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Biomedical subjects

B Olofsson

Publications and source records attributed to B Olofsson.

At least 19 recordsLinked to original sources

A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture.

INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture. METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged >or=70 years. RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 - 0.76, p=0.006] for the total sample and 0.07 (95% CI: 0.01-0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group. CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia.

Accidental Falls↗

Altered homeostasis of extracellular matrix proteins in joints of standardbred trotters during a long-term training programme.

This study evaluates how strenuous training, age and lameness influence the release of cartilage oligomeric matrix protein (sf-COMP), aggrecan and collagen type II into synovial fluid in 28 (19.5-40 months) Standardbred trotters (STB), during a long-term training programme (24 months). All the horses were trained by the same trainer and were healthy on entering the training programme. Synovial fluid (sf) from the left middle carpal joint in each subject was sampled every third month. Enzyme-linked immunosorbent assay was used to determine the concentrations of sf-COMP, sf-aggrecan and sf-collagen type II. Concentration of sf-COMP decreased with increasing age and total days of training. The concentration of sf-COMP was found similarly related to both age and total days of training, so they could not be differentiated. It was also shown that the concentration of collagen type II degradation products increased with total days of training. The study shows that extensive and long-term training programme induces metabolic changes in articular cartilage exemplified by reduced release and synthesis of COMP. This is most likely due to strenuous training leading to inappropriate load on the articular cartilage.

Animals↗

RhoGDI-3, a promising system to investigate the regulatory function of rhoGDIs: uncoupling of inhibitory and shuttling functions of rhoGDIs.

rhoGDIs (Rho GDP dissociation inhibitors) are postulated to regulate the activity and the localization of small G-proteins of the Rho family by a shuttling process involving extraction of Rho from donor membranes, formation of inhibitory cytosolic rhoGDI/Rho complexes, and delivery of Rho to target membranes. However, the role of rhoGDIs in site-specific membrane targeting or extraction of Rho is still poorly understood. We investigated here the in vivo functions of two mammalian rhoGDIs: the specific rhoGDI-3 and the well-studied rhoGDI-1 (rhoGDI) after structure-based mutagenesis. We identified two sites in rhoGDIs, forming conserved interactions with their Rho target, whose mutation results in the uncoupling of inhibitory and shuttling functions of rhoGDIs in vivo. Remarkably, these rhoGDI mutants were detected at Rho-induced membrane ruffles or protrusions, where they co-localized with RhoG or Cdc42, probably identifying for the first time the site of extraction of a Rho protein by a rhoGDI in vivo. We propose that these mutations act by modifying the steady-state kinetics of the shuttling process regulated by rhoGDIs, such that transient steps at the cell membranes now become detectable. They should provide valuable tools for future investigations of the dynamics of membrane extraction or delivery of Rho proteins and their regulation by cellular partners.

Guanine Nucleotide Dissociation Inhibitors↗

Opening up: psychiatric nurses' experiences of participating in reflection groups focusing on the use of coercion.

Psychiatric staff report that the use of coercion towards patients in psychiatric care engenders feelings of discomfort and conflicts. The aim of this study was to describe psychiatric nurses' experiences of participating in reflection groups focused on the use of coercion, in relation to their views regarding systematic clinical supervision and staff support. Twenty-one nurses who had participated in reflection groups were interviewed retrospectively. The structured interview focused on: (i) their views of clinical supervision and support in general; (ii) their views of clinical supervision and support specifically concerning the use of coercion; and (iii) their experiences of participating in groups reflecting the use of coercion. Nurses were largely positive about participating in reflection groups, as expressed in the subthemes: having time for reflection; being confirmed; gaining new perspectives; sharing fellowship with colleagues; and relating more effectively to patients. Complications concerning participation in the reflection groups and other forms of clinical supervision as reported by nurses were: providing time for participation; having a common aim; being vulnerable in difficult situations; and assuming that the need for supervision and support could indicate that they were not coping with their job.

