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Biomedical subjects

G Bucht

Publications and source records attributed to G Bucht.

At least 19 recordsLinked to original sources

Residues in Torpedo californica acetylcholinesterase necessary for processing to a glycosyl phosphatidylinositol-anchored form.

Acetylcholinesterase from Torpedo californica (TcAChE) can be found as a glycosyl phosphatidylinositol (GPI)-anchored, membrane associated form. The C-terminal amino-acid sequence of the precursor protein resembles the signal peptide sequence found in proteins and enzymes destined for GPI-modification. Characteristics of such a signal peptide are a relatively polar stretch of amino acids, separating a cleavage- and modification-site (omega-site) residue from a hydrophobic C-terminus. We have introduced mutations, both at putative omega-sites and in the hydrophobic region, and analysed their effects on GPI-anchoring of TcAChE. Our results show that substitution of all three Ser residues in the region Ser542-Ser544 prevents GPI-modification and membrane anchoring. Individual substitution of each of these residues resulted in no or only a minor effect on the modification. We therefore conclude that more than one residue within this sequence can be utilised as the omega-site. Our analyses of double substitutions indicated that Ser543 and Ser544 are the preferred residues for GPI-modification. Moreover, the hydrophobic region is shown to be essential for GPI-anchoring of TcAChE.

Acetylcholinesterase

Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study.

In a population-based prospective study of epileptic seizures in adult s aged > 17 years, we identified 563 patients with possible seizures in a period of 34 months. Seizures were unprovoked in 160 patients, an incidence of 56 in 100,000 person-years. There was no difference in incidence between sexes. Age-specific incidences of unprovoked seizures increased sharply in men from age 60 years and in women from age 70 years. The incidence of unprovoked seizures in those aged > 65 years was 139 (men 166, women 116). The cumulative incidence of unprovoked seizures between the ages of 17 and 84 years was 4.6%. The proportion with an identified presumptive cause for unprovoked seizures increased with advancing age. A presumed etiology was identified in 77% of persons aged > 60 years. Stroke was the most common etiology, detected in 30% (incidence 16) and in 45% at ages > 60 years. Tumors were detected in 11% (incidence 6) and Alzheimer's disease was detected in 7% (incidence 4). Eighteen percent of patients were demented. Unprovoked seizures were partial in 68% of cases (incidence 38), and generalized in 16% (incidence 9). Another 13% of patients had generalized seizures, but seizure onset was not witnessed (incidence 7). In 16%, there was a delay of > 1 year from the first unprovoked seizure to initial diagnosis.

Adolescent

Physical restraints in geriatric care in Sweden: prevalence and patient characteristics.

OBJECTIVE: Physical restraints are used frequently in geriatric care to promote the safety of frail older patients. This study investigated the prevalence of the use of physical restraints in geriatric care and the way in which patient characteristics are related to the use of physical restraints. DESIGN: A point prevalence study of patients cared for in various types of geriatric settings. SETTING: Eight nursing homes, 15 old people's homes, a somatic geriatric clinic, and a psychogeriatric clinic in a health care district in northern Sweden. PARTICIPANTS: A total of 1325 patients, mean age 82 years, 64% of whom were women. MEASUREMENTS: The Multi-Dimensional Dementia Assessment Scale (MDDAS) was used to measure motor function, vision, hearing, speech, ADLs, behavioral symptoms, psychiatric symptoms, use of psychoactive drugs, and the physical and psychological workload of the staff. In addition, questions concerning the use of physical restraints were added to the instrument. RESULTS: Twenty-four percent of the patients were physically restrained. The highest prevalence was found in nursing homes and psychogeriatric care. Physical restraints were found to relate most strongly to cognitive impairment, impaired ADLs, and speech and walking ability. Ninety-four percent of the restrained patients were cognitively impaired. Other variables relating to the use of physical restraints were psychiatric symptoms and behavioral disturbances. CONCLUSIONS: This study has shown that physical restraints are used frequently in geriatric care in Sweden and that cognitive and physical impairments relate very closely to the use of physical restraints.

