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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 415 records · Page 23Linked to original sources

Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?

In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10(-4) M and physostigmine 10(-4) M significantly increased the release of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10(-6) M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10(-5) M significantly increased the 3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.

Acetylcholine↗

Determinants of long-term mortality after stroke.

Risk factors of death for a population of 409 patients with well-defined cerebrovascular disease (patients with subarachnoidal hemorrhage excluded) admitted to the Stroke Unit were studied with the aid of the life table technique, log rank test, and multivariate analysis with BMDP's program for regression on the survival curves with Cox's proportional hazard model. The estimated proportion of survivors was 77% after three months, 69% after one year, and 32% after five years. Patients with intracerebral hemorrhage and embolic cerebral infarction had the worst outcome. Impaired consciousness on admission was the most important risk factor of death followed by high age, previous cardiac failure, diabetes mellitus and male sex.

Adult↗

Autopsy-verified causes of death after stroke.

In a population-based sample of 409 stroke patients, autopsy was performed in 82 of the 95 patients who died during the first three months and in 61 of the 128 patients dying thereafter. The dominant causes of death, as verified by autopsy, were cerebrovascular disease in the first week (90%), pulmonary embolism in the second to fourth week (30%), bronchopneumonia during the second and third months (27%) and cardiac disease, mainly myocardial infarction, later than three months after the stroke (37%). Death was attributed to causes other than the brain lesion in 59% of the patients with ischemic and in 24% of the patients with hemorrhagic stroke (p less than 0.01). Age and sex had little influence on the distribution of causes of death. Fatal pulmonary embolism and bronchopneumonia surprisingly often occurred in ambulatory patients. An intracardiac thrombus was present in 20% of deceased patients with atrial fibrillation, and in 17% of cases with a history of myocardial infarction. When attempts are made to reduce mortality (and morbidity) after stroke, there would seem to be a considerable potential for prevention and early treatment of complications, such as pulmonary embolism, bronchopneumonia and cardiac disorders.

Adult↗

A model for the assessment of eating problems in patients with Parkinson's disease.

A model for the assessment of eating problems in patients with Parkinson's disease was constructed on the basis of literature about eating and Parkinson's disease. The model is based on the World Health Organization's classification of disabilities and handicaps and on the Erikson theory of 'eight stages of man'.

Persons with Disabilities↗

Linkage of G8 (D4S10) in two Swedish families with Huntington's disease.

Two Swedish families with Huntington's disease (HD) have been investigated for linkage with G8 (D4S10). In one family from northern Sweden (Family 1) 48 family members were examined, and in another family from the southwestern part of Sweden (Family 2) 14 family members were examined. The lod scores were 1.531 for Family 1 and 2.057 for Family 2, and the combined lod score was 3.59. The HD gene was segregating with the haplotype C in Family 1 and with haplotype A in Family 2. The predictive value of the test was obvious. Before the testing with the G8 probe, 84.2% of the family members in Family 1 had a theoretical risk of 25% or 50% of having the HD gene. After the testing with the G8 probe, only 23.7% of the family members remained at the same risk, and it could also be certified that 63.2% had no or little risk of having the HD gene. Only one asymptomatic person was predicted to have HD.

Female↗

Nutritional status and dietary intake in institutionalized patients with Alzheimer's disease and multiinfarct dementia.

Nutritional status, dietary intake, weight change, and mortality were studied in a sample of severely demented, institutionalized patients. Dietary intake was registered during five days in two periods, five weeks apart. A weighing method was used. Nutritional status was assessed by anthropometric measurements (weight for height index, triceps skinfold thickness, arm muscle circumference) and determination of circulating proteins (albumin, transferrin, and prealbumin). Energy and/or protein malnutrition was found in 50% of the patients. The mean dietary intake was sufficient according to energy (2059 kcal/day), proteins, vitamins, and minerals. A comparison of patients with or without malnutrition showed no differences in dietary intake, diagnoses, age, length of hospital stay, or duration of illness. However, malnourished patients had had four times as many infectious periods treated by antibiotics as patients with no malnutrition. Thirty-nine of 44 patients lost weight during their hospital stay. There was no correlation between loss of weight, length of hospital stay, or duration of illness.

