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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 37 records · Page 2Linked to original sources

Preservation of 5-hydroxytryptamine1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's disease.

The coupling of 5-hydroxytryptamine1A (5-HT1A) receptors to guanine nucleotide binding (G) proteins was investigated in membranes prepared from frontal and parietal cortices of control and Alzheimer's disease brains by characterising the effect of guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) on [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8-OH-DPAT) binding parameters. In the absence of guanine nucleotides, [3H]8-OH-DPAT bound to a single high affinity binding site in all membrane types. The number of [3H]8-OH-DPAT binding sites was significantly decreased in the parietal cortex of Alzheimer's disease samples compared with controls, whereas in the frontal cortex the number of binding sites remained unchanged. Gpp[NH]p reduced the [3H]8-OH-DPAT binding affinity and the number of binding sites to the same degree in both regions in control and Alzheimer's disease cases. [3H]8-OH-DPAT binding was inhibited in a concentration dependent manner with an IC50 value of approximately 1 microM in all cases. These results suggest that the 5-HT1A receptor-G protein complex is functionally intact in these regions in Alzheimer's disease brain.

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

Coupling of human brain cerebral cortical alpha 2-adrenoceptors to GTP-binding proteins in Alzheimer's disease.

The coupling of alpha 2-adrenoceptors to guanine nucleotide binding G-proteins was investigated in cerebral cortical membranes from control and Alzheimer's disease brain by characterizing the effects of MnCl2 and Gpp[NH]p on [3H]clonidine binding. The manganese induced elevation of [3H]clonidine binding was apparent in both control and Alzheimer's disease samples and the effect showed no significant difference between the two groups in the frontal cortex. However, the MnCl2 concentration dependence curves for control and Alzheimer's disease samples were significantly different from one another in the temporal cortex, whereas the pattern of stimulation by MnCl2 remained the same. The guanine nucleotide analogue, Gpp[NH]p inhibited [3H]clonidine binding in a concentration-dependent manner, the profiles of inhibition showing no significant differences between control and Alzheimer's disease samples. Analysis of the effect of Gpp[NH]p on [3H]clonidine saturation binding curves showed no significant differences between control and Alzheimer's disease samples in either frontal (Kd = 9.68 +/- 1.38, 9.1 +/- 2.6 nM; Bmax = 40.23 +/- 4.33, 44.3 +/- 9.4 fmol/mg, control and Alzheimer's disease values, respectively), or temporal (Kd = 11.61 +/- 4.04, 5.38 +/- 2.5 nM; Bmax = 52.0 +/- 14.0, 31.07 +/- 8.00 fmol/mg control and Alzheimer's disease values, respectively) cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment.

Alzheimer beta/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. By using an antibody directed against the cytoplasmic domain of APP, five species were resolved. Three of these, of molecular masses 106, 113, and 133 kDa, represent presumptive immature and mature isoforms of APP holoprotein. Two smaller proteins, of molecular masses 15 and 19 kDa, represent presumptive proteolytic carboxyl-terminal fragments of APP. The 133-, 113-, 106-, and 15-kDa species were found in both grey and white matter, whereas the 19-kDa species was found only in grey matter. Total APP immunoreactivity (sum of all five species) and the levels of the 113-, 106-, and 15-kDa species were not significantly different in brain samples from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. In contrast, the levels of the 133- and 19-kDa species increased 2- to 3-fold with age. A correlation was observed between the levels of the 133- and 19-kDa species, suggesting a possible precursor-product relationship. The size of the 19-kDa fragment indicated that it might have an intact beta/A4 domain and therefore be amyloidogenic. The age-dependent increase either in a mature APP isoform and/or in a putative amyloidogenic fragment could explain why Alzheimer disease is associated with advanced age.

Adolescent

Assay of a phosphatidylinositol bisphosphate phospholipase C activity in postmortem human brain.