Adult↗

Health-related quality of life during treatment of elderly patients with hypertension: results from the Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) was a multinational, randomised, double-blind study to assess the effects of candesartan 8-16 mg daily on cardiovascular events and cognitive function in elderly patients (aged 70-89 years) with mild to moderate hypertension. A total of 4937 patients were randomised to candesartan or placebo with other antihypertensive drugs (mostly diuretics, beta-blockers, and calcium antagonists) added as needed to control blood pressure. Only 16% of the patients in the control group received placebo alone. The mean follow-up was 3.7 years. The aim of this health-related quality of life (HRQL) substudy analysis was to investigate changes in HRQL during antihypertensive treatment, and possible differences in patients receiving candesartan-based or other antihypertensive treatment. Three validated HRQL instruments were used: the Psychological General Well-being (PGWB) Index, the Subjective Symptoms Assessment Profile (SSA-P), and the EuroQoL Health Utility Index (EuroQoL). The HRQL was generally good at baseline and well preserved during follow-up in the presence of substantial blood pressure reductions in both treatment groups. Several of the observed changes in score from baseline to last visit favoured candesartan-based compared to control treatment, particularly the changes in PGWB Anxiety (-0.5 vs -1.0, P=0.01), PGWB Positive well-being (-0.8 vs -1.1, P=0.04), SSA-P Cardiac symptoms (0.03 vs 0.10, P=0.03), and EuroQoL Current health (-3.1 vs -5.3, P=0.008). This favourable result may be related to the somewhat lower blood pressure associated with candesartan-based treatment. In conclusion, there should be no reason to withhold modern antihypertensive therapy in elderly patients due to concerns for a negative effect on HRQL.

Aged↗

Struggling for hopefulness: a qualitative study of Swedish women who self-harm.

There has been an increase in the number of Swedish psychiatric patients who self-harm, yet self-harm is seldom described in published research. The aim of this study was to describe how people who self-harm experience received care and their desired care. Nine participants, all Swedish women who had been treated for inpatient or outpatient psychiatric care, narrated their experiences of care for self-harm. Using qualitative content analysis, two themes were formulated: 'Expecting to be confirmed while being confirmed fosters hopefulness'; and, 'Expecting to be confirmed while not being confirmed stifles hopefulness'. Each of these themes emerged from five subthemes that clustered around positive and negative aspects of being seen-not being seen, being valued-being stigmatized, being connected-disconnected, being believed-doubted, and being understood-not being understood. Of significance is for nurses to view persons who self-harm as human beings and to grasp the importance of being confirmed by staff that can foster hopefulness in persons who self-harm, yet realize the possibility of the paradoxical nature of hopefulness and being confirmed.

Adult↗

Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.

Adrenergic beta-Antagonists↗

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.

Animals↗

Experiences of coercion in psychiatric care as narrated by patients, nurses and physicians.

AIM: The aim of the study was to increase understanding of psychiatric patients', nurses' and physicians' experience of coercion, in relation to their own and the other parties' experiences. METHODS: Seven triads of patient, nurse and physician narrated their experiences of the same coercive event. The 21 interviews were analysed focusing on narrative elements. RESULTS: The nurse and physician narratives revealed that they felt unable to connect with the patients, while the patients told us that they wanted more human contact with nurses and physicians. All three parties expressed the belief that interpersonal relationships and the human contact were important. The nurses and physicians stated that knowing the patient made them feel easier about using coercion and that their actions were less violating for the patient. The patients stated that human contact alleviated their feeling of discomfort and made them feel more secure when subjected to coercion. CONCLUSION: The salient aspect described by all three parts was the importance of human contact and having a mutual relationship. These findings indicate a need for more dialogue between patients and staff. The dialogue should aim at making staff understand patients' feelings better regarding coercion and at informing the patients about the coercive measures.

Adult↗

A plea for respect: involuntarily hospitalized psychiatric patients' narratives about being subjected to coercion.

