Biomedical subjects
Publications and source records attributed to J Palo.
Brains from a prospective study of demented patients were investigated post mortem. Of the 27 patients with clinical diagnosis of vascular dementia, 23 showed multiple cerebral infarcts but senile plaques and neurofibrillary tangles were absent or in insignificant numbers. This gives an accuracy of 85%, a figure higher than previously documented.
Explore the source record for details and available documents.
A neurological outpatient department studied 323 consecutive referrals for suspected dementia: 135 (41.8%) were not demented. Of the patients 12.1% had diffuse cognitive disorder; 10.2% circumscribed memory disorder; 0.9% other circumscribed cognitive disorder, 14.2% psychiatric disorder, and 4.3% were judged to be normal. Of the nondemented, 44.1% had a potentially treatable cause for their cognitive symptoms; in 27.4% it was depression. The total of demented patients was 188 (58.2%): 38.8% had primary degenerative dementia; 37.2% vascular dementia including combined degenerative and vascular dementia; and 23.4% had a specific cause. Patients with specific cause were significantly younger than those with other causes of dementia. A potentially treatable cause was found in 10.7% of all demented patients, the most common being metabolic disorders, meningioma, hydrocephalus, subdural haematoma, and depressive pseudodementia.
A prospective series of consecutively admitted patients with Alzheimer's disease (AD) (n = 68), multi-infarct dementia (MID) (n = 79) and probable vascular dementia (PVD) (n = 46) were studied by CT of the head. In MID 88.6% and in PVD 41.3% of the patients had at least one brain infarct on CT, but only one patient (1.5%) with AD. White matter low attenuation (WMLA) also differentiated MID and PVD from AD, especially among patients aged 75 years or less, and with mild or moderate dementia. In all types, brain atrophy on CT had a positive correlation with the degree of dementia. Infarcts and WMLA on CT, but not brain atrophy seem to be of differential diagnostic value between vascular and degenerative dementia.
Serum concentrations of IgG, IgA, IgM, haptoglobin, transferrin, prealbumin and albumin quantitated nephelometrically in 22 patients with Alzheimer's disease (AD), 29 patients with multi-infarct dementia (MID) and their age-matched controls were normal. Cerebrospinal fluid (CSF) albumin and CSF/serum ratio for albumin were higher in AD and MID patients compared to controls, but no significant differences were found between AD and MID. Patients with MID had elevated CSF IgG, IgA, IgM and prealbumin levels compared to controls and to AD. An increased CSF IgG index was found in 5 MID patients but none of the AD patients. Thus, the blood-brain barrier permeability is often increased in MID as well as in AD. There is no increased intrathecal IgG synthesis in AD but it may occur in MID.
Long-chain polyisoprenol alcohol (dolichols) levels are significantly increased in the urinary sediment of patients with infantile, late-infantile, and juvenile forms of neuronal ceroid-lipofuscinosis (NCL). The values in obligate heterozygotes for these diseases are similar to those in patients with other neurological diseases and in healthy controls. Antioxidant treatment of patients with juvenile NCL has no effect on dolichol values. The rate of false-negative results is 13.9% in infantile, 7.5% in late-infantile, and 15.0% in juvenile NCL. False-positive results were found in 8.2 to 14.3% of patients with other neurological diseases and in 15.4% of healthy controls. The test is of considerable value in the diagnosis of NCL and in decisions on whether to perform a biopsy. It is not useful in the screening of random samples, however.
In view of the hypothesis that a biochemical abnormality in the childhood forms of neuronal ceroid-lipofuscinosis may lie in the utilization of dolichols in glycoprotein synthesis, we analyzed the oligosaccharide structures of brain glycoproteins in infantile neuronal ceroid-lipofuscinosis (INCL). Lectin affinity chromatography of purified glycopeptides and of oligosaccharides prepared by hydrazinolysis showed an increase in high mannose-type glycopeptides and a decrease in tri- and tetra-antennary glycopeptides in INCL brain when compared with control brain. These changes were more pronounced in the storage cytosomes than in whole brain. Methylation analysis of the isolated glycopeptide fractions did not reveal differences in substitution patterns of the individual sugar residues between INCL and control brain. In INCL the core disaccharide of the O-glycosidically-linked oligosaccharides was sialylated to a higher degree than in control brain indicating that the structural changes were not confined only to N-glycosidically-linked carbohydrate chains. The observed structural changes in the carbohydrate chains of brain glycopeptides in INCL could be explained by a defect in the biosynthesis of glycoproteins. Alternatively, the changes may reflect the increased glial cell population in the degenerating brain. In fact, the elution profiles in lectin chromatography of oligosaccharides prepared from cultured rat glioma cells resembled those from INCL brain.
A random sample of 182 elderly community residents and 211 demented patients were studied using the D-Test Battery based on the Luria's neuropsychological investigation method. A steady but selective cognitive impairment was observed with increasing age in normal healthy subjects. The most sensitive areas of cognition to the effects of normal aging were mnestic and conceptual functions, as well as arithmetical skills. The age-related changes could be clearly differentiated from the changes found in patients with mild degree of dementia. The test also differentiated patients with mild, moderate and severe dementia from each other on the basis of their social competence. It failed to demonstrate specific patterns of impairment and to clearly differentiate between patients with Alzheimer's disease and vascular dementia who had the same degree of cognitive decline. Further qualitative analyses are needed to improve the sensitivity and specificity of the test.
