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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1997

Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons.

OBJECTIVE: The purpose of this study was to test the hypothesis that abnormalities in the parvalbumin-containing subclass of local circuit neurons contribute to altered gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex of schizophrenic subjects. METHOD: Profile counts and somal size measures were made of parvalbumin-immunoreactive neurons in areas 9, 46, and 17 from 15 matched pairs of schizophrenic and normal comparison subjects. RESULTS: No differences in relative density, laminar distribution, or somal size of labeled neurons were found in any region. CONCLUSIONS: These findings suggest that altered GABA neurotransmission in schizophrenia is due to either abnormalities in other sub-populations of prefrontal cortical GABA neurons or abnormalities in the parvalbumin-containing subclass that could not be detected in the present study.

Cell Count↗
PubMed1996

Patterns of intrinsic and associational circuitry in monkey prefrontal cortex.

Both local and long-range connections are critical mediators of information processing in the cerebral cortex, but little is known about the relationships among these types of connections, especially in higher-order cortical regions. We used quantitative reconstructions of the label arising from discrete (approximately 350 microns diameter) injections of biotinylated dextran amine and cholera toxin B to determine the spatial organization of the axon collaterals and principal axon projections furnished by pyramidal neurons in the supragranular layers of monkey prefrontal cortex (areas 9 and 46). Both terminals and cell bodies labeled by transport along axon collaterals in the gray matter formed intrinsic clusters which were arrayed as a series of discontinuous stripes of similar size and shape. The co-registration of anterograde and retrograde transport confirmed that these convergent and divergent intrinsic connections also were reciprocal. Transport from the same injection sites along principal axons through the white matter formed associational clusters which were also arrayed as a series of discontinuous stripes. The dimensions of the anterogradely- and retrogradely-labeled associational stripes were very similar to each other and to the intrinsic stripes. These findings demonstrate that divergence, convergence, and reciprocity characterize both the intrinsic and associational excitatory connections in the prefrontal cortex. These patterns of connections provide an anatomical substrate by which activation of a discrete group of neurons would lead to the recruitment of a specific neuronal network comprised of both local and distant groups of cells. Furthermore, the consistent size of the intrinsic and associational stripes (approximately 275 by 1,800 microns) suggests that they may represent basic functional units in the primate prefrontal cortex.

Animals↗
PubMed1996

Marshmallows cause an outbreak of infection with Salmonella enteritidis phage type 4.

Thirty-six cases of Salmonella enteritidis phage type (PT) 4 infection, mainly in children, were notified in one local authority in the two weeks beginning on 23 October 1995. Twenty-four cases and 42 controls nominated by cases were included in a case control study, which showed a significant association between illness and the consumption of marshmallow confectionery from a bakery. S. enteritidis PT4 was isolated from samples of the marshmallow, and all isolates had the same plasmid and pulsed field gel electrophoresis profiles. The marshmallow had been made using raw egg white, which shows that not all caterers follow the Department of Health's advice.

Case-Control Studies↗
PubMed1996

The hierarchical development of monkey visual cortical regions as revealed by the maturation of parvalbumin-immunoreactive neurons.

The prefrontal cortex is known to be involved in behavioral paradigms requiring decisions based on short-term working memory, and visually related areas of prefrontal cortex represent the final point in a proposed hierarchical sequence of visual signal processing that begins in primary visual cortex. This study asks if the development of at least certain aspects of the circuitry of each region involved in this hierarchy proceeds in a sequential fashion from primary to higher-order areas. The timing and patterns of expression of immunoreactivity for the calcium-binding protein parvalbumin were examined in areas V1, V2, TE, 7a, and 46 in two series of macaque monkeys ranging in age from embryonic day 132 to adult. The number and laminar distribution of parvalbumin-labeled neurons reached adult levels first in area V1 (primary visual cortex), followed by the adjacent visual association area V2, and then by the higher-order regions of the inferior temporal (TE), posterior parietal (7a) and prefrontal (46) cortices. The appearance of parvalbumin immunoreactivity in the axons of the two major classes of local circuit neurons that express this protein, basket and chandelier cells, followed a similar regional pattern. Furthermore, striking differences were present between these two neuronal populations in the laminar pattern and time course of parvalbumin labeling of their axons. These findings demonstrate that at least some aspects of the intrinsic circuitry of the neocortex mature in accordance with a functional hierarchy of cortical regions. In addition, they illustrate the complexity of cortical development in terms of the different timing of expression of even a single protein in different compartments within single neurons, in different cell types, in different laminae within a region, and across different cortical regions.

Animals↗
PubMed1996

Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections.

We have examined the biochemical and histological effects of high concentrations of dopamine (0.05-1.0 micromol) injected into the rat striatum. Twenty-four hours after such injections, the oxidation products of dopamine and dihydroxyphenylacetic acid were detected as both free and protein-bound cysteinyl dopamine and cysteinyl dihydroxyphenylacetic acid. Protein-bound cysteinyl catechols were increased 7- to 20-fold above control tissue levels. By 7 days postinjection, the protein-bound cysteinyl catechols were still detectable, although reduced in concentration, whereas the free forms could no longer be measured. Histological examination of striatum at 7 days revealed a central core of nonspecific damage including neuronal loss and gliosis. This core was surrounded by a region containing a marked reduction in tyrosine hydroxylase immunoreactivity but no apparent loss of serotonin or synaptophysin immunoreactivity. When dopamine was injected with an equimolar concentration of either ascorbic acid or glutathione, the formation of protein-bound cysteinyl catechols was greatly reduced. Moreover, the specific loss of tyrosine hydroxylase immunoreactivity associated with dopamine injections was no longer detectable, although the nonspecific changes in cytoarchitecture were still apparent. Thus, following its oxidation, dopamine in high concentrations binds to protein in the striatum, an event that is correlated with the specific loss of dopaminergic terminals. We suggest that the selective degeneration of dopamine neurons in Parkinson's disease may be caused by an imbalance between the oxidation of dopamine and the availability of antioxidant defenses.

Animals↗
PubMed1996

Magnopyramidal neurons in the anterior motor speech region. Dendritic features and interhemispheric comparisons.

OBJECTIVE: To test the hypothesis that the larger somal size of layer III magnopyramidal neurons in left than in right Brodmann area 45 is associated with greater measures of dendritic arborization in the left hemisphere neurons. DESIGN: A case series involving postmortem human brain specimens was used to compare dendritic parameters of Golgi-impregnated layer III pyramidal neurons in Brodmann area 45 in the left and right hemispheres. SUBJECTS: A convenience sample consisting of 9 subjects with no known neurologic or psychiatric disorders was obtained at autopsy. MAIN OUTCOME MEASURES: Dendritic parameters of the 10 largest Golgi-impregnated layer III pyramidal neurons were measured in each hemisphere of each brain using a eutectic neuron tracing system. The measures examined were somal size, neuron depth, mean segment length, number of branch points, maximal branch order, combined dendritic diameter, total dendritic length, horizontal extent of the dendritic field, and spine density. The Golgi-impregnated slides were also compared with Nissl-stained slides from adjacent blocks to determine the laminar location of the sampled neurons. RESULTS: Although the mean somal size was greater in the left than in the right hemisphere, none of the dendritic parameters examined was larger for the left hemisphere neurons. As expected, total dendritic length was positively correlated to somal size (r = 0.43, P < 001) in the left hemisphere. However, there was no correlation between these parameters in the right hemisphere (r = 0.02, P = .76). CONCLUSIONS: The difference between left and right Brodmann area 45 magnopyramidal neurons in the correlation of somal size and dendritic length provides additional evidence of anatomical differences between these 2 populations of neurons. However, the lack of interhemispheric differences in measures of dendritic arborization suggests that additional factors contribute significantly to the marked difference in somal size between the large magnopyramidal neurons in the left and right hemispheres.

Adult↗
PubMed1996

Effects of D2 dopamine receptor antagonists on Fos protein expression in the striatal complex and entorhinal cortex of the nonhuman primate.

