Assessing the reliability of patient, nurse, and family caregiver symptom ratings in hospitalized advanced cancer patients.

PURPOSE: The purpose of this study was to examine the reliability of symptom assessments in advanced cancer patients under various conditions, including multiple raters (patients, nurses, and family caregivers), occasions, and symptoms. PATIENTS AND METHODS: The study sample consisted of 32 advanced cancer patients admitted to a tertiary palliative care unit. Symptom assessments were completed for each patient on two separate occasions, approximately 24 hours apart. On each occasion, the patient, the primary care nurse, and a primary family caregiver independently completed an assessment using the Edmonton Symptom Assessment System (ESAS). The ESAS is a nine-item visual analogue scale for assessing symptoms in palliative patients. The reliability of the assessments (r) was examined using generalizability theory. RESULTS: Three important findings emerged from this analysis. First, the analysis of individual symptom ratings provided a more meaningful representation of the symptom experience than total symptom distress ratings. Secondly, patients, nurses, and caregivers varied in their ratings across different patients, as well as in their ratings of shortness of breath, which may have been a result of individual rater variability. Finally, reliability estimates (r), based on a single rater and one occasion, were less than.70 for all symptoms, except appetite. These estimates improved substantially (r >/=.70) for all symptoms except anxiety and shortness of breath, using three raters on a single occasion or two raters across two occasions. CONCLUSION: The findings from this study reinforce the need for the development of an integrated symptom assessment approach that combines patient and proxy assessments. Further research is needed to explore individual differences among raters.

Computer-assisted mapping of immunoreactive mammalian gonadotropin-releasing hormone in adult human basal forebrain and amygdala.

Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.

Distribution and organization of cholinergic neurons in the rat forebrain demonstrated by computer-aided data acquisition and three-dimensional reconstruction.

An understanding of the organization of cholinergic neurons in the central nervous system has been an important objective for many years. By developing and applying a new electronic method for mapping tissue sections, we have generated original graphic and quantitative findings on forebrain cholinergic neurons that provide new insight into their distribution and organization. Satoh, Armstrong, and Fibiger (Brain Res. Bull. 11:693-720, 1983) have proposed that in the basal forebrain cholinergic neurons with long axons form a continuum rather than being arranged as a series of discrete nuclear groups. It has been difficult, however, by conventional methods of data analysis and display, to test this hypothesis. By using a digital microscopy system, the position of every cholinergic neuron was marked with 1-micron resolution in tissue sections taken at 90-microns or 180-microns intervals through the entire distribution of these neurons in the forebrain. The three-dimensional reconstruction of these neurons in context shows them to be distributed as a continuous cell column. The column twists and changes position as it is deformed by adjacent neuronal structures, such that its shape and continuity would not be apparent without reconstruction into a computer graphics model. Complementary analyses of the distribution of cholinergic interneurons in dopamine-rich regions of the forebrain indicated that there are regional differences between striatal and olfactory tubercle neurons. Cellular morphometry analyses show the population of cholinergic neurons in the rat to be surprisingly homogenous in size, but not in shape. Graphic and quantitative analyses indicated that there is a striking relationship between the distributions of projection and interneuronal cell groups. We conclude that the basal forebrain cholinergic neurons form a continuum. The chemoarchitecture of this cell group does not conform to the usual cytoarchitectural divisions. The present results, however, taken together with the findings based on Nissl-stained sections and connectional and biochemical data, suggest that the region of this neurochemically defined continuum should be reexamined for consideration as a single functional entity or nucleus: a cholinergic basal nuclear complex.

Neurons containing calcitonin gene-related peptide in the parabrachial nucleus project to the central nucleus of the amygdala.

The source, distribution, and morphology of axons displaying calcitonin gene-related peptide (CGRP) immunoreactivity in the central amygdaloid nucleus of the adult rat were investigated with immunohistochemical techniques, both alone and in combination with retrograde transport of fluorescent tracers. An extremely dense plexus of CGRP-immunoreactive axons is differentially concentrated within the lateral capsular and lateral central subdivisions of the central nucleus, and much lighter concentrations of labeled fibers are present in the rostral part of the medial subdivision. No immunoreactive neurons were observed in the central nucleus in any of the experimental animals. The immunoreactive axons characteristically form prominent pericellular terminal arborizations surrounding unlabeled neurons. The number of cells receiving this dense input increases at caudal levels of the central nucleus. Retrograde label of central nucleus neurons by dye transport from injections into the pontine parabrachial nucleus and the nucleus of the tractus solitarius combined with CGRP immunohistochemistry established that many neurons in the central nucleus which receive dense pericellular innervation from CGRP-immunoreactive axons are projecting caudally to the parabrachial nucleus or, to a lesser extent, to the nucleus tractus solitarii. Central amygdaloid injections of rhodamine-labeled microspheres or fluorogold followed by immunohistochemical localization of cellular CGRP immunoreactivity revealed that the central amygdaloid CGRP fiber plexus originates bilaterally from the parabrachial nucleus. These multipolar CGRP-containing neurons are preferentially concentrated in the external medial and external lateral subnuclei, in the ventral aspect of the parabrachial nucleus. These results relating central amygdaloid CGRP to ascending and descending brainstem pathways, taken together with the extreme density of the fiber plexus, strongly suggest the relevance of the CGRP input to central nucleus function in cardiovascular and other autonomic regulation.

