Search PubMed⌕ Search

Biomedical subjects

A J Dwork

Publications and source records attributed to A J Dwork.

At least 19 recordsLinked to original sources
PubMed1999

Application of cognitive scales to medical records of schizophrenia inpatients.

The Scales of Cognitive Impairment Rated From Institutional Records (SCIRFIR), a battery based on commonly used dementia rating instruments, was tested on the records of 26 chronically institutionalized, elderly schizophrenia patients, for the purpose of retrospectively evaluating the long-term course of cognitive change in schizophrenia and relating it to available autopsy materials. The inter-rater reliability of the component scales was high (Intraclass Correlations = 0.78-0.96), the final item scores were comparable to ratings on living subjects, and Alzheimer-type neuropathological changes were associated with a markedly deteriorating course. The substantial potential of this method is discussed.

Aged↗
PubMed1999

Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness.

Abnormalities of proteins involved in neurotransmission and neural plasticity at synapses are reported in schizophrenia, and may be markers of dysregulated neural connectivity in this illness. Studies of brain development and neural regeneration indicate a dynamic interplay between neural and oligodendroglial mechanisms in regulating synaptic plasticity and axonal sprouting. In the present study, markers of synapses (synaptophysin), plasticity (growth-associated protein-43) and oligodendrocytes (myelin basic protein) were investigated in anterior frontal cortex homogenates from individuals with schizophrenia and depression. Synaptophysin immunoreactivity was reduced in schizophrenics who died of natural causes relative to controls. Myelin basic protein immunoreactivity was decreased in both schizophrenics and depressed individuals who died by suicide. Overall, no changes were observed in growth-associated protein-43 immunoreactivity. However, a slight increase in immunoreactivity in depressed suicides relative to control was observed. These findings support the hypothesis that synaptic abnormalities are a substrate for disordered connectivity in severe mental illness, and suggest that synaptic-oligodendroglial interactions may contribute to the mechanism of dysregulation in certain cases.

Adult↗
PubMed1998

Senile degeneration and cognitive impairment in chronic schizophrenia.

OBJECTIVE: This study was an investigation of the role of Alzheimer-type senile degenerative abnormalities in the cognitive impairment of chronic schizophrenia. METHOD: The study group comprised 145 deceased elderly institutionalized psychiatric patients: 66 with schizophrenia, 26 with mood disorders, 36 with dementia, and 17 with other psychiatric diagnoses. The comparison group included 16 deceased elderly individuals without neurologic or psychiatric disease. Psychiatric diagnoses and cognitive status were established by standardized review of medical records. Neuritic senile plaques and neurofibrillary tangles were identified immunohistochemically and counted, by investigators blind to clinical information, in standardized regions of each brain. RESULTS: Of the subjects with schizophrenia, 68% had definite cognitive impairment, but only 8% satisfied neuropathological criteria for Alzheimer's disease. Among the schizophrenia subjects without Alzheimer's disease, definite cognitive impairment was associated with higher levels of plaques and tangles. The schizophrenia subjects without definite cognitive impairment had fewer plaques and tangles than the unimpaired nonpsychiatric subjects. CONCLUSIONS: Most cases of cognitive impairment in schizophrenia could not be attributed to Alzheimer's disease. An association of mild Alzheimer-type pathology with definite cognitive impairment was unique to schizophrenia. Enhanced sensitivity to the effects of aging on the brain may be a manifestation of diminished cognitive reserve in schizophrenia.

Aged↗
PubMed1997

Postmortem studies of the hippocampal formation in schizophrenia.

Many postmortem studies report differences between the hippocampal formations of patients with schizophrenia and those of controls. These differences include volume changes, cell density changes, periventricular gliosis, senile degenerative changes, and abnormalities of neuronal size, position, or orientation. However, the findings are almost never common to all schizophrenia patients within a series. Furthermore, some well-designed studies are negative, and different positive reports are mutually contradictory. Some of the inconsistencies are methodological. The normal variation, over small distances, in the cytoarchitecture of the temporal allocortex creates particular difficulties when this region is studied with a limited number of sections, especially if the sample size is small. Other inconsistencies are probably the result of case selection. We review the methods and findings of some of these studies, stressing the dangers of eliminating (rather than evaluating) cases with definite neuropathologic changes. We conclude that the existing postmortem studies of temporal lobe morphology provide little conclusive evidence for the neural substrate of schizophrenia.

Hippocampus↗
PubMed1995

Effects of diet and development upon the uptake and distribution of cerebral iron.

