[The rumour about the death of debriefing is significantly exaggerated!].
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Biomedical subjects
Publications and source records attributed to G Larsson.
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Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleotides. Eukaryotes have an alpha(2)beta(2) form of RNR consisting of two homodimeric subunits, proteins R1 (alpha(2)) and R2 (beta(2)). The R1 protein is the business end of the enzyme containing the active site and the binding sites for allosteric effectors. The R2 protein is a radical storage device containing an iron center-generated tyrosyl free radical. Previous work has identified an RNR protein in yeast, Rnr4p, which is homologous to other R2 proteins but lacks a number of conserved amino acid residues involved in iron binding. Using highly purified recombinant yeast RNR proteins, we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. This complex sediments at 5.6 S as a betabeta' heterodimer in a sucrose gradient. In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer, where Rnr4p plays an important role in the interaction between the alpha(2) and the betabeta ' subunits. The specific activity of the Rnr2p complexed with Rnr4p is 2,250 nmol deoxycytidine 5'-diphosphate formed per min per mg, whereas the homodimer of Rnr2p shows no activity. This difference in activity may be a consequence of the different conformations of the inactive homodimeric Rnr2p and the active Rnr4p-bound form, as shown by CD spectroscopy. Taken together, our results show that the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit.
The dimensionality of the Impact of Event Scale (IES) was analyzed using structural equation modeling (SEM). Responses from 321 individuals (62% response) who had experienced a mass murder of seven people 8 months earlier were obtained. A model with a general factor and three subordinate specific factors--Intrusiveness, Avoidance, and Sleep Disturbance--was developed. Scores on the original IES subscales and the SEM factors were related to scores on the General Health Questionnaire. It was concluded that the original subscales could, to a certain degree, be regarded as a reflection of negative affectivity. A more differentiated pattern emerged using the specific latent variables from the SEM analysis.
Cell respiration is catalyzed by the heme-copper oxidase superfamily of enzymes, which comprises cytochrome c and ubiquinol oxidases. These membrane proteins utilize different electron donors through dissimilar access mechanisms. We report here the first structure of a ubiquinol oxidase, cytochrome bo3, from Escherichia coli. The overall structure of the enzyme is similar to those of cytochrome c oxidases; however, the membrane-spanning region of subunit I contains a cluster of polar residues exposed to the interior of the lipid bilayer that is not present in the cytochrome c oxidase. Mutagenesis studies on these residues strongly suggest that this region forms a quinone binding site. A sequence comparison of this region with known quinone binding sites in other membrane proteins shows remarkable similarities. In light of these findings we suggest specific roles for these polar residues in electron and proton transfer in ubiquinol oxidase.
Cytochrome bo(3) ubiquinol oxidase has been successfully purified for crystallization. Single crystals of this integral membrane protein diffract X-rays to 3.5 A resolution and belong to the orthorhombic space group C222(1). From the diffraction data, the unit-cell parameters were determined to be a = 91.3, b = 370.3, c = 232.4 A. The crystals have a solvent content of 59% and contain two molecules per asymmetric unit. A search model generated from the structures of cytochrome c oxidase from Paracoccus denitrificans and the extrinsic domain of cytochrome bo(3) ubiquinol oxidase from Escherichia coli was used for molecular-replacement studies, resulting in a solution with sensible molecular packing.
Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for DNA recognition. We have determined a high-quality nuclear magnetic resonance (NMR) structure of the DNA-binding homeodomain of the insulin gene enhancer protein Isl-1 (Isl-1-HD). It forms the first solution structure of a homeodomain from the LIM family. It contains a well-defined inner core (residues 12-55) consisting of the classical three-helix structure observed in other homeodomains. The N terminus is unstructured up to residue 8, while the C terminus gradually becomes unstructured from residue 55 onwards. Some flexibility is evident in the loop parts of the inner core. Isl-1-HD has, despite its low sequence identity (23-34 %), a structure that is strikingly similar to that of the other homeodomains with known three-dimensional structures. Detailed analysis of Isl-1-HD and the other homeodomains rationalizes the differences in their temperature stability and explains the low stability of the Isl-1-HD in the free state (tm 22-30 degrees C). Upon DNA binding, a significant stabilization occurs (tm>55 degrees C). The low stability of Isl-1-HD (and other mammalian homeodomains) suggests that in vivo Isl-1-HD recognizes its cognate DNA from its unfolded state.
To improve routines in clinical practice and research, it is important that new tests are thoroughly evaluated before they gain widespread application. This includes establishing the reliability and validity of the new test. The purpose of this study was to establish the construct and criterion validity of cough-induced leak point pressure (CILPP) measurement. Data on CILPP, maximum urethral pressure (MUP), and a short-term pad test from a phase-I trial of a new pharmacological agent (LS 4416), developed for the treatment of stress incontinence, was used to test the validity of CILPP. Fifteen post-menopausal women with stress incontinence were studied. Phenylpropanolamine (PPA) was used as a positive control. Administration of PPA produced a statistically significant increase in MUP and CILPP. There was a significantly better effect of treatment, expressed as an increase in MUP at 1.5 hr, when PPA was used than with placebo or LS 4416. When CILPP was used to detect change after therapy, PPA produced a significantly greater increase in CILPP than did placebo (least square mean of difference 17.25, P = 0.0202). There was a moderate but statistically significant correlation between CILPP and the short-term Pad Test. Construct validity was demonstrated by the ability of CILPP to detect limited improvement in patients with stress incontinence. Criterion validity was established by the correlation of CILPP to a short-term Pad Test. We propose that, thanks to its greater methodological qualities, leak point pressure measurement should be adopted as a standard method to ascertain the effect of treatment in patients with stress incontinence. Neurourol. Urodynam. 18:591-602, 1999.
OBJECTIVES: To summarize the efficacy and safety of tolterodine from the pooled data of four multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group Phase II studies in patients with urodynamically proved overactive bladder (detrusor instability or detrusor hyperreflexia) and to analyze the concentration-effect relation. METHODS: After a 1-week run-in period to establish baseline values, 319 patients were randomized to receive placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily. Micturition diary and urodynamic variables and subjective urinary symptoms were assessed after 2 weeks of treatment. Patients were classified as "extensive" or "poor" metabolizers of tolterodine on the basis of serum levels of tolterodine. RESULTS: A per-protocol analysis of efficacy in 262 patients showed dose-related improvements in micturition diary and urodynamic variables. A dosage of 4 mg twice daily was, however, associated with an increase in residual urinary volume. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable between placebo and tolterodine dosages of 2 mg twice daily. No serious drug-related adverse events were observed, and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. Changes in urodynamic variables were found to be related to the sum of unbound serum concentrations of tolterodine and its major active 5-hydroxymethyl metabolite. In poor and extensive metabolizers of tolterodine, exposure to the sum of these active moieties was similar, and the efficacy and safety profiles were comparable. CONCLUSIONS: The results of this pooled data analysis indicate that tolterodine offers an effective treatment for patients with urinary symptoms attributable to overactive bladder. The optimal dosage is 1 to 2 mg twice daily, irrespective of metabolic phenotype.
BACKGROUND: Little is known about the health-related-quality of life (HRQoL) of patients with endocrine gastrointestinal tumours. In this study, HRQoL was investigated in long-term survivors of endocrine GI tumours. PATIENTS AND METHODS: A questionnaire including the EORTC QLQ-C30 and ratings of importance of and satisfaction with a variety of HRQoL aspects was mailed to patients with carcinoid tumours (n = 64), or endocrine pancreatic tumours (EPT, n = 55). Median time since diagnosis was 120 months (range 60-360). The majority of patients (77 of 119) had ongoing treatment. RESULTS: The EORTC QLQ-C30 ratings suggest that in spite of a long disease duration and treatment, patients perceived their HRQoL as relatively good. There were no major differences in HRQoL ratings between patients with carcinoid tumours and those with EPT. Patients whose ratings of importance was higher than their ratings of satisfaction with a specific HRQoL aspect also evidenced a low HRQoL for that aspect. CONCLUSIONS: The results indicate that survivors of endocrine GI tumours enjoy a relatively good HRQoL and suggest that importance > satisfaction discrepancies identify patients with a low quality of life.
The aim was to explore the relationship between patients' perceptions of the quality of care and their sense of coherence. The sample consisted of 782 Swedish in-patients at a gynaecological, a medical, an orthopaedic, and a surgical department. The median age was 59 years and 55% of the patients were women. Data were collected using the Quality from the Patient's Perspective (QPP) Questionnaire and the Sense of Coherence Questionnaire. The QPP consists of 61 items designed to measure the following four quality dimensions: the medical-technical competence and the degree of identity-orientation in the actions of the caregivers, the physical-technical conditions and the socio-cultural atmosphere of the care organization. Each question is posed in two different ways in the QPP; one measures perceived reality of the item in question and one the subjective importance the patient ascribes to it. Results showed that patients' ratings of perceived reality covaried systematically with their sense of coherence. This was particularly the case on questions rated by experts to be more abstract and emotionally loaded. Patients' ratings of the subjective importance of the items were weakly related to their sense of coherence. The results are discussed in terms of negative affectivity and culturally shared ideals regarding quality of care.
AIM: This study set out to explore gender differences among medical and surgical acute care inpatients regarding their perceptions of actual care conditions as well as their evaluation of the subjective importance of various care conditions. BACKGROUND: Firstly, the literature reports inconsistent findings regarding male and female patients' views on care. Secondly, the instruments used in most previous research are not derived from a patient perspective. METHODS: The sample consisted of 831 patients (48% were women and 52% were men) at two Swedish hospitals. Data were collected using the questionnaire 'Quality from the Patient's Perspective'. FINDINGS: Male and female patients tended to evaluate the actual care received similarly. However, women tend to assign the different care aspects higher subjective importance. CONCLUSION: More research is needed to illuminate the reasons why men and women hold these different values. Until these issues are better understood, there is no valid basis on a group (gender) level to give specific practical recommendations to nursing managers.
AIM: This study compared elderly patients' reported experiences of pain and distress with enrolled nurses' assessments and related potential differences to patient and enrolled nurse characteristics. BACKGROUND: Many elderly suffer from chronic pain but few studies have focused on this group of patients. METHODS: Data were collected through personal interviews with 38 patients and questionnaires completed by 38 enrolled nurses. FINDINGS: Enrolled nurses underestimated patients' experiences of physical pain, physical discomfort, breathing problems, resignation, and dependency. Pain and distress were overestimated by enrolled nurses who had lower scores on three of the five personality scales used. In contrast, enrolled nurses who had higher scores on these personality scales tended to underestimate the patients' pain and distress. CONCLUSIONS: There is a need to develop staff training programmes in order to optimize the care for elderly patients with chronic pain in the community.
Chronic pain represents a major health problem among older people. The aims of the present study were to: (i) identify various profiles of pain and distress experiences among older patients; and (ii) compare whether background variables, sense of coherence, functional ability and experiences of interventions aimed at reducing pain and distress varied among the patient profiles. Interviews were carried out with 42 older patients. A cluster analysis yielded three clusters, each representing a different profile of patients. Case illustrations are provided for each profile. There were no differences between the clusters, regarding intensity and duration of pain. One profile, with subjects of advanced age, showed a decreased functional ability and favourable scores in most of the categories of pain and distress. Another profile of patients showed favourable mean scores in all categories. The third cluster of patients showed unfavourable scores in most categories of pain and distress. There appears to be a need to treat the three groups of patients in different ways in the caring situation.