Activities of Daily Living

Falls leading to femoral neck fractures in lucid older people.

OBJECTIVE: To analyze the mechanisms of falls that result in femoral neck fractures among lucid older people. DESIGN: A cross-sectional study. SETTING: An orthopedic university hospital department. PARTICIPANTS: A consecutive series of 123 lucid patients, 65 years of age or more, who were admitted for femoral neck fractures. MEASUREMENTS: On admission, the subjects were interviewed about fracture accident characteristics, and falling mechanisms were classified. An arterial blood gas sample was taken from each patient soon after admission. Based on data regarding drug consumption and social and medical characteristics, a fall-risk index was calculated for each subject. RESULTS: It was ascertained that 95% of the fractures were caused by falls and < 2% were spontaneous. Most accidents (68%) took place indoors, 47% of the falls were classified as extrinsic, 24% as intrinsic, 7% as nonbipedal, and 22% remained unclassified. Almost all outdoor falls were extrinsic; however, intrinsic falls were as common as extrinsic falls indoors (P < .001). Extrinsic fallers presented a significantly lower fall-risk index score than subjects with fractures caused by intrinsic, nonbipedal, and unclassifiable falls. A large proportion of subjects (24%) wre hypoxemic (pO2 < 8 kPa) on admission, and patients who sustained fractures at night had lower oxygen tension than that of daytime fallers (P = .006). CONCLUSIONS: Accidental falls are the primary cause of femoral neck fractures. Preventive actions should be directed toward intrinsic, as well as extrinsic, risk factors for falls. Hypoxemia might be a risk factor for falls, especially those falls that occur at night.

Accidental Falls

Abnormalities in adrenal androgens, but not of glucocorticoids, in early Alzheimer's disease.

In an attempt to evaluate possible adrenal abnormalities in Alzheimer's disease (AD), prestimulus levels and ACTH-stimulated serum levels of steroid hormones, corticosteroid-binding globulin (CBG), and insulin-like growth factor I (IGF-I) were measured in 18 patients with early AD (8 men, 10 women; 74.6 +/- 6.5 years, mean +/- SD) and 19 healthy controls (10 men, 9 women; 74.2 +/- 7.6 years, mean +/- SD). Steroid hormone levels were measured before and after an intravenous bolus injection of 250 micrograms ACTH. AD per se had an independent influence on hormone levels when evaluated in MANOVA models. AD patients had significantly higher prestimulus levels of dehydroepiandrosterone and androstenedione (p = .04 and p = .003, respectively) with accentuated differences after ACTH (p = .02 and p < .001 for peak responses, respectively). Serum levels of cortisol, CBG, free cortisol, 17 alpha-hydroxyprogesterone (17 alpha-OHP), and IGF-I did not differ between groups. These abnormalities may have implications for neuronal degeneration as well as for behavioural symptoms in AD.

Adrenal Glands

Epidemiology and treatment of post-stroke depression.

Depression is a common and serious complication after stroke. According to epidemiological studies, at least 30% of stroke patients experience depression, both early and late after stroke. However, in clinical practice only a minority of the patients are diagnosed and even fewer are treated. There are several studies confirming the magnitude of the problem but the main conclusion which can be drawn from the few treatment studies published is that tricyclic antidepressants cannot be recommended for the treatment of post-stroke depression, mainly because of the high frequency of contraindications and adverse effects. Until now there has only been 1 double-blind, placebo-controlled treatment study from which some general conclusions can be drawn. The study evaluated a selective serotonin reuptake inhibitor (citalopram) and concluded that the drug was well tolerated and effective for the treatment of post-stroke depression. However, when treatment was initiated very early, both the treatment group and the placebo group improved equally during the first 7 weeks after stroke. This finding could indicate diagnosis difficulties during the first few weeks after stroke. A recent study, although small, comparing the combination of drugs with either noradrenergic (desipramine plus mianserin) or noradrenergic and serotonergic effects (imipramine plus mianserin) for post-stroke depression, indicated that drugs with the dual effect may be more effective. Many more double-blind placebo-controlled treatment studies and studies comparing the efficacy and adverse effects of various antidepressants in patients with post-stroke depression need to be conducted. According to 3 small studies, electroconvulsive therapy (ECT) seems to be quite well tolerated and therefore ECT may also be considered in the treatment of post-stroke depression. Future studies should also address the long term efficacy of treatment for post-stroke depression.

