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Biomedical subjects

G Bucht

Publications and source records attributed to G Bucht.

At least 37 records · Page 2Linked to original sources

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↗

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

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 presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗

Acute confusional states in elderly patients treated for femoral neck fracture.

The aims of this study were to estimate the incidence of acute confusional state (ACS), its predisposing factors and consequences in 111 consecutive patients operated for fractured neck of the femur. The incidence of ACS was 61 percent and the predicting factors were old age and dementia. Drugs with anticholinergic effect, depression, and previous stroke were factors that seemed to be associated with the development of ACS. Ninety-two percent of the patients who had severe perioperative blood pressure drops developed ACS. The consequences of ACS were prolonged ward-stay at the orthopedic department, a greater need for long-term care after discharge, and poor walking ability at discharge and six months after surgery. The confused patients also had more complications, such as urinary problems, feeding problems and decubital ulcers, as compared with the nonconfused patients.

Aged↗

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↗

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↗

Reactivation of nerve agent inhibited human acetylcholinesterases by HI-6 and obidoxime.

Acetylcholinesterase was purified from human caudate nucleus and skeletal muscle. The enzyme preparations were used to study aging and reactivation by HI-6 and obidoxime after inhibition by soman and its isomers. HI-6 was found to be the most potent reactivator. For both enzyme preparations a higher reactivatability and a higher rate of aging were observed after inhibition by C+-soman than after inhibition by C(-)-soman. Aging was retarded by propidium diiodide. Reactivation by the two oximes was also studied after inhibition by tabun, sarin and VX. Tissue homogenates were used for this part of the work. Our conclusion is that HI-6 is superior to obidoxime for human acetylcholinesterases inhibited by soman and sarin, while obidoxime is better towards tabun-inhibited enzyme.

Acetylcholinesterase↗

Extraneural cholinergic markers in Alzheimer's and Parkinson's disease.

Muscarinic and nicotinic binding sites were analysed in lymphocytes from patients with Alzheimer's disease, Multi-infarct dementia, Parkinson's disease and age- matched controls. A significant decrease in the number of both muscarinic and nicotinic binding sites was obtained in lymphocytes from Alzheimer patients while in Parkinson patients a significant decrease was found only in the nicotinic binding sites. Using butyrylthiocholine as substrate, no change was observed in cholinesterase activity in plasma from Alzheimer patients, whereas a significant decrease in plasma cholinesterase activity was found in Parkinson patients.

Aged↗