Eighteen involuntarily hospitalized psychiatric patients narrated their experiences of being subjected to coercion and their thoughts on how to prevent the coercion. A qualitative content analysis identified recurring themes, which were incorporated in two core themes describing the participants' experience. The core theme Not being respected as a human being included most of their narrated experiences, described in the themes Not being involved in one's own care, Receiving care perceived as meaningless and not good, and Being an inferior kind of human being. The core theme Being respected as a human being included a minor part of the narrated experiences and how the participants wanted things to be, described in the themes Being involved in one's own care, Receiving good care, and Being a human being like other people. The participants' plea for respect is discussed in relation to the ongoing deinstitutionalization of psychiatric care and the need for attitude changes in care and community, leading to the treating of mentally disordered people with more respect.

Adult↗

A regio- and stereodivergent synthesis of vic-amino alcohols

A regio- and stereodivergent synthesis of vic-amino alcohols starting from vinylepoxides is described. The developed strategy focuses on the propensity of vinylepoxides and vinylaziridines to be ring-opened at the allylic position by suitable nucleophiles and makes use of reactions that perform such tasks selectively with either retention or inversion of configuration.

Journal Article↗

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

Aged↗

Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia.

Vascular endothelial growth factor (VEGF) is a key modulator of angiogenesis during development and in adult tissues, whereas the related VEGF-C has been shown to induce both lymphangiogenesis and angiogenesis. To better understand the specific functions of these growth factors, we have here analyzed their binding to sections of mouse embryonic and adult tissues and compared the distribution of the bound growth factors with the expression patterns of the 3 known members of the VEGF receptor family as well as with neuropilin-1, a coreceptor for VEGF(165). Partially overlapping patterns of VEGF and VEGF-C binding were obtained in embryonic tissues, consistent with the expression of all known VEGF receptors by vascular endothelial cells. However, the most striking differences of binding were observed in the developing and adult heart, in which VEGF decorated all vessels, whereas strong VEGF-C signals were obtained only from epicardial vessels. In the lymph nodes, VEGF and VEGF-C showed distinct binding patterns in agreement with the differential location of their specific receptors. These results show that both VEGF-C and VEGF target embryonic blood vessels, whereas a more selective binding of VEGF-C occurs to its lymphatic vascular receptor in certain adult tissues. Our results suggest that VEGF and VEGF-C have both overlapping and distinct activities via their endothelial receptors.

Animals↗

Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1.

Vascular endothelial growth factor B (VEGF-B) is expressed in various tissues, especially strongly in the heart, and binds selectively to one of the VEGF receptors, VEGFR-1. The two splice isoforms, VEGF-B(167) and VEGF-B(186), have identical NH(2)-terminal cystine knot growth factor domains but differ in their COOH-terminal domains which give these forms their distinct biochemical properties. In this study, we show that both splice isoforms of VEGF-B bind specifically to Neuropilin-1 (NRP1), a receptor for collapsins/semaphorins and for the VEGF(165) isoform. The NRP1 binding of VEGF-B could be competed by an excess of VEGF(165). The binding of VEGF-B(167) was mediated by the heparin binding domain, whereas the binding of VEGF-B(186) to NRP1 was regulated by exposure of a short COOH-terminal proline-rich peptide upon its proteolytic processing. In immunohistochemistry, NRP1 distribution was found to be overlapping or adjacent to known sites of VEGF-B expression in several tissues, in particular in the developing heart, suggesting the involvement of VEGF-B in NRP1-mediated signaling.

Animals↗

Localization of VEGF-B in the mouse embryo suggests a paracrine role of the growth factor in the developing vasculature.

