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Biomedical subjects

C G Gottfries

Publications and source records attributed to C G Gottfries.

At least 145 records · Page 8Linked to original sources

Alzheimer's disease.

Alzheimer's disease and senile dementia are considered primary degenerative disorders of the brain. The delimitation of the two disorders is their onset: whether it is before or after the age of 65 years. As the neuropathological findings in the two disorders are similar they sometimes are sampled together. Biochemical investigations have shown extensive and severe disturbances of neurotransmitters in the brain of patients with Alzheimer's disease and senile dementia. Although the acetylcholinergic system is severely damaged and has been given special etiological importance, it seems that also the monoaminergic, the GABA-ergic and the neuropeptidergic systems are deranged. The extensive damage to the neurotransmitter systems indicates an etiology beyond the transmitter level. It is natural to assume that the disturbed neurotransmitters have pathogenic importance for the disorder. Pharmacological treatment trials have been performed in which the failing systems are substituted. Hitherto, however, these trials have not been as successful as expected.

Aged↗

Changes in dopamine receptor sensitivity in humans after heavy alcohol intake.

Dopamine (DA) sensitivity, assessed through maximal growth hormone (GH) response to stimulation by apomorphine (APO) (0.18-0.24 mg iv) was studied in 16 chronic alcoholics newly admitted after a period of heavy alcohol intake. Repeated hormonal tests were thereafter performed during a 2-month period under strictly controlled conditions to avoid relapse into alcohol consumption. Eight healthy volunteers with alcohol consumption slightly less than that of the general population were used as controls. It was found that DA sensitivity in the early abstinence phase was higher than later in the 2-month recovery period but not significantly different from control values. The relatively higher DA sensitivity in the early abstinence phase might be responsible for a lower threshold for psychotic symptoms and neuroleptic-induced extrapyramidal side effects. The results of this study give further evidence of a prolonged recovery phase after heavy alcohol intake.

Adult↗

Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment.

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them. The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD. Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholinesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system. Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis. In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides. The biochemical changes can be given pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Superoxide dismutase isoenzymes in normal brains and in brains from patients with dementia of Alzheimer type.

CuZn superoxide dismutase and Mn superoxide dismutase were analysed in hypothalamus, nucleus caudatus, hippocampus and cortex gyrus cinguli from 14 patients with dementia of Alzheimer type and from 16 controls. Ample amounts of both enzymes were demonstrated in the brains and there was little difference between the various parts of the brain. There were only small differences in the enzymic activities between the two groups indicating that deficiencies of these enzymes are not a very likely cause of brain degeneration in dementias of Alzheimer type.

Age Factors↗

Alaproclate: a pharmacokinetic and biochemical study in patients with dementia of Alzheimer type.

Alaproclate, a specific inhibitor of neuronal serotonin re-uptake, was given to 12 patients with dementia of Alzheimer type. The drug was rapidly absorbed and an elimination half-life of 7.1 +/- 0.9 h (+/- SD, n = 8) was calculated. Plasma protein binding for alaproclate was 82 +/- 1%. Two weeks of repeated administration produced plasma concentrations of alaproclate similar to those predicted from a single dose. The pharmacological effect of the drug was demonstrated by an inhibition of serotonin uptake in the patients' platelets and a reduction of the serotonin concentration in blood. Global rating of clinical efficacy showed a positive effect of alaproclate in five of the patients, mainly regarding emotional functions.

Aged↗

The activity of monoamine oxidase -A and -B in brains from chronic alcoholics.

The activity of monoamine oxidase--A was found to be lower in homogenates of hypothalamus and caudate nucleus, but not in cortex of the gyrus cinguli and hippocampus, from chronic alcoholics with respect to homogenates from autopsy cases without histories of alcohol abuse. The activity of monoamine oxidase--B was also lower in the alcoholics, but this could be due to the selective effect of age upon this enzyme form, since the alcoholics were younger than controls. No difference was found for either monoamine oxidase -A or -B activities in brain homogenates from an alcohol preferring (AA) strain of rats, with respect to those from a water preferring (ANA) strain.

Aged↗

Biochemical changes in dementia disorders of Alzheimer type (AD/SDAT).

In postmortem investigations of patients with dementia of Alzheimer type (AD/SDAT) (n = 14) the brain weight was significantly reduced when compared to controls (n = 16). In four AD/SDAT-brain parts investigated the concentrations of 5-hydroxy-tryptamine and noradrenaline were significantly reduced while 3-methoxy-4-hydroxyphenylglycol was significantly increased. In the caudate nucleus of the AD/SDAT-brains the concentrations of dopamine and homovanillic acid were significantly reduced. The activity of monoamine oxidase B was increased suggesting a proliferation of extra neuronal tissue in the AD/SDAT-brains. The activity of choline acetyl transferase was reduced in the four brain parts investigated, showing a general reduction in the acetylcholine system in the AD/SDAT-brains. The ganglioside concentration was significantly reduced suggesting a reduced density of nerve endings in the demented brains. The AD/SDAT-group was according to rating scales severely demented. Patients with an early onset of the dementia disease were more severely intellectually reduced and had more pronounced biochemical disturbances than those with a late onset of the dementia.

Aged↗

Zimeldine in the treatment of depression in the elderly.

Epidemiological data indicate that the incidence of classical melancholia is lower among the elderly; however, light, atypical or secondary depressions appear to become more common during old age. Biochemical changes that occur with age or in association with dementia, may increase vulnerability to affective disorders. Preliminary studies show that zimeldine is an effective antidepressant with low cardiotoxicity and few anticholinergic side-effects, and it appears that the drug is well tolerated by the elderly. Drug regimens need to be carefully tailored to the elderly patient's requirements, however, as first-pass metabolism is reduced in some patients. An objective test to differentiate dementia from depression would be extremely valuable. Unfortunately, no such test has yet been found. The dexamethasone suppression test, for example, has proved to be unreliable in this context.