Aged↗

Increased monoamine metabolite concentrations and cholinesterase activities in cerebrospinal fluid of patients with acute stroke.

Twenty-one patients with acute brain infarction, 8 with transient ischemic attack and 20 controls were investigated for lumbar cerebrospinal fluid (CSF) monoamine metabolites and cholinesterases. The diseased patients were lumbar punctured on 2 occasions, mean Days 1 (0-3) and 5 (3-9) after debut of symptoms. Monoamine concentrations were determined by reverse phase liquid chromatography with electrochemical detection and the cholinergic enzymes were measured photometrically. Increased concentrations of 3-methoxytyramine (3-MT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HI-AA) and increased activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in lumbar cerebrospinal fluid was found in patients with acute brain infarction when compared to control values, while the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were not altered. No change of any neurotransmitter metabolite concentration/enzyme activity were found between Day 1 and Day 5 in the diseased patients. These data suggest an increased release of these neurotransmitter markers from necrotic brain areas into the cerebrospinal fluid and/or altered barriers between blood, brain and CSF and/or a dysfunction of the arachnoid villi to clear substances from the CSF. We therefore concluded that CSF neurotransmitters may be useful as specific brain markers in acute stroke.

Acute Disease↗

Iontophoretic study of adrenergic and cholinergic skin vessel reactivity in normal ageing and Alzheimer's disease.

Iontophoresis was used to evaluate the peripheral reactivity of phenylephrine (alpha 1-agonist), isoproterenol (beta-agonist) and metacholine (cholinergic agonist) in patients with Alzheimer's disease (AD). The cutaneous responses--erythema and blanching--were visually recorded. Healthy personnel, medical students and patients with various dermatoses served as controls. A reduced response towards the adrenergic agonists was seen in AD. The reduced sensitivity was highly significant for the beta-agonist isoproterenol (p less than 0.001), in contradistinction the metacholine response did not differ between AD and age-matched controls. Furthermore, increasing age did not seem to significantly influence the cutaneous responses in mentally healthy controls. Thus, a reduced peripheral adrenergic reactivity was observed in the patients suffering from AD.

Adolescent↗

Attitudes of health care personnel toward demented patients.

Health care personnel (n = 724) working in psychogeriatric care, somatic and psychiatric long-term care, somatic and psychiatric general care and in homes for the aged, were interviewed by means of questionnaires evaluating attitudes and intentions regarding work with demented patients and education in their care. The overall attitude towards demented patients was positive. The largest numbers of personnel with positive attitudes were found in psychogeriatric care and somatic long-term care and the lowest in general medical and psychiatric care. The figure for positive attitudes in relation to education showed a similar figure for all categories. Given a free choice only 4% of the respondents had the intention of working solely with demented patients. A majority of the respondents reported that their knowledge of the care of demented patients came from clinical work. There is a strong need for further education.

Adolescent↗

Patterns of memory performance in young-old and old-old adults: a selective review.

Three experiments were discussed as a means of bridging the gap between biological and psychological data on aging and memory. Memory performances of young-old (73 year-old) and old-old (82 year-old) subjects were compared. The common denominator of these experiments was that contextual or cognitive support had been provided at study and/or test. The rationale behind discussing these experiments in the present context was that subjects should be able to use this support to focus attention on the critical aspects of the to-be-remembered information; thereby the subjects should be able to compensate for neurological degeneration pertinent to attentional difficulties. The nature of the differences between young-old and old-old subjects was found to vary among tasks. Study 1 demonstrated qualitative differences between young-old and old-old subjects, whereas Studies 2 and 3 demonstrated the differences to be merely quantitative in nature. Implications for memory training programs for the elderly were discussed.

