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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

594 records · Page 33Linked to original sources

Neuroglia in the inferior olivary nucleus during normal aging and Alzheimer's disease.

It is likely that neuronal loss occurs in certain brain regions in Alzheimer's Disease (AD) without any neurofibrillary pathology. In the human principle inferior olivary nucleus (PO), we have shown that neuronal loss is about 34% (Lasn et al. Journal of Alzheimer Disease, 2001; 3: 159-168), but the fate of the neuroglial cells is unknown. Since the unique network of neurons and neuroglial cells and their cohabitation are essential for normal functioning of CNS, we designed a study to estimate the total number of oligodendrocytes and astrocytes in normally aged and AD brains. The study is based on 10 control and 11 AD post-mortem human brains. An unbiased stereological fractionator method was used. We found significant oligodendroglial cell loss (46%) in AD as compared to control brains, while the total number of astrocytes showed a tendency to decrease. It is likely that the ratio of oligodendroglial cells to neurons remains unchanged even in degenerative states, indicating that oligodendroglial cells parallel neuronal loss. Astroglial cells did not increase in total number, but the ratio to neurons was significantly increased due to the neuronal loss. Using a novel unbiased quantitative method, we were able to describe significant oligodendroglial loss in the PO but the pathogenic mechanism behind remains unknown.

Adolescent↗

Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease.

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer's disease. We have treated 3 patients with Alzheimer's disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.

Aged↗

Decreased plasma insulin-like growth factor-I level in familial Alzheimer's disease patients carrying the Swedish APP 670/671 mutation.

The plasma insulin-like growth factor I (IGF-I) level was determined in family members carrying the Swedish amyloid precursor protein (APP) 670/671 mutation with or without Alzheimer's disease (AD) and in age-matched controls from the same family. Plasma growth hormone (GH) and prolactin (PRL) levels were also determined. Measurement of the plasma IGF-I level by radioimmunoassay revealed a significant reduction only in the family members with AD compared to age-matched controls. However, there was no significant difference in the levels of GH and PRL between the mutation carriers with or without AD and their respective age-matched controls. These findings indicate that the mechanism(s) regulating GH and PRL were preserved and those regulating IGF-I levels might be affected in AD patients with the Swedish APP 670/671 mutation. CopyrightCopyright 1999S.KargerAG, Basel

Aged↗

The Gottfries-Bråne-Steen scale: validity, reliability and application in anti-dementia drug trials.

Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Bråne-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.

Activities of Daily Living↗

White matter lesions impair initiation of FAS flow.

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137-143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer's disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.

Aged↗

Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population.

In a cohort study, 1,301 subjects free of dementia at baseline in the Kungsholmen Project were followed up to 6 years. We studied the association between use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), incidence of Alzheimer's disease (AD) and overall dementia, and the influence of the apolipoprotein E epsilon4 allele. In stratified analyses, a relative risk (RR) of 1.80 (95% CI 1.14-2.83) for AD was seen, in the apoE epsilon4-negative group using aspirin. This implicates a possible different mechanism of developing AD in this group. We also found a possible protective effect of NSAIDs against AD, since no one who used NSAIDs for around 3 years had developed AD 3 years later. One user developed vascular dementia, and a low point value of risk was seen, however, not significant (RR 0.23; 95% CI 0.03-1.68). This could be due to the small samples in our study, or to comorbidity contributing to the development of dementia in this elderly population.

Aged↗

Intact brain serotonin system in vascular dementia.

Pre- and postsynaptic elements of the 5-hydroxytryptamine (5-HT, serotonin) system were studied in a control group and in patients with vascular dementia (VAD). The 5-HT uptake site was used as a presynaptic marker for 5-HT terminals and 5-HT1A and 5HT2 receptors were used as postsynaptic markers. The binding sites were quantified with radioligand binding techniques, where the radioligands used were [3H]paroxetine, [3H]8-OH-DPAT and [3H]ketanserin, respectively. The presynaptic uptake site was studied in frontal and temporal cortices and caudate nucleus. 5-HT1A and 5-HT2 receptors were studied only in frontal and temporal cortices. There were no differences between control and VAD groups in any of the regions investigated with respect to the number of binding sites (Bmax) and binding affinity (Kd). This indicates that both pre- and postsynaptic parts of the 5-HT system are intact in these brain areas in VAD.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment.

In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer's disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbance, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.

Aged↗

Visuospatial performance in very old demented persons: an individual difference analysis.

This study examines selected demographic, psychometric, and biological measures as predictors of visuospatial performance in a sample of 98 persons with mild to moderate dementia. Visuospatial performance was measured using standardized neuropsychology instruments, namely: Poppelreuter's figures, the clock test, and block design. Although multiple measures were initially correlated with performance on the selected visuospatial tests, the Mini-Mental State Examination was the exclusive predictor of Poppelreuter's figures and the clock test scores. For block design, years of education also contributed to the prediction model, but only among mildly demented persons. These results suggest that disease severity plays a dominant role in the prediction of visuospatial performance in dementia, particularly in more advanced stages of the disease. The differential role of education in predicting block design performance in mild vs. moderate dementia was also highlighted.

Aged↗

Variation in psychiatric and behavioural symptoms at different stages of dementia: data from physicians' examinations and informants' reports.

An investigation was carried out of psychiatric and behavioural symptoms in non-demented and demented subjects derived from a population study of the very elderly. Information on psychiatric and behavioural symptoms came from two independent sources: a physician's examination and an interview with an informant. The symptoms were grouped into clusters using principal-components analysis. Little agreement was found between the two sources of information on symptoms of anxiety, depression and psychosis. However, there was agreement about an increase in inactivity symptoms as the severity of dementia increased.