The concentrations of serum amyloid A (SAA) protein, albumin and prealbumin were measured in 22 patients with Alzheimer's disease (AD), in 21 demented patients with Down's syndrome (DS), and in age-matched control subjects for both groups in a 2-year follow-up study. The concentration of SAA was initially elevated in 9 of 22 (41%) patients with AD and in 8 of 21 (38%) patients with DS. After 2-years, 10 of 12 (83%) AD patients and 11 of 14 (79%) DS patients had elevated SAA levels but with fluctuation of the values. None of the controls revealed increase in the SAA level. The concentration of SAA did not correlate with the duration of AD or AD-like process although the highest values were found in cachectic AD patients confined to bed. Although neoplasm or infection were not diagnosed, the presence of occult neoplasm or subclinical infection as a cause of SAA elevation, especially in the DS group susceptible to infection, could not be excluded. Moreover, the fluctuation of SAA values in DS seems likely to be associated with an infection. Albumin and prealbumin levels were decreased in both AD and DS; the prealbumin levels in AD was lower than that in DS.
Antibodies to cytomegalovirus (CMV) were determined in the serum and cerebrospinal fluid (CSF) by complement-fixing (CF), enzyme immunoassay (EIA), and enhanced virus neutralization test (EVNT), in acute unmedicated schizophrenic patients and neurological controls. An elevated level of CF antibody was observed in three serum specimens from the schizophrenic patients and in one control specimen. No CF antibody was present in the CSF samples of the two patient groups tested. By EIA none of the serum or CSF specimens was positive for IgM antibody to CMV. By EVNT, 17% of the schizophrenic patients exhibited a CSF/serum ratio greater than 2 SD, whereas the corresponding figure for the control group was 4% (P greater than 0.05). The role of CMV in the etiopathogenesis of schizophrenia is discussed in the light of the present and previous negative findings.
Monozygotic twin sisters were afflicted by a chronic progressive neurological disease characterized by slurred speech, nystagmus and oculogyral spasms as well as further extrapyramidal and lower motor neuron abnormalities. At autopsy severe loss of nigral and craniospinal motor neurons was noted. In the nuclei of most nerve cell types of the central and peripheral nervous system, roundish inclusion bodies of 3 to 10 microns in diameter were found. Ocular pathology revealed the presence of identical inclusion bodies in the ganglion cells and ganglion cell loss in the posterior retina. Retinal astrocytosis and loss of myelinated axons of the optic nerve were interpreted as reactive features. No inclusions were found in the retinal pigment epithelium. Careful neuro-ophthalmological studies of the first-degree relatives revealed low b-wave of the ERG with other slight aberrations. These were assumed to represent either a carrier or a subclinical state of this presumably inherited disorder.
Two thousand consecutive patients aged 55 years and older admitted to a department of medicine in a large university hospital were examined for the presence of dementia. The occurrence of moderate and severe dementia was 9.1% for all age groups. It increased from 0.8% in the age group from 55 to 64 years to 31.2% in patients aged 85 years and older. Of the demented patients, 41.4% were delirious at admission, and 24.9% of all delirious patients were demented. Patients with vascular dementia constituted 72.4%, those with primary degenerative dementia 23.0%, and those with specific causes 4.6% of all demented patients. The mean hospitalization time for demented patients was significantly longer, and they needed significantly more daily nursing care, when compared with nondemented patients.
Explore the source record for details and available documents.
A 26-yr-old female with increased urinary excretion of free N-acetylneuraminic acid is described. Her early history was normal but she had difficulties at school and developed epilepsy at 14. She is mildly retarded, has slight changes in the spine, but no hepato- or splenomegaly. Cerebrospinal fluid leucocytes and IgG are elevated. Liver and skin biopsies disclosed no morphological abnormality. The daily excretion of free N-acetylneuraminic acid is ca. 0.5 g, intermediate to that found in other known types of sialuria. The clinical and morphological findings are also different suggesting a novel type of sialuria.
Material extracted and partially purified from human cerebrospinal fluid (CSF) is capable of: a, inhibiting [3H]ouabain binding to rat brain synaptosomes; b, inhibiting the activity of purified pig kidney Na+,K+-ATPase; and c, inhibiting ouabain sensitive induced 86Rb influx to tissue cultured fibroblasts. These results demonstrate the existence of an 'ouabain like' compound (OLC) in human CSF, and are consistent with the hypothesis of the function of this compound as a neuromodulator.
Extremely severe gliosis develops at the end stage of infantile neuronal ceroid-lipofuscinosis (INCL), a fatal encephalopathy characterized by accumulation of autofluorescent storage material in the brain and other tissues followed by a terminal subtotal neuronal and myelin loss. A major fraction of highly enriched intermediate filaments was obtained with a density gradient centrifugation method from INCL brain tissue, whereas the storage material represented only a minor fraction. SDS-polyacrylamide gel electrophoresis of the filament fraction showed a major protein with molecular weight of 51 kD and three to four polypeptides of 40-48 kD identified as glial fibrillary acidic protein (GFAP) and its degradation products by the immunoblotting technique with monoclonal antibodies against GFAP. Immunization experiments with the isolated INCL glial filament fraction produced antibodies reacting only with GFAP but not with other types of intermediate filament proteins, furthermore indicating a high content of GFAP in the isolated fraction. No significant amounts of vimentin or other types of intermediate filament proteins could be detected. These results document the extremely high content of glial filaments at the terminal stage of INCL and suggest that INCL brain may serve as a good human model for studies on the composition of glial filaments in vivo and on the pathogenesis of gliosis.