Use of a digital brain atlas to compare the distribution of NGF- and bFGF-protected cholinergic neurons.

The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.

Computer-aided mapping of specific neuronal populations in the human brain.

Antibody-staining methods and computer-aided microscopic systems have been used to generate high-resolution panoramic maps of specific neuronal populations in the human brain (4,6,11). This report focuses on the problems inherent in attempting high-resolution mapping of large brain sections, and describes how they are solved by computer-aided mapping. Further applications of computers to the study of brain structure are considered.

The ventrolateral medulla as a source of synaptic drive to rhythmically firing neurons in the cardiovascular nucleus tractus solitarius of the rat.

We sought to determine whether the caudal ventrolateral medulla (cVLM), at the level of area postrema, influences the rhythmically beating neurons found within the dorsomedial NTS in rat brainstem slices. Intra- or extracellular recordings of neurons firing rhythmically at around 5 Hz were characterized as either auto-active (i.e. pacemaker; AA) or synaptically driven (SD) by pharmacological interventions. The nature of inputs evoked from the ipsilateral cVLM were orthodromic and the majority were excitatory (latency 3-20 ms). Further, this excitatory influence was found to be tonically active in 25/47 cells studied since inactivating the ipsilateral cVLM by localized cooling reduced the firing rate by 0.5-3.0 Hz (23% on average). Neuronal characterization showed that the most consistent and pronounced effect occurred on SD rather than AA cells. Control experiments that cooled other areas of the slice closer to the recording site proved ineffective. Additional studies showed that most rhythmically firing cells in the NTS received an excitatory synaptic input from the solitary tract (ts; latency 3-30 ms). This input was reduced or blocked by inactivating the cVLM in neurons in which the ts latency of activation was greater than 8 ms in half of the neurons tested. Subsequent pharmacological tests revealed that these neurons were predominantly SD. Identified AA neurons received an input from the ts at a shorter latency, typically less than 8 ms, and this was unperturbed by cooling the cVLM in all cases. Further, there was no obvious difference in the baseline discharge rates between cells in the hemi-slice and those recorded in an intact slice. In a hemi-coronal slice cooling the cVLM also produced a 20% decrease in firing rate in identified SD neurons but no consistent change in AA cells. We conclude that (1) the ipsilateral cVLM contributes principally tonic excitatory drive to rhythmically active neurons in the dorsomedial NTS in vitro and this preferentially effects SD neurons; (2) other excitatory drives other than those from the ipsilateral cVLM impinge upon SD cells, the origin of which are relatively local and likely to be in the NTS; (3) in the slice the projection from the cVLM to the NTS appears to be present but the reciprocal connection is absent.

Quantitation of cellular resolution in situ hybridization histochemistry in brain by image analysis.

A new method for relative quantitation of mRNA levels with single neuron resolution is described. Hybridized tissue sections are emulsion dipped, exposed, and developed. The resulting silver grains are visualized using dark-field microscopy at high magnification. The method relies on computer-based image analysis of sequentially located, high resolution, small fields containing the cell images, each of which is analyzed for mRNA content. Maps of cell distributions are constructed, with cell marks color-coded for relative mRNA levels, yielding previously unavailable information on regional distribution of quantitative cellular expression of specific mRNA in brain.

A multi-level analysis of cultural experience and gender influences on causal attributions to perceived performance in mathematics.