The activity of a phospholipase C which hydrolyses exogenous phosphatidylinositol-4,5-bisphosphate [( 3H]PtdIns(4,5)P2) in membranes prepared from frozen postmortem human brain and rat brain was investigated. Enzyme characteristics were essentially similar in membranes prepared from frozen postmortem brain and fresh or frozen rat brain. The [3H]PtdIns(4,5)P2 solubilization and assay procedure employed resulted in an efficient availability of the substrate for the enzyme. The non-hydrolysable guanosine triphosphate analogue guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) stimulated hydrolysis rapidly with a half maximum activity of approximately 25 microM. This stimulation was not specific for guanine nucleotides as ATP, imidodiphosphate and pyrophosphate also caused enzyme activation. However these activation effects could be distinguished by the polyanion spermine. The non-hydrolysable guanine dinucleotide analogue guanosine 5'-[beta-thio]diphosphate acted as a partial agonist thereby inhibiting the stimulatory effect of Gpp[NH]p. Gpp[NH]p-stimulated enzyme activity showed a maximum response in the presence of 1 mM deoxycholate and displayed a pH optima in the range 7.0-7.5. PtdIns(4,5)P2 hydrolysis was observed in the absence of added calcium, but hydrolytic cleavage was inhibited in the presence of divalent ion chelators. Magnesium inhibited PtdIns(4,5)P2 hydrolysis in a concentration-dependent manner. Elucidation of these aspects of the phosphatidylinositol cycle in normal human postmortem brain will permit comparative studies in CNS disease states.

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

Wish to transfer to other jobs among long-term care workers.

This study is based on questionnaires that were sent to the homes of health care personnel working in geriatric care (N = 583) and acute care (N = 328). The purpose was to investigate differences between these groups of personnel regarding job assignment, intention to transfer to another job, attitudes towards demented patients, and the experience of burnout. The results showed that more persons working in acute care were self-assigned to their jobs than those working in geriatric care. More persons in geriatric care stated a wish to transfer to another job in the health care field than those in acute care. The personnel who constantly work with demented patients showed the most positive attitudes towards this group of patients. A larger proportion of personnel with high burnout scores wanted to transfer to another job, compared to those with low burnout scores.

Aged

Staff burnout in dementia care--relations to empathy and attitudes.

Sixty nursing staff in geriatric and psychogeriatric care (RNs, LPNs and nurse's aides) were selected to be studied on two occasions with an interval of one year regarding the relationships between their experience of burnout, empathy and attitudes towards demented patients. A semistructured interview was performed on the second occasion to learn more about their work experience and to relate the ratings of burnout, empathy and attitudes to their experience at work. The staff's experience of burnout changed from a mean score of 2.7 in 1987 to 2.5 in 1988. Their empathic ability was moderately high and increased from 398 (m) in (1987) to 450 (m) in 1988. The attitudes of staff remained unchanged from 1987 to 1988 and no differences were found regarding the staff's age, place of work or time at present place of work. As for the staff's empathy, there was no difference with respect to sex, category of staff or place of work. RN's showed the most positive attitudes towards demented patients both in 1987 and 1988 and differed compared to the nurse's aides and LPN's. Burnout correlated with lower empathy and less positive attitudes in the staff. Regression analysis showed that 'experience of feed-back at work' and 'time spent at present place of work' were the most important factors when explaining burnout among the staff. Staff with high empathy experienced "a close contact with the patient" as the most stimulating factor at work while staff with low empathy experienced "improvement of the patient's health" and "contact with colleagues" as the most stimulating factors. The importance of counteracting burnout in the care of demented patients is stressed.

Adolescent

Regional distribution of somatostatin receptor binding and modulation of adenylyl cyclase activity in Alzheimer's disease brain.

We have previously reported a reduction in the inhibitory effect of somatostatin on adenylyl cyclase activity in the superior temporal cortex of a group of Alzheimer's disease cases, compared to a group of matched controls. In the present study, the levels of high affinity 125I-Tyr11-somatostatin-14 binding, its modulation by guanine nucleotides and the effects of somatostatin on adenylyl cyclase activity have been measured in preparations of frontal cortex, hippocampus, caudate nucleus and cerebellum from the same patient and control groups. A significant reduction in 125I-Tyr11-somatostatin-14 binding was observed in the frontal cortex, but not other regions, of the Alzheimer's disease group, compared with control values. The profiles of inhibition of specific 125I-Tyr11-somatostatin-14 binding by Gpp(NH)p were similar in all regions in both groups. No significant differences in basal, forskolin-stimulated, or somatostatin and neuropeptide Y inhibitions of adenylyl cyclase activity were found between the two groups. The pattern of change of somatostatin binding in the Alzheimer's disease cases observed in the present study differs from the reported pattern of loss of somatostatin neurons and may be secondary to the degeneration of somatostatin receptor-bearing cholinergic afferents arising from the nucleus basalis. The results of this study indicate that impaired somatostatin modulation of adenylyl cyclase is not a global phenomenon in Alzheimer's disease brain and also that there are no major disruptions of somatostatin receptor-G-protein coupling or of adenylyl cyclase catalytic activity in this disorder.

