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Biomedical subjects

J Moossy

Publications and source records attributed to J Moossy.

At least 37 records · Page 2Linked to original sources
PubMed1989

Diagnosis of dementia: clinicopathologic correlations.

Based on 54 demented patients consecutively autopsied at the University of Pittsburgh, we studied the accuracy of clinicians in predicting the pathologic diagnosis. Thirty-nine patients (72.2%) had Alzheimer's disease, while 15 (27.7%) had other CNS diseases (four multi-infarct dementia; three Creutzfeldt-Jakob disease; two thalamic and subcortical gliosis; three Parkinson's disease; one progressive supranuclear palsy; one Huntington's disease; and one unclassified). Two neurologists independently reviewed the clinical records of each patient without knowledge of the patient's identity or clinical or pathologic diagnoses; each clinician reached a clinical diagnosis based on criteria derived from those of the NINCDS/ADRDA. In 34 (63%) cases both clinicians were correct, in nine (17%) one was correct, and in 11 (20%) neither was correct. These results show that in patients with a clinical diagnosis of dementia, the etiology cannot be accurately predicted during life.

Adult↗
PubMed1988

Bilateral symmetry of morphologic lesions in Alzheimer's disease.

We studied 16 brains of patients with Alzheimer's disease for left-right differences, or similarities, in the density of senile plaques (SPs) or neurofibrillary tangles (NFTs). Counts were made of SPs and NFTs on the left and right side of five different brain areas, which included middle frontal, superior temporal, the prosubiculum of the hippocampus (HPR), the entorhinal cortex of the hippocampus (HEN), and the basal nucleus of Meynert. The density of SPs was bilaterally symmetrical in all regions except the basal nucleus of Meynert in which technical problems may have occurred in sampling. In contrast to SPs, the density of NFTs was bilaterally symmetrical in both neocortical regions (middle frontal, superior temporal), but not in either hippocampal region (HPR, HEN). The absence of bilateral symmetry for the density of NFTs in the hippocampus, where the density of SPs was highly symmetrical, suggests that there may be a different pathogenesis for these lesions in Alzheimer's disease. The lack of a significant correlation between SP and NFT density within four of five regions, including HPR and HEN, also supports this suggestion.

Aged↗
PubMed1988

Bilateral symmetry of cholinergic deficits in Alzheimer's disease.

The specific activities of the cholinergic enzymes, choline acetyltransferase and acetylcholinesterase, as well as the density of muscarinic binding sites, were determined in five corresponding left and right regions of 16 brains obtained at autopsy from patients with histologically confirmed Alzheimer's disease. While a significant proportion of the individual specimens exhibited left-right asymmetries in cholinergic deficits, bilateral symmetry was the rule for frontal and temporal cortex, basal nucleus, and the prosubiculum of the hippocampus. In contrast to these four regions, left-right asymmetries in choline acetyltransferase activity and muscarinic receptor density appeared to be typical in the entorhinal cortex of the hippocampus.

Acetylcholinesterase↗
PubMed1988

Correlation of phosphorus-31 magnetic resonance spectroscopy and morphologic findings in Alzheimer's disease.

Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.

Aged↗
PubMed1988

Major depression in primary dementia. Clinical and neuropathologic correlates.

Cytopathologic features were quantified in seven brain regions in the brains of 37 demented patients, with or without major depression, and in those of seven controls with no history of dementia or depression. The middle frontal and superior temporal cortex, prosubiculum and entorhinal cortex of the hippocampus, nucleus basalis of Meynert, locus ceruleus, and substantia nigra were the areas evaluated. Patients with major depression had significantly more degenerative findings in the locus ceruleus and substantia nigra than demented patients who were not depressed. In contrast, these groups were similar with respect to other clinical features and indexes of global severity of dementia. A logistic regression model that included the degenerative features of both the locus ceruleus and the substantia nigra was significantly better at predicting the presence of major depression than those employing the characteristics of either pigmented nucleus alone. Our results indicate that the development of major depression in patients with primary dementia is associated with the degeneration of the locus ceruleus and substantia nigra.

Aged↗
PubMed1988

Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome.

Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.

Animals↗
PubMed1988

31P nuclear magnetic resonance study of the brain in Alzheimer's disease.

The histopathological hallmarks of Alzheimer's disease have long been considered to be neurofibrillary tangles (NFT) and neuritic (senile) plaques (SP). Neither of these structures, however, are unique to Alzheimer's disease, and both probably represent end-stage markers of the disorder. NFT have been demonstrated in many disorders; SP occur in small numbers with normal aging. Evidence is presented for elevation of phosphomonoesters (PME) in Alzheimer's brain compared to non-Alzheimer's diseased controls and normal controls. The PME detected by 31P nuclear magnetic resonance (NMR) spectroscopy of autopsy brain are predominantly anabolic precursors of membrane phospholipids. Elevated PME could be secondary to a metabolic block at the rate-limiting enzyme in membrane phospholipid synthesis, which is cytidine triphosphate (CTP): phosphocholine (or phosphoethanolamine) cytidyltransferase (EC 2.7.7.15). Elevated PME could also be secondary to decreased breakdown of PME by phospholipase D activity. Since CTP: phosphocholine cytidyltransferase is inactivated by phosphorylation and since there is independent evidence for hyperphosphorylation of tau and MAP-2 proteins in AD brain, enhanced protein kinase activity could be a common factor. Preliminary evidence suggests that PME could interact with N-methyl-D-aspartate receptors and potentially act as false neurotransmitters. Further studies will be needed to investigate these possibilities.