Aged

Residues important for folding and dimerisation of recombinant Torpedo californica acetylcholinesterase.

The three-dimensional crystal structure of the glycosyl phosphatidylinositol (GPI)-modified form of Torpedo acetylcholinesterase reveals the participation of Arg-44 and Glu-92 in a salt bridge and a hydrogen bond between Asp-93 and Tyr-96. To investigate the biological significance of these interactions, we have made amino acid replacements in this form of AChE: R44E, R44K, E92Q, E92L, D93N, and D93V. None of the introduced mutations affected the production of the acetylcholinesterase polypeptide significantly. However, the mutations introduced at position 92, as well as the D93V and R44E mutations, resulted in a total loss of surface located, active acetylcholinesterase. Replacement of Asp-93 with Asn resulted in a reduced amount of active enzyme. This mutant enzyme was indistinguishable from the wild-type enzyme regarding catalytic constants, but was more sensitive to thermal inactivation. The results show that the salt bridge and hydrogen bond involving residues Arg-44, Glu-92, and Asp-93 have important structural roles and are needed for correct folding, required for transport to the cell surface of TcAChE. The GPI-modified form of acetylcholinesterase is a disulfide bonded dimer. Cys-537 is shown to be required for the formation of the intersubunit disulfide bond in the dimer. Replacement with Ser resulted in the production of an enzyme, that migrates as a monomer upon non-reducing SDS-PAGE and has a lower stability compared to the dimeric wild-type enzyme.

Acetylcholinesterase

[Acute confusional states in patients with hip fractures can be prevented and treated].

Acute confusional states among the elderly constitute a manifest problem in most medical specialties. All too often the disoriented patient is deemed to be suffering from dementia, and no investigation is made of the background factors. Intervention studies have clearly shown that confusional states are both reversible and preventable.

Adrenocortical Hyperfunction

Physical health and cognitive ability among married long-term-care patients and among their spouses--a comparison between home care and nursing home care.

The purpose of this study was to establish whether physical health and cognitive function in married long-term patients or in their spouses determines why some patients are cared for in home care while others reside in nursing homes. Out of 38 married couples with a sick spouse cared for in a nursing home, 23 couples were studied; out of 34 couples with a sick spouse cared for in home care, 22 patients and 25 spouses were studied. The results showed no significant differences in physical health score either between the two groups of patients, or between the two groups of spouses. Both home-care patients and nursing home patients had low cognitive function scores, but nursing home patients had significantly lower scores. A multivariate analysis showed that physical health and cognitive function explained only 20% of patients' residence. Between the two groups of spouses there was no difference in cognitive function score. The conclusion is that physical health status and cognitive function explain only to a small extent why married long-term care patients are cared for in nursing homes or in home care.

Activities of Daily Living

A comparative study of the social conditions of spouses of long term patients cared for either in nursing homes or home care.

In order to study the social conditions of spouses of patients suffering from long term illnesses structured interviews were performed. The interviewees were divided into two groups: spouses of persons with chronic conditions cared for at home and spouses of patients cared for in nursing homes. Each group consisted of 27 spouses and there were no differences in physical health score, Mini mental score or ability to manage primary Activities of Daily Living functions between the groups. Home care spouses paid fewer visits to children, had fewer friends and paid fewer visits to friends and they also had time for hobbies or interests significantly more seldom (reading, visits to church) than nursing home spouses. There were no significant differences between the groups concerning sex, socio-economic class, housing conditions and amount of home health services. Their contact with children and their feelings of loneliness were reported to be the same.

