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Biomedical subjects

G McAnulty

Publications and source records attributed to G McAnulty.

9 recordsLinked to original sources

Nonsteroidal anti-inflammatory drugs in perisurgical pain management. Mechanisms of action and rationale for optimum use.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents with similar actions but diverse chemical structures. Aspirin (acetylsalicylic acid) and sodium salicylate were the first drugs of this type to be used clinically. However, over the past 3 decades there has been a dramatic increase in the number of NSAIDs available for the treatment of postoperative pain. Tissue injury, such as occurs with surgical intervention, is associated with the release of numerous inflammatory mediators including prostaglandins. Prostaglandins derived from the arachidonic acid cascade are implicated in the production of inflammatory pain, and in sensitising nociceptors to the actions of other mediators. They are synthesised from arachidonic acid via the endoperoxide biosynthesis pathway, the initial step of which is catalysed by the enzyme cyclo-oxygenase. Two forms of the cyclo-oxygenase enzyme (COX-1 and COX-2) have been characterised. COX-1 is important in circumstances where prostaglandins have a protective effect such as gastric mucus production and renal blood flow maintenance. NSAIDs inhibit the synthesis of prostaglandins at 1 or more points in the endoperoxide pathway. Three mechanisms of inhibition of the biosynthetic enzymes have been proposed: (i) rapid, reversible competitive inhibition; (ii) irreversible, time-dependent inhibition; and (iii) rapid, reversible noncompetitive (free radical trapping) inhibition. In addition, there is evidence that NSAIDs have a central antinociceptive mechanism of action that augments the peripheral effect. This may involve inhibition of central nervous system prostaglandins or inhibition of excitatory amino acids or bradykinins. There is considerable variability in the pain relief obtained from NSAIDs. Such variability in drug response may be explained in terms of differences between agents with respect to either pharmacodynamic actions or pharmacokinetic parameters or a combination of both. Stereoisomerism, where preparations exist as racemic mixtures and where only 1 enantiomer is active, may also be important. However, chiral inversion from inactive to active enantiomer may occur and may be rapid or slow. NSAIDs have numerous adverse effects. Gastrointestinal disturbances including ulceration are the commonest adverse responses to NSAIDs and carry the greatest risk of death. Also significant are renal impairment and an increased risk of postoperative haemorrhage. Asthma and allergic reactions are uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents, Non-Steroidal

Abnormal flash visual evoked response in melancholia: a replication study.

Grand mean flash visual evoked responses (FVER) were measured in two new groups of depressed patients with melancholia to replicate findings of an abnormal FVER in a previously reported pilot study (Vasile et al 1989). These different, independently collected groups of melancholic patients demonstrated a statistically significant negative deviation of the FVER 224-300 msec poststimulus maximal in the midline centroparietal region when compared with appropriate normative age-matched control groups (n = 56) in each group). We utilized the identical computer-based quantified neurophysiological technique with mapping to analyze the data in all three melancholic patient groups--the pilot group (n = 9) with mean age 73.1 years, an older replication group (n = 14) with mean age 75.5 years, and a younger replication group (n = 15) with mean age 63.8 years. We also studied a group of depressed patients without melancholia (n = 11) with mean age 65.2 years, and found a similar, but less pronounced, alteration of the FVER. Lastly, we studied a group of nondepressed neuropsychiatric patients (n = 10) with mean age 61.9 years and found no abnormality of the FVER. Our data suggest that a gradient of FVER abnormality exists in depressed patients, most prominent, but not limited to elderly melancholic patients.

Aged

Unrestricted principal components analysis of brain electrical activity: issues of data dimensionality, artifact, and utility.

Principal components analysis (PCA) was performed on the 1536 spectral and 2944 evoked potential (EP) variables generated by neurophysiologic paradigms including flash VER, click AER, and eyes open and closed spectral EEG from 202 healthy subjects aged 30 to 80. In each case data dimensionality of 1500 to 3000 was substantially reduced using PCA by magnitudes of 20 to over 200. Just 20 PCA factors accounted for 70% to 85% of the variance. Visual inspection of the topographic distribution of factor loading scores revealed complex loadings across multiple data dimensions (time-space and frequency-space). Forty-two non-artifactual factors were successful in classifying age, gender, and a separate group of 60 demented patients by linear discriminant analysis. Discrimination of age and gender primarily involved EP derived factors, whereas dementia primarily involved EEG derived factors. Thirty-eight artifactual factors were identified which, alone, could not discriminate age but were relatively successful in discriminating gender and dementia. The need to parsimoniously develop real neurophysiologic measures and to objectively exclude artifact are discussed. Unrestricted PCA is suggested as a step in this direction.

Adult

Neurophysiological heterogeneity and the definition of dyslexia: preliminary evidence for plasticity.

Developments in the field of quantified electroencephalography have enhanced visualization of brain function in the learning disabilities. Optimal utilization of these techniques requires that populations under study be unambiguously defined. Evidence from the literature demonstrates that brain electrical activity of children with reading disability is more extensive and differs from that seen in children with "dyslexia-pure". Preliminary data are presented demonstrating that electrophysiological change seen in children with dyslexia-plus (dyslexia and attentional deficit disorder) could not be predicted by knowledge of electrophysiologic change in children with dyslexia-pure alone and attentional deficit disorder alone. Data from our laboratory are summarized to show that within dyslexia-pure the anomic, dysphonemic and global Denckla subtypes differ electrophysiologically from one another. Of particular interest is the demonstration that regions of electrophysiological difference among these subtypes may reflect compensatory mechanisms rather than pathological change. Finally, a case study is presented demonstrating advantageous effects of remediation upon brain electrical function. As both spontaneous and environmentally induced change in brain function can be documented, developmental dyslexia in its broadest terms appears to represent a more dynamic or plastic process than previously appreciated.