Aged↗
PubMed1988

Normal perivascular spaces mimicking lacunar infarction: MR imaging.

Perivascular (Virchow-Robin) spaces normally surround perforating arteries that enter the medial temporal lobes, corpus striatum, and thalamus. The high soft-tissue sensitivity of magnetic resonance (MR) imaging allows for the frequent detection of such cerebrospinal fluid (CSF)-filled spaces. Especially on axial images, these CSF-filled perivascular spaces may be confused with pathologic lesions, such a lacunar infarcts. Postmortem brain specimens demonstrate the anatomy of perivascular spaces around perforating arteries. Orthogonal images in the living patient help confirm this anatomic relationship. The characteristic CSF signal patterns from these foci are further evidence of their anatomic identification and true benign nature.

Brain↗
PubMed1988

Stable xenon enhanced computed tomography in the study of clinical and pathologic correlates of focal ischemia in baboons.

When the lateral striate arteries of baboons are occluded, an immediate cessation of blood flow followed by a transient, minimal restitution of flow occurs in that vascular distribution. These findings are evident from serial xenon/computed tomography cerebral blood flow imaging. In our study, infarction consistently accompanied arterial occlusion for 6 hours or more. The xenon/computed tomography method provides a sensitive, noninvasive technique for examining sequential alterations of cerebral blood flow in small regions deep within the brain. This methodology for recording cerebral blood flow permits correlative studies of cerebral infarction, clinically and experimentally, and allows reasonable inferences about the probabilities of neural tissue damage.

Animals↗
PubMed1987

Thalamic and subcortical gliosis with dementia.

We describe two cases of patients with "primary dementia" in whom autopsy showed marked astrocytosis in several subcortical nuclei, but chiefly in those of the thalamus. One patient had the onset of symptoms at 31 years of age and a subacute course. The second patient was an elderly man with a strong familial history of dementia. These cases offer further evidence that subcortical lesions, especially in the thalamus, may produce a dementia that is not always clinically distinguishable from Alzheimer's disease and other "cortical" dementias.

Adult↗
PubMed1986

Hyperoxia produces neuronal necrosis in the rat.

Widespread cerebral neuronal necrosis occurred in newborn Sprague-Dawley rats submitted to three hours of pure oxygen (100% O2) at normal atmospheric pressure. Neuronal necrosis (NN) was most severe in the immediate newborn period and less marked with advanced maturation. It was minimal and different in its morphological characteristics in rats 10, 15 and 20 days old, and in adults breathing pure oxygen at normal atmospheric pressure for three hours. In the newborn rat, hyperoxemic NN was different in topography and cytopathology from that induced by hypoxia in the same animals. Hyperoxemic NN was similar to the NN described in human premature infants submitted to episodic hyperoxemia. Neuronal damage with karyorrhexis was most prominent in the subiculum of the hippocampus, thalamus, reticular nuclei of the brain stem and the granular cells of the cerebellum. Ultrastructural studies demonstrated nuclear and cytoplasmic membrane damage in neurons and the cellular accumulation of electron-dense lipid droplets. The pathogenesis of NN produced by hyperoxia in the human premature newborn infant may be related to lipid peroxidation of cell membranes such as that induced by oxygen-free radicals in other experimental and in vitro studies, when the anti-oxidant cellular defenses (mainly enzymes such as superoxide dismutase) are overwhelmed.

Animals↗
PubMed1985

The dissolution of language in Pick's disease with neurofibrillary tangles: a case study.

This paper is a detailed retrospective history of a patient who began to have difficulty with speaking and comprehension in 1967, and whose neuropathological examination at time of death 12 1/2 years later was consistent with a diagnosis of Pick's disease, complicated by neurofibrillary tangles. It follows the deteriorating course of his language abilities in the context of relatively less-impaired general cognitive abilities, using two sources of information. The first is his own written record of his deteriorating abilities, shown in letters and notes he wrote over this period. The second is through an oral history obtained from the patient's family. The purpose of this report is to illustrate in detail the course of a degenerative condition and to suggest the utility of such descriptional records in increasing understanding of language deterioration in dementia.

Aged↗
PubMed1984

Thiopental treatment after global brain ischemia in pigtailed monkeys.

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Prolonged immobilization and controlled ventilation do not improve outcome after global brain ischemia in monkeys.

This study is a therapeutic evaluation of prolonged immobilization and controlled intermittent positive-pressure ventilation (IPPV) after global brain ischemia (GBI) in pigtailed monkeys. Sixteen min of GBI was produced with a high-pressure neck cuff, while the lungs were being continuously ventilated. Normotension was restored within 2 min postischemia (PI). The control group of 13 monkeys was weaned from IPPV 4 to 6 h PI. The treatment group of 18 animals was paralyzed and ventilated with a 50:50 nitrous oxide-oxygen mixture for 48 h PI. Intensive care was maintained for 96 h PI. In the control group, 8 of 10 animals were awake at 96 h PI compared to 7 of 11 in the treatment group. Neurologic deficit scores for the survivors in the 2 groups were also not significantly different. Histologic examination supported this conclusion. Paralysis/IPPV for 48 h post-GBI with 50% N2O facilitates control of blood gases and blood pressure, but does not improve the neurologic outcome over that achieved with only 4 to 6 h controlled ventilation.

Animals↗
PubMed1984

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.

Animals↗