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Lise Pedersen

Publications and source records attributed to Lise Pedersen.

14 recordsLinked to original sources

Controlling electron transfer in Acyl-CoA oxidases and dehydrogenases: a structural view.

Plants produce a unique peroxisomal short chain-specific acyl-CoA oxidase (ACX4) for beta-oxidation of lipids. The short chain-specific oxidase has little resemblance to other peroxisomal acyl-CoA oxidases but has an approximately 30% sequence identity to mitochondrial acyl-CoA dehydrogenases. Two biochemical features have been linked to structural properties by comparing the structures of short chain-specific Arabidopsis thaliana ACX4 with and without a substrate analogue bound in the active site to known acyl-CoA oxidases and dehydrogenase structures: (i) a solvent-accessible acyl binding pocket is not required for oxygen reactivity, and (ii) the oligomeric state plays a role in substrate pocket architecture but is not linked to oxygen reactivity. The structures indicate that the acyl-CoA oxidases may encapsulate the electrons for transfer to molecular oxygen by blocking the dehydrogenase substrate interaction site with structural extensions. A small binding pocket observed adjoining the flavin adenine dinucleotide N5 and C4a atoms could increase the number of productive encounters between flavin adenine dinucleotide and O2.

Acyl-CoA Dehydrogenase↗

Assessing health-related quality of life in palliative care: comparing patient and physician assessments.

It is often difficult to recruit patients for palliative care studies and severe attrition must be expected resulting in biased findings. This may be avoided if equivalent information could be obtained from sources other than the patients. Therefore, we investigated whether physician assessments can be used to evaluate the patients' health-related quality of life (HRQOL). Patient and physician assessments of the patients' HRQOL were obtained once a week for up to 13 weeks using EORTC QLQ-C30 items. The agreement between patients and physicians at first contact (N=115) and for the following 13 weeks combined (total N=263) was investigated. Significant differences between patient and physician assessments were observed for all HRQOL domains assessed. Physicians reported patients to have fewer problems/symptoms than patients did for all HRQOL domains except for physical and social functioning. The agreement between patients and physicians was poor. Using physician assessments may bias findings and cannot be recommended as a substitute for patient self-assessment in palliative care.

Adult↗

Symptom priority and course of symptomatology in specialized palliative care.

The study aim was to explore which symptoms/problems cancer patients in palliative care consider most distressing, and to investigate how prioritization at first contact was associated with patient-assessed symptom intensity and change in intensity over time. Initially, 175 patients named and prioritized their five most distressing symptoms. Weekly, they completed the following self-assessment questionnaires: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, Edmonton Symptom Assessment System, and the Hospital Anxiety and Depression Scale. Initial symptom intensity scores and weekly changes were calculated and compared with prioritization of the same symptom. