the inclusion of phenytoin in the MK-801 dosing regimen blocks some of the adverse effects of chronic MK-801 treatment on IRA task acquisition. These findings are in marked contrast with those observed in nonhuman primates and suggest important species differences associated with chronic exposure to compounds that block NMDA receptors and/or sodium channels.

Response sequence difficulty in an incremental repeated acquisition (learning) procedure.

Incremental repeated acquisition (IRA) procedures require subjects to learn a different sequence of behavioral responses during each experimental session with required response sequences increasing incrementally in length as subjects demonstrate mastery of shorter response chains. The purpose of this study was to investigate whether some response sequences are more or less difficult to acquire than others. If true, then sequence difficulty must be considered as a potential confound when attempting to assess the effects of drugs and other experimental manipulations on learning. Accuracy for each response sequence was assessed using control data from two large rodent studies, and each sequence was classified as easy, moderate or hard. Sequences that required responses on adjacent levers were easier (characterized by higher accuracies) to acquire than those that required responses on non-adjacent levers. In addition, sequences that required responses on only two of three response levers were easier to acquire than those that required responses on all three levers. These results provide strong evidence for differing levels of response sequence difficulty in IRA procedures with sequence difficulty seeming to be dependent on whether or not responses are required on adjacent levers.

Behavioral effects associated with chronic ketamine or remacemide exposure in rats.

The effects of chronic exposure to ketamine or remacemide on the acquisition and performance of food-reinforced operant behaviors was assessed in female Sprague-Dawley rats. Ketamine is an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, whereas remacemide is an active central nervous system compound with both NMDA receptor antagonist and sodium channel blocking properties. Learning, audio/visual discrimination and motivation were modeled using incremental repeated acquisition (IRA), audio/visual discrimination (AVD) and progressive ratio (PR) tasks, respectively. Ketamine (10 or 100 mg/kg/day), remacemide (100 or 150 mg/kg/day) or water was administered daily (7 days/week) via orogastric gavage beginning on postnatal day (PND) 23 and continuing until PND 257. Monday through Friday behavioral assessments began on PND 27 and continued until PND 383. Chronic treatment with the high dose of ketamine decreased response rate in all tasks suggesting decreased motivation or motoric capabilities. Chronic treatment with ketamine or remacemide had no effect on the acquisition of IRA task performance at any dose tested. While chronic treatment with either high-dose ketamine or low-dose remacemide only delayed the acquisition of AVD task performance for a brief period midway through treatment, chronic treatment with high-dose remacemide delayed the acquisition of AVD task performance until late in treatment. The findings for ketamine are quite different from those of MK-801 (the prototypic NMDA receptor antagonist) in a previous rat study in which MK-801 severely disrupted the acquisition of both IRA and AVD task performances. These observations suggest important differences in the mechanism of action between ketamine and MK-801. For example, ketamine has a much lower binding affinity than MK-801 for the NMDA receptor, the dopamine transporter and the dopamine D2 receptor. In addition, the findings for remacemide observed in rats are in marked contrast with those seen in monkeys where chronic remacemide had profound disruptive effects on the acquisition of both IRA and AVD task performances and suggest important species differences.

Moderating and mediating effects in causal models.

This article explains causal relationships in conceptual models of mental health phenomena. Direct, moderating, mediating, and reciprocal effects among variables are defined, appropriate statistical analyses are described, and the correct interpretations of moderating versus mediating effects are discussed. Examples are provided that will help the reader to distinguish between moderating and mediating effects.

Continuum of care for Alzheimer's disease: a nurse education and counseling program.

This study evaluated a one year long course education and counseling program with 93 family caregivers of elders afflicted with Alzheimer's disease. The elders had received treatment for agitation in an inpatient setting and were subsequently discharged to the caregivers' home. Caregivers were randomly assigned to an experimental group (n = 68) and a control group (n = 25). Baseline assessments (Time 0) were conducted while the elder was an inpatient. Postdischarge interventions and assessments were conducted at 2 weeks, 6 weeks, 12 weeks, and 6 and 12 months (Times 1-5 respectively). There were no significant treatment effects for care recipient agitation, caregiver stress, depression, and physical health, and no significant differences between groups in rates of institutionalization for afflicted elders. Longitudinal data, however, revealed several important trends. Afflicted elders' agitation rose steadily for control group subjects at Times 3 through 5 but declined for experimental group subjects. Caregiver depression increased for control group subjects at Time 5, but declined for experimental group subjects. Caregiver physical health declined for control group subjects at Times 4 and 5 but was maintained for experimental group subjects. A significantly higher number of afflicted elders were still at home among experimental group subjects at the end of the one year study. The difficulties in demonstrating efficacy of interventions with family caregivers of Alzheimer's disease are discussed. Finally, the issue of data collection being perceived as support by control group subjects is evaluated.

The role of a clinical outcome research evaluator. A graduate nursing student's experience.

Outcome evaluation research is a relatively new paradigm that allows those in nursing to explain the impact of an intervention. The term efficacy is used when an intervention is evaluated as part of a controlled research study, while effectiveness denotes outcome evaluation of uncontrolled interventions in diverse settings. This article describes a graduate nursing student's supervised research experience that contributed to evaluating the efficacy of an intervention consisting of counseling caregivers of elders with dementia via telecommunications. The student's preparation for the role of research evaluator included acquisition of conceptual knowledge about evaluation research, interviewing techniques, and analytical skills to interpret evaluation data. Conceptual knowledge focused on the application of the Donabedian Structure. Process, Outcome Model and issues such as stakeholder, vested interest, and confidentiality. Data collection interviews involved the use of open-ended questions (qualitative) and administration of a structured questionnaire (quantitative). Analysis of qualitative data required identification of positive and negative themes; item responses on the structured questionnaire were compiled as percentages. Findings from the evaluation were used to improve the design of an ongoing intervention study.

Emotional and physical health of spouse caregivers of persons with Alzheimer's disease and stroke.

Providing care for a cognitively impaired spouse can adversely affect caregivers' health. It is not known how early in the caregiver's 'career' emotional and physical health deteriorates. The progressive deterioration associated with Alzheimer's disease (AD) may have different effects on caregivers' health when compared with the potential recovery following a stroke. An exploratory study was conducted with 42 couples, equally divided among early phase AD, ischaemic stroke after hospital discharge, and well controls. Couples were evaluated at baseline (time 1), 6 months (time 2) and 1 year (time 3). At time 1, depression was significantly higher in AD and stroke caregivers when compared to controls. Over time, depression increased significantly for AD caregivers with 21% evidencing moderate to severe depression at time 1 and 50% at time 3. For stroke caregivers there was a significant interaction effect with race: white stroke caregivers' depression increased over time while African American stroke caregivers' depression decreased. Physical health was not significantly different for the three groups and remained stable over time. Cognitive and functional impairment levels of care recipients were significantly related to stroke caregivers' but not AD caregivers' depression. Long-term counselling and support to family caregivers is advocated.

Racial differences in health status and health behaviors of older adults.

BACKGROUND: Little is known about racial differences in health status and health behaviors of older adults, especially among the oldest old. OBJECTIVES: To investigate racial differences in health status and health behaviors of African American and Caucasian older adults and to identify factors that influence health behaviors of older adults. METHOD: A descriptive comparative study using data from the Georgia Centenarian Study was conducted. The subjects were 248 older adults (181 Caucasians and 67 African Americans) ranging in age from 60 to 107 years. Demographic characteristics, health status, and four health behaviors were assessed. RESULTS: African Americans had significantly lower mental health (p < .001) and poorer self-perceived health (p < .01) than did their Caucasian counterparts; however, when covaried with education and income, racial differences in self-perceived health were eliminated, and differences in mental health decreased but remained significant (p < .05). Using univariate analyses, only two health behaviors, physical activity and eating breakfast regularly, showed significant racial differences. Relatively few older adults participated in leisure-time physical activity. Logistic regression analyses indicated that race was not significantly related to any health behaviors. Age, gender, and physical health status were most frequently related to health behaviors. CONCLUSION: The findings indicated no robust racial differences in health status and health behaviors, especially when education and income were controlled. More research is recommended to clarify the factors that explain health behaviors of older adults.

Telecommunication interventions for caregivers of elders with dementia.

Caregiver Interventions via Telecommunications (CIT) is designed for family caregivers of elders with dementia. Building on Riegel's dialectical theory of human development, the authors argue that psychotherapeutic interventions, made highly accessible by telecommunication technology, assist caregivers to achieve positive developmental outcomes. Specific components of CIT are described, and an outline for a structured protocol is provided. Advantages, disadvantages, and future directions of telecommunications therapy are discussed.

Human development in the context of aging and chronic illness: the role of attachment in Alzheimer's disease and stroke.

Does chronic illness in older people provide potentials for human development? To date, this question has not been adequately addressed by dynamic theorists of human development. In this article, two illness trajectories, Alzheimer's disease and stroke, are examined to illustrate emerging changes in human development over each course of illness and the increasing importance of attachment behavior among ill elders and their family members. It is argued that the phenomenon of attachment links ailing older people to their environment, and that attachment is vital if human development is to continue.

Alzheimer's disease afflicted spouses who remain at home: can human dialectics explain the findings?

When one spouse has Alzheimer's disease (AD), marital interactions tend to decline. Findings from this study suggest that level of spousal interactions influence longitudinal outcomes for afflicted spouses. Thirty AD spouses and their spouse caregivers were assessed at baseline (time 1) and two years later (time 2). Continued in-home care at time 2 is predicted by high levels of positive spousal interactions, high caregiver commitment, good caregiver health, and shorter time as caregiver (all assessed at time 1). The same variables but in an inverse relationship predict which AD spouses are deceased at time 2. Nursing home placement is predicted by AD spouses' higher educational level, unhappy marital relationships, and low caregiver commitment. Afflicted spouses' cognitive and functional impairment levels, their physical health and depression do not predict outcomes. A theoretical explanation is developed drawing on Riegel's dialectical theory of human development and Bowlby's attachment theory. It is suggested that interactions between spouses are crucial for afflicted spouses' survival.

The impact of Alzheimer's disease on the marital relationship.

Caregiver-Alzheimer's afflicted spouse dyads were compared with healthy married couples. The former dyads were incongruent in their perception of tension and agreement over sexual issues, and caregivers differed significantly from well-group spouses on companionship and total marital quality. Only 27% of the Alzheimer's couples versus 82% of the well couples were still sexually active. High sexual activity occurred in 14% (n = 4) of male afflicted spouses (50% of sexually active couples), and of these, two were age less than or equal to 60. High sexual activity was problematic to three-fourths of the female caregiver spouses. Caregivers evidenced adaptation and control; afflicted spouses tended to deny problems and had distorted perceptions of interactions with their caregiver spouses.

A model to facilitate interactive planning.

The IPEM has helped stakeholders in a very complex tertiary medical center to understand the importance of interactive planning. The need to do so was highlighted by nursing demand and shortage issues. Deliberate efforts to refine and to restructure patient care within a hospital necessitates multidisciplinary planning and problem solving, collaborative nurse/physician relationships, and sound recruitment/retention policies. The experience at one hospital shows how nurse executives can take ownership of issues that help to reduce nursing supply and demand problems. Restructuring of patient care is one method of addressing demand; supply can be addressed locally by collaborative relationships with schools of nursing to increase students' access to education. Enhancing professional nursing practice is the responsibility of nursing service executives as well as educators. Yet, ultimately, it is the hospital's professional environment and reward system that influences nurses' choice of practice setting.

Mental health in older spouses: the dynamic interplay of resources, depression, quality of the marital relationship, and social participation.

This study demonstrates a conceptual linkage between exchange theory and psychoanalytic theory of depression. The effects of diminished resources and the dynamic relationships between depression, quality of the marital relationship, and social participation were investigated with a sample of 229 community residing, married older people (Duke Longitudinal Study) using a combined structural and measurement model with linear structural relations (LISREL) analysis. Findings are that some resources have direct effects on depression, marital quality, and social participation. However, it is through the pathway of depressive moods that ill health, retirement, and stress have their negative effects on the marital relationship. Depressive moods do affect social participation, but psychosomatic symptoms of depression do not affect the amount of social participation nor the marital relationship. Recognizing depressive moods as intervening variables is important because older people tend to deny feeling depressed. Without a conceptual linkage of exchange and depression theories, this pathway would not have been identified.