Recent studies have reported that acute administration of dopamine D2 receptor antagonists increases expression of the immediate early gene c-fos in the rat striatal complex. There have been no corresponding studies of the effects of D2 antagonists in primate species. Since all clinically effective antipsychotic drugs share D2 receptor antagonism, it is important to define the extent to which these drugs may alter expression of c-fos or its protein product, Fos, in primates. We therefore examined the effects of administration of two D2 receptor antagonists, haloperidol and metoclopramide, on Fos expression in the striatum and temporal cortices of the vervet monkey. Metoclopramide does not appear to possess significant antipsychotic efficacy but potently produces extra-pyramidal side effects, while haloperidol is an effective antipsychotic drug that produces extrapyramidal side effects. Both drugs increased the number of Fos-like immunoreactive (Fos-li) neurons in the caudate nucleus and putamen; the numbers of Fos-li neurons in these regions were increased in both the patch and matrix compartments. Haloperidol but not metoclopramide increased the number of Fos-li neurons in the nucleus accumbens shell. Similarly, haloperidol but not metoclopramide increased the number of Fos-li neurons in the entorhinal cortex. Neither drug altered Fos expression in the inferior temporal cortex. These data suggest that the dorsolateral caudate nucleus and putamen may be sites at which D2 receptor antagonists elicit extrapyramidal side effects, and the nucleus accumbens shell and entorhinal cortex may be loci at which the therapeutic actions of antipsychotic drugs are manifested.

Animals↗
PubMed1996

Aprotinin improves outcome of single-ventricle palliation.

BACKGROUND: Elevation of pulmonary vascular resistance as a consequence of cardiopulmonary bypass may lead to failure of single-ventricle palliation. We reviewed our experience with aprotinin, a nonspecific serine protease inhibitor, to determine whether it could ameliorate the inflammatory effects of cardiopulmonary bypass and improve outcome of single-ventricle palliation. METHODS: Forty-six consecutive patients undergoing single-ventricle palliation using cardiopulmonary bypass were reviewed retrospectively. Aprotinin was used in 8 of 30 bidirectional cavopulmonary shunt and 10 of 16 Fontan procedures. RESULTS: Aprotinin use was associated with a decrease in the early postoperative transpulmonary gradient among patients undergoing Fontan and bidirectional cavopulmonary shunt procedures. The bidirectional cavopulmonary shunt aprotinin group had a higher oxygen saturation and a decrease in quantity and duration of thoracic drainage. Among patients receiving aprotinin there were no episodes of mediastinitis, thrombus formation, or renal failure. CONCLUSIONS: Aprotinin use in single-ventricle palliation was associated with decreased transpulmonary gradient and increased oxygen saturation consistent with decreased pulmonary vascular resistance. This retrospective study suggests that aprotinin has a favorable impact on the early postoperative course of single-ventricle palliation.

Aprotinin↗
PubMed1996

Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects.

Recent studies have suggested that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transient but essential structure in the formation of cerebral cortical circuitry. Although most subplate neurons die during later development, some remain as the interstitial neurons of the adult white matter. In this study we used a monoclonal antibody against the cytoskeletal protein, microtubule associated protein-2 (MAP2), to quantify the density and distribution of labeled neurons in postmortem brain specimens containing the prefrontal white matter from five schizophrenic cases and matched controls. In both schizophrenics and matched controls, the density of white matter neurons decreased with increasing white matter depth. However, the mean density of MAP2-immunoreactive neurons was greater in the superficial white matter of the schizophrenic subjects compared to the matched controls. In contrast, no difference in the density of labeled neurons was seen in the deeper white matter. These findings are consistent with an abnormality in the development of the cortical subplate in at least some cases of schizophrenia.

Adult↗
PubMed1996

The effect of pre-ECLS ventilation time on survival and respiratory morbidity in the neonatal population.