Anomia

Lecithin: absence of neurophysiologic effect in Alzheimer's disease by EEG topography.

Ten patients with Alzheimer's disease participated in a 26-week double-blind trial of lecithin. EEG data were recorded at baseline, after administration of the placebo, and after administration of the drug. Topographic maps of EEG spectra were compared when patients were on and off drugs. A direct comparison of drug and nondrug data was not significant. A second approach, comparing differences between drug and nondrug with differences between the two nondrug conditions, also produced no evidence of a drug treatment effect. The data confirm other reports that lecithin has no effect upon spectrally analyzed EEG activity in Alzheimer's disease.

Aged

Individualized behavioral and environmental care for the very low birth weight preterm infant at high risk for bronchopulmonary dysplasia: neonatal intensive care unit and developmental outcome.

We hypothesize that the respiratory and functional states of the very low birth weight infant with bronchopulmonary dysplasia can be improved in the neonatal intensive care unit by prevention of inappropriate sensory input. To test this hypothesis, we developed for preterm newborns a behavior observation method that catalogues specific reaction patterns according to putative stress and relaxation behaviors. We then collected behavioral information and heart rate, respiratory rate, and transcutaneous PO2 readings before, during, and after routine care-giving interventions. Eight control and eight experimental infants were selected for study based on the following criteria: birth weight less than 1,250 g, gestational age less than 28 weeks, on the respirator greater than 24 hours in first 48 hours of life at greater than or equal to 0.60 FiO2 for more than two hours during first 48 hours of life. Additionally, the two groups were comparable on other medical and demographic variables, including severity of respiratory status for the first ten days and incidence of intraventricular hemorrhage, patent ductus arteriosus, and socioeconomic status. Systematic observations were conducted on days 10, 20, and 30 after birth and at 36 and 40 weeks postconception. For the intervention infants, our observations were discussed with the infants' primary nurses, and individualized modifications for each infant's care plan were implemented based on these observations. Experimental infants showed significantly briefer stays on the respirator (P less than .01) and in increased FiO2 (P less than .05). Their feeding behavior was normalized significantly earlier (P less than .01). Experimental infants also showed significantly better behavioral regulation scores at 1 month after their mothers' estimated dates of confinement (post-EDC), as measured with the Assessment of Preterm Infants' Behavior, significantly better Mental and Psychomotor Developmental Indices at 3, 6, and 9 months post-EDC, as measured with the Bayley Scales of Infant Development, and significantly better behavioral regulation scores at 9 months post-EDC, as measured in a videotaped play observation. Measurements of weight, height, and head circumference at 3, 6, and 9 months post-EDC showed no differences. All assessments were performed by one of two trained testers not familiar with the goals of the study or the group status of the infant. These results support the hypothesis that very low birth weight preterm babies profit significantly both medically and developmentally from individualized behavioral care in the neonatal intensive care unit.

Bronchopulmonary Dysplasia

Age-related differences in brain electrical activity of healthy subjects.

A combined neurophysiological (electroencephalographic [EEG] and sensory evoked potential) and neuropsychological investigation was performed on 63 healthy men ranging in age from 30 to 80 years. Although alpha frequency diminished slightly with age, neither amplitude nor frequency demonstrated a high age correlation. Alpha blocking, in contrast, did correlate with age, in the direction of reduced alpha reactivity. EEG background activity underwent significant age-correlated change, consisting of reductions in slow activity and augmentation of fast activity, i.e., EEG desynchronization. Previously reported age-related EEG slowing may be related to the presence of disease in the populations studied. Topographic analysis revealed that the greatest change occurred in the temporal lobes. More change was noted either early or late in the age span, suggesting that aging is a nonlinear process. More features were derived from the right hemisphere than from the left, suggesting that the aging process is not completely symmetrical.

Adult

Brain electrical activity in patients with presenile and senile dementia of the Alzheimer type.

Neurophysiological and behavioral data obtained from 9 patients with presenile dementia and 10 with senile dementia of the Alzheimer type were compared with similar data from 25 age- and sex-equivalent controls. Compared with the healthy controls, both patients groups demonstrated increased background electroencephalographic slowing with a reduction in fast activity (synchronization). Topographic analyses of data from electroencephalographic and evoked potential studies indicate that areas of maximal group differences between the presenile patients and their controls include the right posterior temporal and, to a lesser extent, left midtemporal to anterior temporal areas, whereas the maximal differences between the senile patient group and their controls involve the midfrontal and anterior frontal lobes, bilaterally. Moreover, right-sided numerical features derived from topographic maps proved most useful in differentiating the presenile patients and their age-matched controls, whereas bilateral features were more useful in separating senile patients from their controls. These topographic dissimilarities between patient groups suggest that an age-disease interaction exists between patients with presenile and senile dementia of the Alzheimer type. Correlational analyses between neuropsychological test scores and neurophysiological features indicate that increased slowing and decreased fast activity were associated with poorer test performance.

Adult