PubMed Health⌕ Search

Biomedical subjects

B Dickerson

Publications and source records attributed to B Dickerson.

10 recordsLinked to original sources

Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease.

Atrophy of the hippocampal formation, a region important for the acquisition of new declarative knowledge, has been well-documented in Alzheimer's disease (AD), although the relation of such atrophy to the extent of memory dysfunction in these patients has been less clear. In the present study, 18 patients with a clinical diagnosis of probable AD were studied with a high-resolution, quantitative magnetic resonance imaging (MRI) protocol, as well as the verbal and spatial versions of the Buschke controlled learning task. The volumes of the hippocampal formation and, as a control for generalized atrophy, parahippocampal gyrus and temporal neocortex were computed from gapless coronal slices taken perpendicular to the long axis of the hippocampus. To correct for individual differences in brain size, volumes of regions of interest were divided by total intracranial volume. Separate stepwise regression analyses (with age, right and left hippocampal, parahippocampal gyrus, and temporal lobe volumes as the independent variables) showed that left hippocampal volume was the best predictor of free recall and delayed free recall of verbal information (P = 0.0042 and P < 0.0001, respectively). Recall and delayed recall of the spatial location of verbal items were best predicted by right hippocampal volume (P = 0.0054 and P = 0.0118, respectively). Memory scores did not correlate either with parahippocampal gyrus or temporal lobe volume. Furthermore, the relation between hippocampal volume and memory function observed in cases with AD did not hold for healthy aged control subjects.

Aged↗

From healthy aging to early Alzheimer's disease: in vivo detection of entorhinal cortex atrophy.

Using quantitative structural MRI protocols, we examined the effects of age on alterations in entorhinal cortex (EC) volume. The left EC was found to be smaller than the right in both young and healthy aged subjects. More importantly, the right EC, but not the left, was significantly smaller in elderly participants compared to young controls. In an attempt to determine the earliest sites of involvement in mild and incipient Alzheimer's disease (AD), we compared entorhinal and hippocampal volume in (1) healthy elderly controls, (2) patients with very mild AD, and (3) elderly patients who were evaluated for cognitive complaints, but did not meet criteria for dementia. Both patient groups differed from controls in EC volume, but not from each other. In contrast, the two patient groups differed in hippocampal volume from controls, as well as from each other, with the mild AD cases showing the greatest atrophy. These results suggest that degeneration of the EC and hippocampal formation occurs before the onset of overt dementia. In fact, follow-up clinical evaluations available on 23 of 28 nondemented patients indicated that 12 of 23 had converted to AD. Converters could be best differentiated from nonconverters on the basis of entorhinal volume.

Aging↗

Short-term distribution kinetics of intratracheally administered exogenous lung surfactant.

The short-term distribution kinetics of exogenous surfactant distribution after intratracheal instillation was investigated in surfactant-deficient neonatal piglets during assisted conventional mechanical ventilation and by high-frequency jet ventilation using exogenous calf lung surfactant extract (CLSE) labeled with 99mTc. Surfactant deficiency was induced by repeated bronchoalveolar lavage in piglets (1.2 +/- 0.4 kg, 1.4 +/- 0.7 d of age), and the short-term distribution kinetics of instilled, labeled CLSE were followed by gamma radioscintigraphy. Animals ventilated by either conventional mechanical ventilation or high-frequency jet ventilation showed similar improvement in arterial/alveolar oxygen ratios after surfactant replacement therapy (0.47 +/- 0.03 prelavage, 0.09 +/- 0.01 postlavage, 0.36 +/- 0.06 postsurfactant). This correlated directly with dynamic radioscintigraphic results showing that instilled CLSE began to distribute to the lungs within 5 s, and was present in substantial amounts in standardized symmetrical lung fields (central, right, and left; upper and lower) within 20 s of tracheal instillation. Subsequent measurements over 30 min showed continued presence of radiolabeled CLSE in all five areas of the lung, with no significant difference between conventional mechanical ventilation and high-frequency jet ventilation animals. Static (5-min) analyses at the end of this period showed that surfactant had distributed relatively symmetrically with 30% of the CLSE located in central regions, 40% in the upper lobes, and 30% in the lower lobes. In contrast, piglets receiving 99mTc in saline showed nonuniform distribution with multiple filling defects noted throughout the lungs. The rapid kinetics and ventilation independence of CLSE distribution suggest that surfactant spreading phenomena after tracheal instillation may facilitate the delivery of exogenous surfactant into aerated lungs in therapeutic applications.