Although mechanical ventilation for more than 7 to 10 days has been considered a contraindication to the application of extracorporeal life support (ECLS) in neonates, the outcome and respiratory morbidity for newborns placed on ECLS after more than 7 days of ventilation have not been well characterized. The purpose of this study was to determine the impact of pre-ECLS ventilation time on the rate of survival, the likelihood of the development of bronchopulmonary dysplasia (BPD), and the need for supplemental oxygen at the time of discharge. Examination of the Extracorporeal Life Support Organization (ELSO) Registry showed that 6,110 neonates were treated for respiratory failure with a pre-ECLS ventilation time of less than 14 days between January 1990 and May 1995. Gestational age (GA), birth weight (BW), indication for ECLS, and diagnosis were compared with the rate of survival, the discharge diagnosis of BPD, and the need for home oxygen. The GA and BW of neonates placed on ECLS during the first week of life (n = 5,888) did not differ significantly from those of neonates whose ECLS was begun in the second week of life (n = 222). The neonates were divided into two groups (early, ventilation time of 3 to 6 days; late, ventilation time of 7 to 10 days) to determine the odds ratios for survival, BPD, and home oxygen. Logistic regression analysis was used to develop a model to predict the rate of survival, the risk for the development of BPD, and the need for home oxygen given the length of pre-ECLS ventilation time. The late group was less likely to survive (odds ratio, 1.8; 95% confidence interval [CI], 1.21 to 2.68). The late group also had approximately twice the risk for the development of BPD (odds ratio, 1.9; 95% CI, 1.2 to 3.04) and a trend toward an increased incidence of home oxygen use (odds ratio, 1.55; 95% CI, 0.92 to 2.60). The authors conclude that (1) there is a greater risk of mortality and BPD and a trend toward an increased need for home oxygen with increased time on the ventilator before ECLS; (2) at 14 days the predicted probability of survival is still 53% (95% CI, 31% to 74%); (3) at 14 days the predicted probability of BPD is 54% (95% CI, 28% to 78%); and (4) based on these data, it is reasonable to consider application of ECLS to patients who have had mechanical ventilation for up to 14 days.

Bronchopulmonary Dysplasia↗
PubMed1996

The incidence and epidemiology of beta-lactam resistance in Haemophilus influenzae.

Consecutive isolates of Haemophilus influenzae were collected by the Public Health Laboratory, Bath between 1 June 1992 and 31 May 1993. Of 379 apparently distinct isolates, 216 originated from the respiratory tract, 102 from eyes and 61 from other sites. The minimum inhibitory concentrations of amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime and cefpodoxime were determined for each isolate. Forty strains (10.6%) were beta-lactamase producers. MIC50 and MIC90 values and the range of MICs were determined for all isolates. The overall resistance rates were: amoxycillin (MIC > 1.0 mg/L), 22.7%; amoxycillin/clavulanate (MIC > 1.0 mg/L), 14.8%; cefuroxime (MIC > 1.0 mg/L), 18.5%, (MIC > 4.0 mg/L), 5.5%; cefaclor (MIC > 8 mg/L), 15.6%; cefpodoxime (MIC > 1.0 mg/L), 0.3%; cefotaxime (MIC > 1.0 mg/L), 0%. Twenty non-beta-lactamase producing but beta-lactam resistant strains (cefuroxime MIC > 4.0 mg/L) were matched with 20 susceptible strains on the basis of patient age, sex, and specimen type. The strains were characterised by outer-membrane protein (OMP), random amplified polymorphic DNA (RAPD) and ribotyping patterns. Eleven of the 20 resistant strains were indistinguishable by the methods used, suggesting spread of a single beta-lactam resistant, non-beta-lactamase producing clone. The distribution of resistant strains within the local community was plotted geographically.

Adolescent↗
PubMed1996

Verapamil sensitive incessant ventricular tachycardia in the newborn.

Incessant VTs in infancy are often poorly tolerated. Response to conventional antiarrhythmic therapy is disappointing. The present case involves a 3-week-old infant with an incessant VT of a left bundle branch block, and normal axis morphology. This tachycardia was inducible with both atrial and ventricular pacing, but not by premature stimulation. Tachycardia persisted despite treatment with adenosine, esmolol, procainamide, and flecainide. Intravenous verapamil suppressed tachycardia and prevented inducibility, and no further recurrences were seen on oral verapamil. This case suggests that some incessant VTs in infancy may be due to calcium channel related afterdepolarizations or triggered activation.

Anti-Arrhythmia Agents↗