Vascular endothelial growth factor B (VEGF-B) is structurally closely related to VEGF and binds one of its receptors, VEGFR-1. In situ hybridization and immunohistochemistry were used to localize VEGF-B mRNA and protein in embryonic mouse tissues. In 8.5-17.5 day embryos, VEGF-B was most prominently expressed in the developing myocardium, but not in the cardiac cushion tissue. The strong expression in the heart persisted at later developmental stages, while weaker signals were obtained from several other tissues, including developing muscle, bone, pancreas, adrenal gland, and from the smooth muscle cell layer of several larger vessels, but not from endothelial cells. VEGF-B is likely to act in a paracrine fashion, as its receptor is almost exclusively present in endothelial cells. VEGF-B may have a role in vascularization of the heart, skeletal muscles and developing bones, and in paracrine interactions between endothelial and surrounding muscle cells.

Animals↗

Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling.

The small G proteins of the Ras family act as bimodal relays in the transfer of intracellular signals. This is a dynamic phenomenon involving a cascade of protein-protein interactions modulated by chemical modifications, structural rearrangements and intracellular relocalisations. Most of the small G proteins could be operationally defined as proteins having two conformational states, each of which interacts with different cellular partners. These two states are determined by the nature of the bound nucleotide, GDP or GTP. This capacity to cycle between a GDP-bound conformation and a GTP-bound conformation enables them to filter, to amplify or to temporise the upstream signals that they receive. Thus the control of this cycle is crucial. Membrane anchoring of the proteins in the Ras family is a prerequisite for their activity. Most of the proteins in the Rho/Rac and Rab subfamilies of Ras proteins cycle between cytosol and membranes. Then the control of membrane association/dissociation is an other important regulation level. This review will describe one family of crucial regulators acting on proteins in the Rho/Rac family-the Rho guanine nucleotide dissociation inhibitors, or RhoGDIs. As yet, only three RhoGDIs have been described: RhoGDI-1, RhoGDI-2 (or D4/Ly-GDI) and RhoGDI-3. RhoGDI 1 and 2 are cytosolic and participate in the regulation of both the GDP/GTP cycle and the membrane association/dissociation cycle of Rho/Rac proteins. The non-cytosolic RhoGDI-3 seems to act in a slightly different way.

Amino Acid Sequence↗

Current biology of VEGF-B and VEGF-C.

Endothelial growth factors and their receptors may provide important therapeutic tools for the treatment of pathological conditions characterised by defective or aberrant angiogenesis. Vascular endothelial growth factor (VEGF) is pivotal for vasculogenesis and for angiogenesis in normal and pathological conditions. VEGF-B and VEGF-C provide this gene family with additional functions, for example, VEGF-C also regulates lymphangiogenesis.

Animals↗

Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators.

BACKGROUND: Chronic heart failure (CHF) is an increasing burden to health care. Pharmacological treatment with angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalizations in patients with low left ventricular ejection fraction (LVEF). Despite these therapies, morbidity and mortality remains problematic. Furthermore, 30% to 50% of patients with CHF have a preserved LVEF. It is not known if treatments are of benefit in this group. DESIGN: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure. Patients with systolic dysfunction, tolerant or intolerant to an ACE-inhibitor, and patients with preserved systolic function are included. Specifically, the CHARM program consists of 3 independent, parallel, placebo-controlled studies in patients with (1) LVEF less than or equal to 40%, ACE-inhibitor treated (n = 2,300); (2) LVEF less than or equal to 40%, ACE-inhibitor intolerant (n = 1,700); (3) LVEF greater than 40%, not treated with ACE inhibitors (n = 2,500). The 3 studies will be combined to evaluate the effect of candesartan cilexetil on all-cause mortality in the broad spectrum of symptomatic heart failure. The primary objective in each trial is to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization. Other endpoints include the effects on myocardial infarction, all-cause hospitalization, and resource utilization. CHARM is intended to randomize 6,500 patients with symptomatic heart failure from 26 countries in Europe, the United States, Canada, South Africa, and Australia. The CHARM program started to enroll patients in March 1999. The follow-up period is a minimum of 2 years. The study is expected to end in the third quarter of 2002.

Adolescent↗