Animals↗

Differential effects of oxygen and barotrauma on lung injury in the neonatal piglet.

In order to differentiate the effects of hyperoxia and barotrauma in the pathogenesis of acute neonatal lung injury, piglets were either hyperventilated (Paco2, 15-20 torr) for 48 hours with 100% oxygen (Group I), hyperventilated with 21% oxygen (Group II), normally ventilated (Paco2, 40-45 torr) with 100% oxygen (Group III), or normally ventilated with 21% O2 (Group IV) and compared to unventilated controls. Pulmonary function was tested, and biochemical indicators of lung injury were analyzed in tracheo-bronchial aspirates at 0, 24, and 48 hours. Bronchoalveolar lavage fluid was analyzed for surfactant composition and activity at the end of the study. At 48 hours, hyperoxic, hyperventilated piglets had significantly decreased dynamic lung compliance (30%) and increased pulmonary resistance (16%), aspirate cell count (190%), elastase activity (88%), albumin (214%), and total protein (150%) concentration. Qualitative light microscopy showed moderate to severe atelectasis, fibrinous exudate, edema, and inflammation. Normoxic, hyperventilated animals had comparable changes in pulmonary mechanics, but significantly milder cellular, biochemical, and morphologic changes. In hyperoxic, normocarbic animals pulmonary physiologic, cellular, and biochemical variables changed comparably to hyperoxic, hyperventilated animals; the pathologic changes were intermediate between hyperoxic, hyperventilated and normoxic, hyperventilated piglets. Normoxic, normocarbic animals had no significant changes in most variables over 48 hours; on morphologic examination their lungs were similar to unventilated controls and showed only mild edema. Surfactant had normal biophysical activity in all animals. Our results demonstrate that hyperoxia causes more significant physiologic, inflammatory, and histologic changes than barotrauma alone. Future attempts to prevent lung injury in neonates should be directed primarily at oxygen toxicity.

Acute Disease↗

Early pulmonary changes associated with high-frequency jet ventilation in newborn piglets.

To assess the short-term effects of high-frequency jet ventilation (HFJV) on the neonatal lung, 28 newborn piglets were studied. Nine piglets were unventilated except during brief pulmonary measurements, nine animals were conventionally ventilated (arterial CO2 tension 35-45 torr, arterial O2 tension 70-80 torr) for 4 h, and 10 piglets were ventilated with HFJV for the same period. Pulmonary function was analyzed using a computerized technique and tracheobronchial aspirates were examined for biochemical indicators of lung injury; after 4 h, bronchoalveolar lavage was obtained for surfactant composition and activity, and lung sections were examined by light and electron microscopy. Results showed that HFJV provided adequate ventilation at lower inspiratory pressure compared with conventional ventilation (8.6 +/- 0.3 versus 13.8 +/- 1.3 cm H2O; p less than 0.01), while pulmonary mechanics did not vary significantly among the three animal groups. Tracheobronchial aspirates from HFJV animals had higher elastase activity versus unventilated piglets (118.5 +/- 14.1 versus 57.7 +/- 8.4 micrograms/mL; p less than 0.01), as well as higher albumin concentration versus unventilated animals (94.2 +/- 18.7 versus 23.2 +/- 6.5 micrograms/mL; p less than 0.01). In addition, there were small but statistically significant differences between all three groups in the distribution of surfactant phospholipids in bronchoalveolar lavage, although biophysical activity was normal. Scanning electron microscopy revealed flattening of Clara cells in the terminal bronchioles of HFJV animals due to loss of glycogen and secretory granules. These data indicate that despite lower peak inspiratory pressures, HFJV can cause subtle biochemical changes in lungs. Further studies are indicated to determine if these changes precede significant lung injury.

Animals↗

Lung injury in the neonatal piglet caused by hyperoxia and mechanical ventilation.

Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury.

Animals↗

Determination of alkaline phosphatase in casein: collaborative study.

A collaborative study was made to determine alkaline phosphatase in casein samples by the rapid colorimetric test. Six to eight collaborators tested 10 unknown casein samples containing various amounts of residual phosphatase with and without the addition of magnesium acetate. Results indicated that magnesium acetate significantly increased phosphatase activity. The collaborators correctly analyzed 95% of the samples with the added magnesium acetate. The method has been adopted official first action.

Alkaline Phosphatase↗