Aged↗

Dexamethasone suppression test and serum prolactin in dementia disorders.

The dexamethasone suppression test (DST) was performed on 21 patients with dementia of the Alzheimer type (DAT), 11 patients with multi-infarct dementia (MI) and 14 healthy controls. Twelve of the DAT patients and eight of the MI patients showed abnormal lack of suppression, compared with just one member of the control group. Abnormal DST was related to dementia as such and not to age or depression, or to levels of CSF monoamine metabolites. Basal serum prolactin concentrations were not increased.

Aged↗

A new rating scale for dementia syndromes.

A new scale, the GBS-scale, is constructed for rating dementia syndromes. The scale is divided into four subscales measuring motor, intellectual and emotional functions and different symptoms characteristic for dementia. The scale can be used by physicians, psychologists and registered nurses. The reliability of the scale is tested by rating 100 patients in somatic and psychogeriatric long-term care. The raters worked independently of each other and were recommended to confer with the staff about the status of the patient. The agreement between the raters was good. The validity of the scale was tested by comparing it with another geriatric rating scale. High correlations between the two scales were seen and indicated that the new scale measures dementia syndromes. The new scale measures degree of dementia and profiles of dementia syndromes. It is constructed in such a way that it can measure changes in dementia symptoms over a certain amount of time. Thus, it can be used in evaluating effect of treatment. It is not, however, meant to be a diagnostic scale.

Aged↗

Studies on duration of a late recovery period after chronic abuse of ethanol. A cross-sectional study of biochemical and psychiatric indicators.

A cross-sectional study on patients with different abstinence time was performed to describe long-time biochemical and psychiatric changes due to withdrawal from heavy alcohol abuse. Physical, neurological, psychiatric and biochemical parameters were measured in 70 patients with a withdrawal period ranging from 2-90 days. The various parameters changed over time in different manners. Fatigability, reduced sleep, reduced sexual interest, apparent sadness, hostility and global ratings of abstinence improved significantly with the duration of the recovery period. Symptoms related to brain hyperexcitability such as fatigability, inner tension, insomnia and pains persisted for approximately 5 weeks. Of the biochemical parameters, the transaminases were normal in patients with more than 10 days of abstinence, while the levels of gamma-glutamyltransferase and HDL-cholesterol remained high for longer periods. The essential fatty acid status, measured by the fatty acid composition of serum lecithin, appeared to be normal only in patients with long recovery time. MAO in platelets was significantly lower than in the controls. The highest values were seen in the early recovery phase, which may indicate a temporary increase. Since polyunsaturated fatty acids are important constituents of synaptic membranes and since platelet MAO may reflect brain MAO, we consider these co-existing findings important in the interpretation of the psychiatric symptoms. The study demonstrated the existence of a subacute withdrawal syndrome lasting for 4-6 weeks.

Adult↗

Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation.

The post-mortem brain concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 16 parts of the brain from patients with no history of neurologic, psychiatric or metabolic illness. The causes of death were either ischemic heart disease, infections disease, cancer or accidents. Forty-two men with a mean age of 57 years (range 18-95 years) and 19 women with a mean age of 62 years (range 23-79 years) were included. The influence of several factors were studied: brain weight, time between death and autopsy, storage time before chemical analysis, age, sex, agonal status, cerebral arteriosclerosis, cancer, opiate treatment and time of death during the day. Most correlations between the 5-HT concentrations in different brain parts were positive, the strongest correlations in the basal ganglia and the limbic system. No consistent pattern of age-related 5-HT changes were found. The females had significantly higher 5-HIAA concentrations in the cortex of the gyrus hippocampus. Final hypoxia seemed to decrease 5-HT concentrations. Opiate treatment reduced 5-HT and increased 5-HIAA concentrations. A marked circadian variation of 5-HT was found, most pronounced in the hypothalamus, the limbic system and some neocortical areas.

Adolescent↗

Prevalence of dementia disorders in institutionalized Swedish old people. The work load imposed by caring for these patients.

The prevalence of dementia disorders were determined among 3,523 institutionalized patients aged 65 years or more in the county of Västerbotten. Approximately one-third of the clientele were considered demented. The prevalence was calculated to be 3.7% of the population in the county. The frequency of dementia disorders among the patients in the somatic long-stay wards, the nursing homes, and the mental hospital was rather similar (55-65%). A surprisingly high percentage of demented (17.1%) was found in the homes for the aged. The work load was highest in the somatic long-stay wards and in the nursing homes. Patients in the mental hospital, however, differed markedly from those in other institutions with higher scores for aggressive and disturbing behaviour, which accounted for the large number of patients in the mental hospital with maximal work load. The findings are discussed with regard to future institutional care of demented patients and point out the need for better education in psychiatric care for the staff.

Activities of Daily Living↗

Influence of depression and antidepressants on weight.

Depression is often combined with loss of appetite and weight. Treatment with some psychotropic drugs, especially many of the tricyclic antidepressives, causes weight gain. Zimelidine, an antidepressive drug with selective inhibitory effect on the reuptake of 5-hydroxytryptamine (5-HT) causes no weight gain in treated patients. As even weight loss is seen it can be discussed whether the drug has an inhibitory effect on feeding behaviour. This would be theoretical interest as animal experiments show that 5-HT may be an anorectic transmitter. It is also of practical importance as then the embarrassing side effect of weight gain might be avoided in antidepressive treatment.

Amitriptyline↗