Adenylyl Cyclases

ADL performance and dependency on nursing care in patients with hip fractures and acute confusion in a task allocation care system.

In a prospective study 35 patients operated on for cervical hip-fractures were followed with respect to Acute Confusional State (ACS), problems of basic nursing care and dependency on care-givers. Fifteen patients became acutely confused after the fracture. They turned out to be more dependent on help from others than the non-confused patients were even before the fracture. They rapidly reached a significantly higher level of dependence than the non-confused patients and remained on that level throughout the study month. Six months after the fracture the post-operatively confused patients were still highly dependent on care-givers, significantly more than they were before the fracture. Only three of them were not hospitalised. All the non-confused patients lived in their own homes six months after the fracture and had regained the same level of independence as before it. These findings will be discussed in relation to the organisation of the nursing care. Task allocation nursing care was applied in the wards. A model for the development of dependency in acutely confused hip-fracture patients will be presented and suggestions for how to reduce nurse/patient dependency induced by nursing care will be made.

Activities of Daily Living

Abilities and activities of patients with dementia in day hospitals.

The proportion of individuals with dementia is increasing in all kinds of institutions. Specialised day hospitals are now being developed as an alternative to long term care for the demented. Twelve day hospital wards, with 312 individuals suffering from dementia, were included in a study aiming to assess functional abilities and frequencies of participation in different activities. Eighty-nine per cent of the day hospital patients could be classified as having a dementia disease. Seventy-eight per cent of the population were dependent on some kind of help from a caregiver in the performance of ADL activities. The most common occupations that could be seen in the programmes were physical activities, entertainment, and personal care activities. The activities were often undertaken as large group activities, often including more than ten patients. The functional abilities that characterise the population are comparable with those of the population living in pensioners' service blocks with full board.

Activities of Daily Living

Care of demented patients with severe communication problems.

Two time-studies and an interview study were carried out at a geriatric clinic. The aim was to elucidate how much time caregivers use for direct patient care in their contact with severely demented patients compared with non-demented patients as well as how they experience the care of demented patients in a task assignment care system. The analysis showed that more time was used to help non-demented patients than demented patients with the same ADL-performance. Five types of patient reactions to communicative attempts made by the caregivers were described: the patient seems to enjoy contact, he avoids contact, contact leads to aggression, he reacts only sporadically to contact and he does not show any reactions to it. The caregivers described negative reactions to demented patients with communication problems. Communication problems seem to be a threat to caregivers' commitment.

Activities of Daily Living

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

International comparison of long-term care: the need for resident-level classification.

Differences between long-term care facilities in Stockholm (1134 residents) and New York (95,000 residents statewide) were examined. The comparison employed a resident classification system, Resource Utilization Groups (RUG-II), which links individuals' characteristics to resource use. Distributions of Activity of Daily Living functionality and RUG-II categories demonstrated significant differences between these two populations, with the Stockholm facilities more akin to the heavier care skilled nursing facilities in New York. These differences may indicate different uses of long-term care beds in the United States and Sweden and demonstrate the need for resident-level classification systems in cross-national studies.

Activities of Daily Living

Prevalence of Alzheimer's disease and other dementias in an elderly urban population: relationship with age, sex, and education.

We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimer's disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education.

Age Factors

Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease.

Cerebro-spinal fluid (CSF) and blood levels of aluminium, cadmium, calcium, copper, lead, magnesium, and mercury were studied in 24 subjects with dementia of the Alzheimer type (DAT) and in 28 healthy volunteers. Furthermore, arsenic, bromine, chrome, iron, manganese, nickel, rubidium, selenium, strontium, and zinc were measured only in blood. There were significant changes in the DAT group when compared to the controls. The plasma levels of aluminium, cadmium, mercury and selenium were increased and the contents of iron and manganese were lower in the DAT group as compared to control subjects. In CSF there were low levels of cadmium and calcium and increased content of copper in DAT cases. Iron and zinc levels in blood and calcium in both blood and CSF of DAT patients correlated with memory and cognitive functions. Iron, manganese and strontium levels of DAT sufferers in blood and aluminium in CSF were related with changes in behaviour.

Aged