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Health-related quality of life (HRQOL) (EORTC QLQ-C30) and levels of anxiety and depression (HADS) were investigated in patients with endocrine tumours of the gastrointestinal tract treated with interferon and/or a somatostatin analogue. In addition, patient perceptions of the importance of and satisfaction with some HRQOL aspects were studied. QOL was perceived as quite good, but more than half of the patients reported diarrhoea. The levels of anxiety and depression were low. Patients perceived physical HRQOL aspects as most important for a good QOL and stated the highest satisfaction with some social aspects. Patients who reported high levels of anxiety or depression were less satisfied with several HRQOL aspects, had more health problems, and a lower level of functioning on several of the EORTC QLQ-C30 scales and single items. Neither demographic nor medical background variables seemed to have an influence on the results. The relatively high QOL could be explained by the fact that most patients had had their treatment for a long period and thus had time to adjust to the situation.
BACKGROUND: This study was undertaken to investigate the safety and effect of DiHA, dextranomers in hyaluronan, a new biocompatible material for endoscopic treatment of stress incontinence, and to further develop the injection technique. METHODS: Twenty women aged 38 to 90 years with genuine stress incontinence participated. Seventeen were followed for a minimum of 6 months after treatment and three for a minimum of 3 months. The DiHA implants were administrered by transurethral endoscopically controlled submucosal injections under local anesthesia. Safety was assessed mainly in terms of infection, need for catheterization, residual urine and dysuria. The treatment efficacy was estimated objectively by a short-term pad test with standardized physical exercise and a 48 h pad-test, 7 days, and 1, 3 and 6 months after treatment. The patient's subjective experience of the effect was also studied. RESULTS: The implantation procedure was well accepted by the patients. Four patients required catheterization due to voiding problems during the first 24 postoperative hours. One patient had urinary retention 14 days postoperatively. No UTI or local infection was detected. Some patients had transient urgency. In 17 or 20 patients the treatment resulted in objective cure or improvement. CONCLUSIONS: This substance shows promising qualities for endoscopic treatment of stress incontinence.
The aim of this study was to explore postoperative experiences of pain and distress in elderly patients, as well as interventions aimed at reducing these conditions, on three occasions. The study group was composed of 100 patients who had undergone elective surgery in two orthopedic and two general surgical units. Of the 50 patients in the orthopedic units, 26 had undergone hip arthroplasty and 24 knee arthroplasty: of the 50 patients in the general surgical units, 23 had had breast cancer surgery, and 27 abdominal surgery. The patients were interviewed, using a structured interview format, on three occasions; at the ward on the first and second day after surgery, and by telephone about ten days after discharge from hospital. Within both the sensory and the emotional dimensions, logistic regression analyses showed that the dependent variables of pain and distress were significantly related above all to type of surgery and sense of coherence (SOC). In a cluster analysis, three meaningful clusters of patients were obtained. The patients in the different profiles showed variations in their experiences of pain and distress. The 12 patients with the least favorable scores had weaker SOC than the patients in the other profiles. It is concluded that type of surgery and psychological factors influenced patients' experiences of pain and distress after undergoing surgery. These experiences should be reduced by identifying risk patients, and improving assistance and support in the nursing ward, and also when patients have returned home.
The aim of the study was to develop a theoretical understanding of conditions and mechanisms affecting experiences of the quality of emotional debriefings, using a grounded theory approach. Twenty interviews were conducted with experienced male debriefing leaders and participants in the Stockholm fire brigade and the Swedish armored United Nations battalions serving in Bosnia. Data were analyzed according to the constant comparative method. A model was formulated according to which the quality of debriefings is formed by the dynamic interplay between group and debriefing leader characteristics. The key group and debriefing leader quality is security. Furthermore, individual group member resourcefulness and vulnerability, together with the degree of knowledge and support from the management of the organization, also affect experiences of the quality of debriefings. The model is discussed in relation to existing thoughts on potentially favorable mechanisms.