BACKGROUND: Causal attributions to academic performance are among the most important factors that influence the student's subsequent achievement behaviour. AIM: The effects of student's gender and cultural experience (region) on the ratings of previously identified causal attribution factors were investigated. SAMPLE: The participants were 341 high school students from the urban (N = 144) and the rural (N = 197) regions of Kenya. There were 205 male and 136 female students. METHODS: Causal comparative research design was used and data collected using the Causal Attribution Scale (CAS). The Hierarchical linear model (HLM) technique was used to test the hypotheses. RESULTS: There were significant gender and cultural experience variations in the mean ratings of the attribution factors. Instructional Strategy was highly rated for perceived success, and lack of Ability for perceived failure. Effort was of least importance in making attribution to either perceived success or failure. CONCLUSIONS: The findings do not concur with research findings from Western and Asian countries where Effort is considered important in making attributions for either perceived success or failure. The findings, however, agree with research findings from Asian and other non-Caucasian societies where success is attributed to external factors (e.g., task difficulty) and failure to internal factors (e.g., ability). These findings have some implications for cross-cultural research in causal attribution as it relates to academic performance. While certain causal attributions studied in 'Western' and Asian cultures differ in terms of perceived success and failure, the current study indicates that other causal attributions are important and used differently by students from Kenya.

The relevance of body motion cues to both functional and dysfunctional communicative behavior.

This study assessed the extent ot which a speaker's visible, spontaneous body movements can contribute to the speech process. An experiment was conducted where subjects responded to videotaped verbal stimuli in one of three conditions (audiovisual, audiovisual without lip and facial cues, and audio alone) over four signal-to-noise ratios. The results indicated that: (1) visual cues can at times significantly improve comprehension scores, even with lip-facial cues not present; (2) visual cues significantly retard decay of comprehension as noise is increasingly introduced; (3) visual cues assist the comprehension of certain types of verbal segments, regardless of the information content expressed in those types of segments. A model of the bimodal aspect of the speech process is developed which illustrates both the cognitive and message-content dimensions. Possible future applications and research objectives are discussed in terms of normal and dysfunctional communicative behavior.

Development and psychometric testing of the Adaptive Capacity Index, an instrument to measure adaptive capacity in individuals with advanced cancer.

BACKGROUND: We have proposed that declines in adaptive capacity, defined as the ability to adapt to multiple stressors, may serve as an indicator of risk for fatigue. A comprehensive measure of adaptive capacity does not exist. OBJECTIVES: In this paper we describe construction of an instrument to measure adaptive capacity, the Adaptive Capacity Index (ACI). DESIGN: Descriptive and psychometric. SETTING: Six sites providing palliative care in Western Canada. INCLUSION CRITERIA: ≥18 years old, diagnosed with advanced cancer, able to read and write English, Mini-Mental Status Exam score ≥22. Pilot study n=48; Main study n=225 stratified using the Edmonton Symptom Assessment Scale (ESAS) tiredness score (≥0 to ≤2 n=60; ≥3 to ≤6 n=108; ≥7 and ≤10 n=57). METHODS: Following ethics approval, 17 experts in symptom management assisted with content validation and consenting individuals completed the Functional Assessment of Cancer Therapy-Fatigue (FACT-F), the Profile of Mood States-Vigor short form (POMS-Vsf), and the ACI. A research assistant collected demographic information and assigned an Eastern Cooperative Oncology Group (ECOG) score. Data were analyzed using descriptive and inferential statistics (i.e., exploratory factor analyses, correlation, multivariate analyses of variance, and multiple regression). RESULTS: Five 6-item ACI factors/subscales (Cognitive Function, Stamina/Muscle Endurance, Sleep Quality, Emotional Reactivity, and Social Interaction) were identified. The ACI-total scale and its subscales were internally consistent (Cronbach's alpha 0.76-0.89), and were significantly correlated with each other, and with each fatigue measure (Pearson's r ranging from -0.724 to 0.634). The ACI total score was sensitive to changes in the ESAS tiredness score. Stamina/Muscle Endurance, Cognitive Function, and Sleep Quality predicted 60.8% of the variance in FACT-F. Stamina/Muscle Endurance and Social Interaction predicted 36.8% of the variance in POMS-Vsf. Stamina/Muscle Endurance and Sleep Quality predicted 8% of the variance in ECOG. CONCLUSIONS: The ACI is reliable and has beginning evidence of validity. In future studies we will examine relationships between ACI subscale scores and subsequent increases in fatigue and explore linkages to physiological processes. We will also establish ACI norms for early and late stage cancers and explore variations in ACI subscale scores base on age or gender.

Computer-aided mapping of brain tissue.

A computer-microscope system is described for use in capturing accurate, quantitative schematic (map) information from anatomical tissue sections. The system provides a rapid and convenient environment for acquisition and analysis of complex structures spread over large 3-D regions of the tissue. As a consequence of the complexity and subtlety of tissue analysis, most of the data acquisition functions of the system involve tight coupling between the hardware and the microscopist to preserve access to human judgment and intelligence. The instrument profoundly affects the ease and accuracy of neurobiological data analysis, making it practical to address previously inaccessible problems. Examples of data analyzed using the system are shown.

Correlates of syntactic abilities in hearing-impaired students.

Total scores on the recently developed Screening Test from the Test of Syntactic Abilities for 382 hearing-impaired subjects between eight and 19 years and in various educational programs were found to be significantly related to hearing threshold level, number of multiple handicaps, age, educational setting, method of communication, and hearing aid usage. Multivariate analysis of variance on the effect of age controlled for hearing loss showed no significant increase in scores after eleven years of age, thus lending support to the thesis that the capacity to acquire language may cease to function at about puberty. The results of stepwise multiple regression analyses showed that, when personal variables were first forced to enter the equation, degree of hearing loss, multiple handicaps, and age accounted for 14%, nine %, an four % of the explained variability, respectively. Over and above these contributions, two manipulable variables--educational setting (a surrogate for integration) and method of communication--added significantly a further 12% and three % to the explained variability in syntactic ability.

The Behavior Of Number-Of-Factors Rules With Simulated Data.

issues related to the decision of the number of factors to retain in factor analysis are identified, and three widely-used decision rules -- the Kaiser-Guttman, scree, and likelihood ratio tests -- are isolated for empirical study. Using two differing structural models and incorporating a number of relevant independent variables (such as number of variables, ratio of number of factors to number of variables, variable communality levels, and factorial complexity), the authors simulated 144 population data sets and, then, from these, 288 sample data sets, each with a precisely known (or incorporated) number of factors. The Kaiser-Guttman and scree rules were applied to the population data in Part I of the study, and all three rules were applied to the sample data sets in Part II. Overall trends and interactive results, in terms of the independent variables examined, are discussed in detail, and methods are presented for assessing the quality of the number-of-factors indicated by a particular rule.

Tonically rhythmic neurons within a cardiorespiratory region of the nucleus tractus solitarii of the rat.

1. Accumulated evidence from the literature led us to investigate whether centrally generated activity was present within a central neuronal network for cardiovascular control. An in vitro approach using a brain stem slice preparation was employed to study the cardiorespiratory region of the nucleus of the solitary tract (NTS) in the rat. 2. We have discovered rhythmically active neurons within a restricted part of the cardiorespiratory NTS. These neurons were localized to regions directly medial and dorsomedial to the solitary tract (ts) at levels 0.2 mm rostral to obex extending caudally to the rostral part of the commissural subnucleus, an area considered to be concerned with cardiovascular regulation. Although other subnuclei were explored for neurons with ongoing activity (i.e., dorsolateral, dorsal, and interstitial) at levels 1.5 mm caudal to 0.75 mm rostral to obex, we failed to find similarly tonically active cells. 3. Intra- or extracellular recordings were made from 85 neurons with a mean firing rate of 5.1 +/- 0.3 (SE) Hz (range 1-15). The majority of these (n = 75) received an excitatory synaptic input from the ipsilateral ts, with latencies ranging between 4 and 20 ms. 4. To determine whether the tonically rhythmic cells were dependent on synaptic excitatory drives or were inherent to the cell, we tested, in 45 neurons recorded extracellularly, the effect of blocking synaptic inputs mediated by excitatory amino acids by applying either DL-2-amino-5-phosphonovaleric acid [APV; N-methyl-D-aspartate (NMDA) antagonist] or MK-801 (NMDA antagonist) with kynurenic acid (Kyn; NMDA, quisqualate, and kainate receptor blocker) to the bath. After bath application of APV and Kyn or MK-801 and Kyn, two different responses were observed. In 19 cells ongoing rhythmic activity was unperturbed, but firing was completely silenced in 26 neurons. In all cases neurons failed to respond to glutamate delivered locally, and the synaptic input evoked from the ts was blocked. This evidence indicates the existence of two cell types: autoactive (AA) or pacemaker-like neurons, the discharge pattern of which depends on intrinsic properties, and synaptically driven (SD) neurons, the activity of which is driven by synaptic inputs. 5. Cobalt chloride (Co) was used to block synaptic effects and was found to increase the discharge rate of AA neurons by 9.9 Hz on average (i.e., cells resistant to APV and Kyn or MK-801 and Kyn). However, the rhythmic activity of cells previously silenced with excitatory amino acid antagonists (i.e., SD cells) was also abolished in the presence of Co.(ABSTRACT TRUNCATED AT 400 WORDS)