In order to determine whether iron sequestered by the rat brain during the third week of postnatal life could be mobilized by subsequent dietary iron deficiency (ID), iron-59 (59Fe) was administered to rats at 2 weeks of age. The animals were placed on an ID or a control diet from age 4 through 8 weeks and killed by perfusion. Brain radioactivity was identical for both groups, and autoradiography revealed no differences in the distribution of radioactivity. Thus, neither the sequestration of cerebral iron acquired at age 2 weeks nor its subsequent redistribution was affected by ID. Since ID beginning after age 3 weeks reportedly produces a cerebral iron deficit that is in part reversible, an attempt was made to determine whether 59Fe administered after ID was preferentially delivered to any brain region. Rats were placed on an ID or a control diet from age 3 through 7 weeks and then injected with 59Fe, placed on a normal diet, and killed 2 weeks later. Thre was no difference between groups in amount or distribution of brain 59Fe, except in the choroid plexus, which was more radioactive in the ID rats than in the controls. This finding may represent a mechanism by which the choroid plexus buffers the brain against rapid rises in plasma iron content.

Animals↗
PubMed1995

Rapidly progressive frontal-type dementia associated with Lyme disease.

The authors report a case of fatal neuropsychiatric Lyme disease (LD) that was expressed clinically by progressive frontal lobe dementia and pathologically by severe subcortical degeneration. Antibiotic treatment resulted in transient improvement, but the patient relapsed after the antibiotics were discontinued. LD must be considered even in cases with purely psychiatric presentation, and prolonged antibiotic therapy may be necessary.

Aged↗
PubMed1994

Does ECT alter brain structure?

OBJECTIVE: The purpose of this study was to evaluate whether ECT causes structural brain damage. METHOD: The literature review covered the following areas: cognitive side effects, structural brain imaging, autopsies of patients who had received ECT, post-mortem studies of epileptic subjects, animal studies of electroconvulsive shock (ECS) and epilepsy, and the neuropathological effects of the passage of electricity, heat generation, and blood-brain barrier disruption. RESULTS: ECT-induced cognitive deficits are transient, although spotty memory loss may persist for events immediately surrounding the ECT course. Prospective computerized tomography and magnetic resonance imaging studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodified ECT era reported cerebrovascular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion fixation techniques were employed. Controlled studies using quantitative cell counts have failed to show neuronal loss even after prolonged courses of ECS. Several well-controlled studies have demonstrated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity in primates, and adequate muscle paralysis and oxygenation further delay these changes. These conditions are not approached during ECT. Other findings indicate that the passage of electricity, thermal effects, and the transient disruption of the blood-brain barrier during ECS do not result in structural brain damage. CONCLUSIONS: There is no credible evidence that ECT causes structural brain damage.

Adult↗
PubMed1993

Alzheimer-type neuropathology in elderly schizophrenia patients.

Traditionally, schizophrenia has been studied in early adulthood. Its course and outcome during senescence are largely unknown and subject to controversy. We reviewed the consecutive neuropathologic records of 1,046 patients who were chronically hospitalized in New York State mental institutions, and we selected for analysis all 802 patients who died after age 50 with a clinical antemortem diagnosis, as recorded in the autopsy notes, of schizophrenia (n = 544) or dementia (n = 258). The prevalence of neuropathologic diagnoses consistent with Alzheimer's disease (AD) was 51 percent in the dementia group and 28 percent in the schizophrenia sample. This prevalence rate in the schizophrenia sample (mean age = 77) was considerably higher than that estimated for the general population. When evaluated against age of death, AD findings in demented patients were age invariant, whereas the rate of such findings in schizophrenia patients rose monotonously from under 5 percent below age 60 to 50 percent at age 90 and over. The age-relative rate of AD diagnosis in schizophrenia patients was similar to a curve postulated for first-degree relatives of familial AD patients and was markedly higher than population estimates. These findings as a basis for comparison with other retrospective studies of pathological records are presented. Our own study, as well as others, suffers from three intrinsic limitations. The clinical diagnoses are taken from death notes and have no formal verification. Likewise, neuropathologic diagnoses were based upon informal criteria in use at the time; since that time, formal diagnostic criteria have been evolving, and new staining methods have become available. Finally, it is not possible to determine from this material whether these patients are representative of all elderly schizophrenia patients or even of those who are institutionalized. Therefore, despite the large sample size on which our current findings are based, a new study has begun to address these weaknesses by complete review and rediagnosis of medical records and neuropathological material, using current methods, standardized criteria, and quantitative measures of degenerative changes. Specifically, the new ongoing study examines whether autopsied patients are representative by performing detailed diagnostic reviews of a control sample of nonautopsied patients from the same institutions. These results, if confirmed in the new study, demonstrate substantially greater vulnerability of chronic schizophrenia patients to the development of AD (or, at least, to histological changes typical of this disease). Possible association with chronic neuroleptic treatment and pathophysiological mechanisms remains to be elucidated.