Adult↗

Postoperative confusion after anesthesia in elderly patients with femoral neck fractures.

Fifty-seven patients, all over the age of 64, with femoral neck fracture were randomized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion. All patients were lucid on admission. Using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as criteria for confusion, we found that 44% of the patients developed confusion that correlated closely to a history of mental depression (P less than 0.01) and to the use of drugs with anticholinergic effect (P less than 0.005). There was no difference in the incidence of confusion between the two anesthetic groups. In patients given halothane, however, early postoperative hypoxemia was associated with confusion (P less than 0.05). Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times. It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique.

Aged↗

Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains.

Nicotinic cholinergic receptors were measured in human frontal cortex using [3H]nicotine and [3H]acetylcholine (in the presence of atropine) as receptor ligands. A parallel marked reduction in number of [3H]nicotine (52%; P less than 0.01) and [3H]acetylcholine (-55%; P less than 0.05) binding was found in the frontal cortex of Alzheimer brains (AD/SDAT) when compared to age-matched control brains. As a comparison the number of muscarinic receptors was quantified using [3H]quinuclidinyl benzilate and found to be significantly increased (+23%; less than 0.01) in AD/SDAT compared to controls.

Aged↗

Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type.

The relative proportion of super-high, high and low affinity agonist binding sites was measured in the hippocampus from individuals with dementia of the Alzheimer type (AD/SDAT), mixed (AD-MID) type and controls, using labelled quinuclidinyl benzilate ([3H]QNB) competing with unlabelled carbachol. A significant reduced number of [3H]QNB binding sites was obtained in dementia groups. A significant decrease in the proportion of super-high affinity agonist (V1) binding sites was found in the AD-MID group compared to controls while no change was found in the AD/SDAT group. The affinity constant (K1) for the V1 site was also significantly lower in the AD-MID group compared to controls.

Aged↗

Defective brain microtubule assembly in Alzheimer's disease.

Brains obtained within 2-4 hours post mortem and histopathologically confirmed for Alzheimer's disease and non-Alzheimer brains from age-matched controls were examined for in-vitro assembly of microtubules and neurofilaments. Microtubule assembly was observed only in control but not in Alzheimer brains, and neurofilaments were obtained from both types of brain. The microtubule-associated protein tau, which stimulates assembly of microtubules from tubulin, was abnormally phosphorylated in Alzheimer but not in control brain microtubule preparations. Alzheimer brains did not show the presence of any inhibitor of microtubule assembly or any abnormality of tubulin. DEAE-dextran, a polycation which mimics tau in stimulating microtubule assembly, induced the assembly of microtubules in Alzheimer brain. Tubulin from both normal and Alzheimer brains was labelled on western blots by a monoclonal antibody to the tyrosinylated carboxy-terminal epitope of alpha tubulin. These studies suggest that in Alzheimer's disease tubulin can be assembled into brain microtubules, but the process is defective, probably because of abnormal phosphorylation of tau. This post-translational alteration of tau might be the cause of the neurofibrillary abnormality in Alzheimer's disease.

Aged↗

Physostigmine restores 3H-acetylcholine efflux from Alzheimer brain slices to normal level.

A technique was developed, which made it possible to study the in vitro release of 3H-acetylcholine (3H-ACh) from human post mortem brain tissue, collected with short post-mortem delay (2,5-22 hours), both from controls and patients with Alzheimer's disease (AD/SDAT). The tritium (3H) release was investigated during potassium stimulation, and AD/SDAT cortical slices were found to release a decreased amount of 3H compared to control brain slices. Physostigmine, 10(-5) and 10(-4) M, has no significant effect on the release of 3H from control slices, while physostigmine 10(-4) M increased the evoked release from AD/SDAT brain slices over threefold, nearly to the control level.

Acetylcholine↗