Aged

Serum dehydroepiandrosterone sulfate in Alzheimer's disease and in multi-infarct dementia.

Circulating levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol were studied in 86 patients with dementia; 45 with Alzheimer's disease and 41 with multi-infarct dementia. Compared to an elderly control group, after adjustment for age and sex, patients with Alzheimer's disease were found to have lower serum levels of DHEAS. We found a covariation between serum albumin and DHEAS levels, which may be of importance regarding peripheral hormone concentration in patients with dementia. These findings may provide evidence for a role of DHEAS in amnestic disorder in humans, either reflecting or contributing to the course of dementing diseases.

Aged

Alzheimer's disease: paired helical filament immunoreactivity in cerebrospinal fluid.

A competitive enzyme-linked immunosorbent assay with high sensitivity has been developed for measuring ubiquitin reactivity of paired helical filaments (PHF). Using the assay, ubiquitin immunoreactivity was estimated in the cerebrospinal fluid (CSF) of 44 patients who had been clinically diagnosed as having Alzheimer's disease (AD) and of 38 control patients, including 20 neurological cases. Monoclonal antibody (mAb) 5-25 to isolated paired helical filaments was used. This mAb recognizes amino acids 64-76 of ubiquitin. The levels of ubiquitin immunoreactivity measured in CSF (twice diluted) were significantly higher in the AD (p less than 0.001) than in the control group. In only a minority of instances were values for ubiquitin levels the same in AD and control groups: on PHF-coated plates, immunoreactivity values for 77% of the AD CSF specimens were higher than those for 92% of the controls, and on ubiquitin-coated plates, values for 85% of the AD CSF specimens were higher than those for 88% of the controls. On immunoblots of both AD and control CSF, mAb 5-25 stained a series of protein bands. The free ubiquitin that is also present in the CSF was not labeled. No striking differences were detected in the immunoblot pattern of AD and control CSF. This study demonstrates the presence of quantitative differences in the conjugated ubiquitin in AD and control CSF.

Adult

Underdiagnosis and poor documentation of acute confusional states in elderly hip fracture patients.

STUDY OBJECTIVE: To determine the accuracy of diagnosis and documentation of acute confusional states (ACS) in the medical records of patients with hip fracture. DESIGN: The diagnosis of ACS in two prospective clinical studies was compared to its diagnosis in the medical records of the same patients on the same hospitalization. In order to determine if the simultaneous prospective study influences the diagnostic and documentary practices evidenced in the medical records, a further comparison was done by reviewing medical records of two series of patients seen some years prior to the prospective studies. SETTING: Patients with femoral neck fractures treated at a department of orthopedic surgery in a university hospital and one retrospective control sample from a department of general surgery in a county hospital. SUBJECTS: Two prospective samples of patients 65 years and older treated for femoral neck fractures (n = 111 and n = 57, respectively) and two earlier retrospective samples (n = 66 and n = 68, respectively). MEASUREMENTS AND MAIN RESULTS: All comparisons showed that both physicians and nurses diagnosed ACS unsatisfactorily and documented the patients' mental status poorly. The analysis of the two retrospective medical record control samples gave the same results. Neither the physicians nor the nurses used any kind of diagnostic instrument to detect cognitive disorders in the patients. CONCLUSIONS: ACS is a common and severe complication in elderly people treated for femoral neck fractures. Acute confusional states have, by definition, one or more causes that can often be identified and treated. Poor assessment and documentation is a threat to the patients as a correct diagnosis of ACS is a prerequisite for further assessment of its underlying causes and the consequent necessary medical and nursing care.

Acute Disease

A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures.

The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay.

Aged

Antibodies in serum of patients with Alzheimer's disease cause immunolysis of cholinergic nerve terminals from the rat cerebral cortex.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged