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Flow cytometry using paraffin-embedded tissue: five years on.

The use of paraffin-embedded tissue for flow cytometry is reviewed. A number of technical modifications of the original 1983 method have been described, aimed at improving the accuracy of DNA measurements by minimizing cell debris or reducing coefficients of variation, and at simplifying sample preparation. Over 100 clinical studies have now been reported, mainly assessing the effect of DNA index on prognosis, and those published up until mid-1988 are summarized in an appendix. More recently there have been developments in the use of monoclonal antibodies to measure oncogene products or proliferation markers in addition to DNA content. Detailed clinical evaluation and standardization of these more sophisticated methods is still some way ahead, but as was the case with DNA index, the use of archival material from patients whose outcome is already known should speed this process.

Animals↗

The characteristics of young and adult dyslexics readers on reading and reading related cognitive tasks as compared to normal readers.

Most of the research into dyslexia has been carried out among children and has raised the question whether the characteristics of young dyslexics are similar to those of adult dyslexics. The aim of this research was, therefore, to confirm whether the cognitive deficits, which appear among young dyslexics on reading and reading related tasks, are similar among adult dyslexics. Four groups of subjects were tested in this study: two groups of fourth graders, dyslexic and normal readers, and two groups of students, compensated dyslexics and normal readers. A comparison of the differences in research measures between the young dyslexics and their control group, and between the adult dyslexics and their control group, clearly indicates that the difference between regular readers and dyslexics is significantly smaller in the adult group on orthographic tasks, and this difference increases in adults on phonological tasks. The findings of this study reinforce the assumption that dyslexics have particular difficulty with the phonological-auditory channel. Another main finding is the slow speed of processing in verbal and non-verbal tasks. It can be assumed that these problems start at a young age and persist in compensated adult dyslexics.

Adult↗

Pulmonary function testing prior to extubation in infants with respiratory distress syndrome.

Pulmonary function testing was performed just prior to extubation on 50 infants mechanically ventilated for treatment of respiratory distress syndrome. All infants were ready for extubation as defined by clinical criteria. Pulmonary mechanics and energetics were measured by a computerized technique that consists of a pneumotachometer to measure flow rates and an esophageal balloon and differential transducer to estimate transpulmonary pressure. Tidal volume, minute ventilation, dynamic lung compliance, pulmonary resistance, and resistive work of breathing were then calculated by high speed microcomputer processing. Successful extubation was defined as greater than 72 hours without respiratory decompensation requiring reinstitution of ventilatory support. Thirty-six (72%) infants were successfully extubated and 14 (28%) infants failed extubation. Infants in the success and failure groups were matched for birth weight, gestational age, age at study, weight at study, weight at study relative to birth weight, use of nasal continuous positive airway pressure (CPAP), and methylxanthines. No statistically significant differences in pulmonary mechanics were seen between the two groups. Data suggests that successful withdrawal of mechanical ventilation may be related to multiple factors such as central inspiratory drive, diaphragmatic endurance, and chest wall stability, in addition to improved lung mechanics. Pulmonary function testing criteria alone may not be useful in determining optimal timing of extubation in premature infants.

Humans↗

Role of extracellular matrix in wound repair by cultured gastric mucosal cells.

Effects of extracellular matrix on wound repair of cultured gastric epithelial cells were assessed. Artificial wounds were made by mechanical cell denudation in confluent rabbit gastric epithelial cell sheets which were formed on different types of extracellular matrix (e.g., collagen type I and type IV, laminin, fibronectin and Matrigel). Changes in wound size were analyzed quantitatively. Cell migration and proliferation were observed in stages of the wound repair process. The speed of wound repair was different with each extracellular matrix studied and was fastest on Matrigel. The type of extracellular matrix used in this study modulated both cell migration and proliferation. Therefore, it is concluded that extracellular matrix plays an important role in rates of gastric mucosal wound healing.

Animals↗

Frontal lobe functions in attention deficit disorder with and without hyperactivity: a review and research report.

We review 22 neuropsychological studies of frontal lobe functions in children with attention deficit disorder with and without hyperactivity (ADD/+H, ADD/-H). Some measures presumed to assess frontal lobe dysfunctions were not reliably sensitive to the deficits occurring in either form of ADD. Tests of response inhibition more reliably distinguished ADD/+H from normal children. Where impairments were found on other tests between ADD and normal subjects, they were highly inconsistent across studies and seemed strongly related to age of the subjects and possibly to the version of the test employed. Other methodological differences across studies further contributed to the discrepant (LD) and conduct problems, with ADD may be an additional confounding factor in some, though not all, of these studies. In a separate reports. The co-morbidity of other disorders, such as learning disabilities (LD) and conduct problems, with ADD may be an additional confounding factor in some, though not all, of these studies. In a separate study, children with ADD/+H (n = 12) were then compared on frontal lobe tests to three other groups: ADD/-H (n = 12), LD but no ADD (n = 11), and normal children (n = 12) statistically covarying for differences in conduct problems across groups. Most measures did not distinguish among these groups. Both ADD groups made more omission errors on a Continuous Performance Test (CPT) than the normal group. All three clinical groups performed more poorly on the word and interference portions of the Stroop Test. Thus, while both types of ADD share some apparent similarities in deficits on a few frontal lobe tests in this study, the totality of existing findings suggests an additional problem with perceptual-motor speed and processing in the ADD/-H group.

Attention↗

Variability and stability in cognitive abilities are largely genetic later in life.

The powerful quantitative genetic design of identical and fraternal twins reared apart (112 pairs) and matched twins reared together (111 pairs) was employed to assess the extent of genetic influence on individual differences in cognitive abilities during the last half of the life span. General cognitive ability yielded a heritability estimate of about .80 in two assessments 3 years apart as part of the Swedish Adoption/Twin Study of Aging. This is one of the highest heritabilities reported for a behavioral trait. Across the two ages, average heritabilities are about .60 for verbal tests, .50 for spatial and speed-of-processing tests, and .40 for memory tests. For general cognitive ability, the phenotypic stability across the 3 years is .92 and stable genetic factors account for nearly 90% this stability. These findings suggest that general cognitive ability is a reasonable target for research that aims to identify specific genes for complex traits.

Aging↗

Brain electrical correlates of psychological measures: strategies and problems.

We explore relationships between brain electrical activity and cognitive performance where qEEG data are correlated with psychological variables gathered at a different time. For a population of 202 healthy adults using univariate and multivariate correlation techniques in a split half replication design, we confirm prior findings that subjects with better psychological scores show shorter evoked potential (EP) latency, suggesting that speed of processing is an important factor in cognitive performance. By canonical correlation we demonstrate a consistent, replicable relationship between electrophysiological and behavioral data. We suggest that reliance upon univariate correlation may have fueled early controversies about relationships between electrophysiology and IQ. In addition we correlate psychological factors with the entire qEEG data set (both EP and spectral analyzed EEG) and demonstrate the use a multidimensional image graphics techniques to assist in visual assessment of the resulting correlation matrices.

Adult↗

An attempt towards differentiating attentional deficits in traumatic brain injury.

Attentional deficits in patients suffering traumatic brain injury (TBI) can occur with minor to severe impact to the brain. Based on reviews of both the cognitive and neurobehavioral literature, the following three concepts of attention are addressed: (a) arousal/alertness, (b) selective attention, and (c) energetic aspects of attention, which include such components as effort, resource allocation, and speed of processing. Within each concept, definitions are proposed, the underlying brain mechanisms are identified, and the specific deficits associated with TBI are explored. This review combines theoretical perspectives and clinical findings with the objective of leading toward a diagnostic differentiation that in turn will benefit treatment planning.

Arousal↗

Experimental identification of technical and database factors that can affect the success of clinical computer systems.

The entry of clinical data into computer systems is an extremely demanding form of transaction processing. High speed is important, especially if the collection involves real-time data. Clinicians must feel that they intuitively understand a system and that it is responsive. Medical data must be easily accommodated without sacrificing accuracy or completeness. Most systems cannot do this. Clinical systems that involve on-line storage of data from patients should employ data-base technology. Systems that lack any of the following capabilities will not succeed: manual data entry, a data dictionary, a file system, utility functions, ad hoc query, and a statistical report generator. These general capabilities must satisfy a number of specific functional requirements if the entire system is to be a success. A group of such requirements have been experimentally validated. These will be discussed and a more comprehensive list presented.

Computer Systems↗

[Kinetoses].

Motion sickness is a well known nausea and vomiting syndrome whose physical signs occur during travel by sea, automobile, airplane, and space. This review describes current concepts concerning the aetiology, nature and therapy of this common phenomenon. Motion sickness involve a neural mismatch or confusion between the vestibular, visual, and proprioceptive systems. Therapy is directed towards decreasing conflicting sensory input, controlling nausea, and speeding the process of adaptation.

Humans↗

MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood.

Nephroblastomatosis is a paediatric renal disease that may undergo malignant transformation. When neoadjuvant chemotherapy is indicated for nephroblastomatosis or bilateral Wilms' tumours, exact volumetric analysis using high-speed data processing and visualization may aid in determining tumour response. Using 3D-volume-rendering software, the 0.5-T MRI data of a 2-year-old girl with bilateral nephroblastomatosis was analysed. Exact volume determination of foci of nephroblastomatosis was performed by automatic and manual segmentation, and the relation to normal renal parenchyma was determined over a 12-month period. At the first visit, 80% (460/547 ml) of the extremely enlarged right kidney was due to nephroblastomatosis. Total tumour volume within the right kidney decreased to 74 ml under chemotherapy. Volume analysis of the two emerging right-sided masses after treatment correctly suggested Wilms' tumour. Three-dimensional rendering of the growing masses aided the surgeon in nephron-sparing surgery during tumour resection.

Child, Preschool↗

Dyslexia: the possible benefit of multimodal integration of fMRI- and EEG-data.

Biological research about dyslexia has been conducted using various neuroimaging methods like functional Magnetic Resonance Imaging (fMRI) or Electroencephalography (EEG). Since language functions are characterized by both distributed network activities and speed of processing within milliseconds, high temporal as well as high spatial resolution of activation profiles are of interest: "where" can dyslexia specific activations be detected and "when" do language processes start to diverge between dyslexics and controls? Due to the network character of language processing, fMRI-constrained distributed source models based on EEG-data were computed for multimodal data integration. First single-case results show that this method could be a promising approach for the understanding of a repeatedly described experimental finding for dyslexia like that of an overactivation in inferior frontal language areas. Multimodal data analysis for the subjects presented here could probably demonstrate that inferior frontal overactivations are the consequence of a phonological deficit and could represent ongoing articulation processes used to solve phonologically challenging tasks.

Adolescent↗

The impact of neuropsychological deficits on functional stroke outcomes.

This review examines the available literature on neuropsychological outcomes of stroke and the literature on the ability of specific areas of neuropsychological deficit to predict functional stroke outcome. The literature reviewed indicates that post-stroke deficits in executive function, memory, language, and speed of processing are common, with those identified as having progressive 'post-stroke dementia' presenting with a similar, though more impaired profile, with increased impairments particularly noted in the area of memory. It is clear that some aspects of neuropsychological functioning (e.g., presence of neglect, aphasia, anosognosia; and verbal memory and attention deficits) show promise as a means of predicting post-stroke functional outcomes. Examining the available literature, it becomes evident that there is a need for long-term, large scale (i.e., population based) follow-up studies, evaluating likely long-term neuropsychological outcomes of stroke and their prognostic utility.

Brain Damage, Chronic↗

A bacteriophage lambda DNA purification procedure suitable for the analysis of DNA from either large or multiple small lysates.

A method for the efficient preparation of high quality bacteriophage lambda DNA from cleared lysates is described. Advantages of the method include high DNA yields (typically around 0.8 micrograms of DNA/1 ml of cleared lysate), speed of processing (approximately 2 h from lysate to DNA), economy, and the absence of any requirement for phenol or chloroform extractions. The technique involves the concentration of phage particles by standard polyethylene glycol precipitation followed by enzymatic treatment to remove contaminating RNA and DNA. Phage particles are then lysed with sodium dodecyl sulfate (SDS) at elevated pH and temperature. Contaminating protein/SDS complexes are rendered insoluble by the addition of potassium acetate and removed by centrifugation. The quality of the resultant DNA is comparable to that prepared by cesium chloride banding for all standard molecular biological purposes providing that spermidine is included in all restriction endonucleases digestions.

Acetates↗

Event-related potentials in patients with Huntington's disease and relatives at risk in relation to detailed psychometry.

Event-related potentials (ERPs) were studied in patients with Huntington's disease (HD) and their offspring at risk in a simple auditory oddball paradigm requiring the counting of the rarer of two stimulus categories. Group statistical analysis revealed prolongation of latencies of components P2, N2 and especially P3 in HD patients and to a lesser extent in at-risks. In a large population of normals the age-latency relationship for component P3 showed a non-linear shape with increasing slope and scatter in the older age groups. A bipartate linear regression analysis splitting the normal population at age 50 was used for detection of abnormalities of P3 latency in individual cases. Abnormal P3 latencies were present in the majority of HD patients and also in 25% of clinically normal at-risks. Correlation analysis of ERP components with detailed psychometry revealed a particularly high association of P3 latencies with measurements requiring speeded information processing in non-verbal tasks. P3 amplitude did not covary with performance scores but unlike P3 latency showed association with depression and psychosis scores. From the results it appears that analysis of ERPs is a useful electrophysiological tool for an objective assessment of cognition both in clinically definite and subclinical stages.

Adolescent↗

Evidence for global developmental change is intact.

In this article, I argue that most of the claims made by Morrison, Morrison, and Keating (1992) do not undermine the key results of the Kail (1988) study and that, contrary to their claims, the evidence still provides support for the original conclusion that a global mechanism is implicated in age-related change in speed of processing.

Adolescent↗

What happens after a hyperactive child commits an error?

Children with a diagnosis of attention deficit disorder with hyperactivity can correct errors, just as controls can. They differ from controls in how they adjust the speed of processing on a trial after they have committed an error. Controls are fast in responding after an error when cognitive load is small. When cognitive load is high, however, they take considerable time to ensure, after an error has occurred, that a correct response is given. After an error has been committed, hyperactive children, irrespective of the demands of load, have no response adjustment and maintain a constant rate of processing.

Attention Deficit Disorder with Hyperactivity↗

Intrinsic neuronal determinants of regeneration.

Axon growth and axon regeneration are co-operative processes; the speed and extent of axon growth are influenced both by the properties of the environment surrounding the axon growth cone, and the properties of the neuron itself. In recent years, the environmental influences on axon growth have received most of the attention directed towards this area of research, but the properties of the neurons themselves are likely to be just as important. Within both adults and embryos there are differences in the growth potential of different neuronal types, and there is also evidence for an overall decrease in the vigour of axon growth with neuronal age.

Animals↗