Adult↗
PubMed1993

Dominantly inherited, early-onset parkinsonism: neuropathology of a new form.

We report postmortem findings in a 46-year-old man with dominantly inherited parkinsonism whose symptoms started at age 28. At least 13 other family members in three generations have been affected, some from early childhood. Dystonia is a prominent feature in several of the youngest patients, but was not present in this patient. After several years of successful treatment with medication, he developed severe on-off fluctuations and dyskinesias. At age 45, the patient underwent stereotaxic implantation of autologous adrenal medullary tissue into the left corpus striatum and lateral ventricle. He improved considerably over the following 6 months, but then developed glioblastoma multiforme and died 1 year after transplantation. There was severe neuronal loss in the pars compacta and pars reticulata of the substantia nigra, with prominent gliosis in the pars reticulata. The nigral neurons remaining in the pars compacta were poorly pigmented. Neither Lewy bodies nor neurofibrillary tangles were present, and we identified no other degenerative neuropathologic changes. This combination of pathologic and clinical features differs from any previously reported case.

Adult↗
PubMed1993

Late-onset Lafora's disease with typical intraneuronal inclusions.

We describe a patient with progressive myoclonus epilepsy (late-onset Lafora's disease). Onset was in early adult life, and death was at age fifty-four. The initial symptoms were epileptic seizures and progressive dementia, with later occurrence of myoclonus. Lafora bodies were ubiquitous and in neuronal perikarya in many areas. Dust-like granular bodies predominated in the neuropil of cerebral cortex, substantia nigra, and striatum. Abnormal deposits were also found in the myocardium.

Brain↗
PubMed1991

Purification of a nicotinic acetylcholine receptor from rat brain by affinity chromatography directed at the acetylcholine binding site.

We have purified a nicotinic acetylcholine receptor from rat brain by use of an acetylcholine affinity resin commonly employed for the purification of nicotinic acetylcholine receptor from electric tissue. Receptor, specifically eluted with nicotine, bound (-)-[3H]nicotine with a dissociation constant of approximately 21 nM. Binding was inhibited by carbamylcholine but not by alpha-bungarotoxin. Polyacrylamide gel electrophoresis yielded two protein bands, of apparent mol. wts. 80,400 and 52,400. These results provide independent confirmation of the subunit size and composition reported for rat brain nicotinic receptor isolated by immunoaffinity methods and demonstrate a method of purification that can be performed with commercially available reagents.

Acetylcholine↗
PubMed1991

Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up.

Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in "on" time without dyskinesias and a decrease in the severity and duration of "off" time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in "on" time without dyskinesia and a reduction in the severity and duration of "off" time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy.

Adrenal Medulla↗
PubMed1991

Autoradiographic study of iron-binding sites in the rat brain: distribution and relationship to aging.

Specific binding of 59Fe to various brain structures was investigated in rats using nanomolar concentrations of 59FeCl3 and quantitative autoradiography. Saturation studies revealed high affinity binding (kd in the nanomolar range) with binding sites density (Bmax) which varied in different brain regions from 462 fmol per mg tissue in the central thalamic nuclei to over 4 pmol per mg tissue in the cerebral peduncle. Binding was seen in both white and gray matter structures. Bmax values for frontal cortex, dentate gyrus, and substantia nigra were significantly lower in older rats. The distribution of 59Fe binding sites was not consistent with the distribution of brain iron as reported by other investigators. 59Fe binding was reduced significantly in the presence of free radicals. These observations suggest that high affinity binding sites for iron are localized differentially in various brain structures and may play an important role in the translocation and storage of potentially harmful ferric cations in brain. The finding that the capacity of the brain tissue to bind iron diminished with age in discrete brain regions suggests that in the aged animal, the removal of "free" iron from the cellular domain may be impaired in such regions, leading to increased susceptibility to iron-enhanced lipid peroxidation and cell death.

Aging↗
PubMed1990

An autoradiographic study of the uptake and distribution of iron by the brain of the young rat.

Rats aged 15, 28, or 42 days were injected intraperitoneally with iron-59 and were sacrificed at varying intervals. Total acquisition of iron-59 by the brain, when compared to levels of iron-59 in blood sampled 48 h after injection, diminished with increasing age at injection. Cerebral levels of iron-59 in animals injected at age 15 days did not change with postinjection interval despite rapidly decreasing serum levels of iron-59. Thus, iron acquired by the brain early in postnatal development becomes sequestered in that organ. However, autoradiography of the brains of animals injected at age 15 days showed definite changes over time in the anatomic distribution of the isotope. This suggests that mechanisms may exist for the translocation of iron from one area of the brain to another.

Aging↗