Aged↗

Brain and plasma proteins in spinal fluid as markers for brain damage and severity of stroke.

Forty well-defined acute stroke patients were investigated for some cerebro-spinal fluid (CSF) markers of cerebral damage. Myelin-basic protein (MBP), tau-fraction, albumin, IgG and transferrin were analyzed on two early occasions after onset of clinical symptoms. Patients with transitory ischaemic attack (TIA) had normal values for MBP both at first and second lumbar puncture. Patients with cerebral infarction and haemorrhage had mean MBP concentrations higher than normal at both lumbar punctures. In cerebral infarction there was a significant increase in MBP from the first to the second lumbar puncture. Patients with intracerebral haemorrhage showed the highest mean MBP values and MBP was markedly elevated already at the first lumbar puncture, suggesting different mechanisms of destruction of nervous tissue in cerebral infarction and bleeding. The amount of MBP was also significantly correlated to the visibility of the cerebral lesion at CT-scan and to the short-term outcome of the patients. The tau-fraction, indicating damage to grey matter, was higher than normal in the majority of patients with cerebral infarction and TIA. The concentration of MBP increases with the extent of brain lesion and a high value indicates a poor short-term prognosis for the patient. This study shows that the brain specific MBP in CSF is a useful marker of cerebral damage in acute cerebrovascular disease.

Acute Disease↗

Survival after haemorrhage from the brachiocephalic truncus following tracheostomy.

A patient with two massive haemorrhages from the brachiocephalic truncus after tracheostomy is reported. An analysis of 6 previously reported long-term survivors following this complication shows that the initial care in controlling the haemorrhage is of major importance. The operation method of choice is permanent division of the brachiocephalic truncus. Transitory or no neurological postoperative complications were found.

Animals↗

Aspergillosis of the maxillary sinus. Clinical and histopathological features of 4 cases and a review of the literature.

Four patients with aspergillus maxillary sinusitis are reported and a review of the literature on aspergillus paranasal sinusitis during the last 10 years is presented. The patients had symptoms and X-ray findings similar to a chronic bacterial sinusitis. One patient had been operated upon 6 years previously due to a chronic sinusitis and 3 of the patients had been treated with broad-spectrum antibiotic drugs. Caldwell-Luc operations were performed, also to exclude malignant tumours. The aspergillus etiology of the sinuitis was discovered in routine stained sections by histo-pathological examination of the sinus mucosae. No recurrence of the fungus infection occurred after the Caldwell-Luc operation, which was valuable for the correct diagnosis as well as being the best suited therapy.

Aged↗

The healing pattern of experimental pars flaccida perforations.

The aim of this investigation was to ascertain how a traumatic perforation of the pars flaccida heals and whether this could explain the way in which the retraction pocket develops. In rats, traumatic pars flaccida perforations were performed on both ears and the healing pattern was registered after various intervals. The perforations healed in 7-10 days, forming in the first instance an indrawing of the pars flaccida and after 12-14 days an adhesive retraction, i.e., ther pars flaccida adhered to the neck of malleus. The retraction pocket was filled with wax, keratin and detritus. At the base of the retraction, epithelial inclusions could be found, which could explain why these retractions were not self-cleaning.

Animals↗

Repair of experimental tympanic membrane perforations.

In this investigation the healing pattern of experimental central and marginal pars tensa perforations in cats and rats was studied by using light and scanning electronmicroscopic techniques. The perforations were closed by hyperplastic squamous epithelium exhibiting a marked keratin production. This keratin formed a membranous structure which primarily appeared to close the perforation. No ingrowth of squamous epithelium into the middle ear cavity could be detected. Generally speaking, the perforations had closed within 9-11 days in rats and within 12-14 days in cats.

Animals↗

Prevention of vascular dementia.

Stroke is an important public health problem worldwide. Those at high risk of stroke may be at high risk of cognitive impairment and dementia after stroke. Modifiable cardiovascular risk factors in midlife including hypertension, alcohol use, cigarette smoking, and certain dietary factors may be important targets for prevention of vascular causes of cognitive impairment. These same types of factors may also be associated with Alzheimer disease. Better control of cardiovascular disease risk factors might lead to delay or prevention of vascular dementia and Alzheimer disease.

Alcohol Drinking↗

Protein III, a neuron-specific phosphoprotein: variant forms found in human brain.

Protein III is a neuron-specific phosphoprotein which consists of two polypeptides, IIIa (Mr 74 kD) and IIIb (Mr 55 kD). This phosphoprotein has previously been shown to be associated with synaptic vesicles. In the present investigation, we have examined Protein III in human brain tissue. In contrast to observations in rat brain, where only one form of Protein IIIb (Mr 55 kD) has been found, in human brain tissue three variants of Protein IIIb, designated Protein IIIb1 (Mr 55 kD), Protein IIIb2 (Mr 57 kD) and Protein IIIb3 (Mr 59 kD), were observed by both biochemical and immunochemical assays. Protein IIIa from human brain also exhibited three variants in electrophoretic mobility. Peptide maps of Proteins IIIa and IIIb revealed that the differences in electrophoretic mobility of the variants of these proteins were preserved in variants (Mr 18kD, Mr20kD, and Mr22kD) of a smaller peptide fragment. These variant forms of Protein III were studied in brains from individuals without any history of neurological or psychiatric illness, as well as from individuals who had suffered from one of several types of neuropathological conditions, such as chronic alcoholism, Alzheimer's disease, multi-infarct dementia, and Parkinson's disease. Some differences were observed in the distribution of variants among the various clinical categories.

Adult↗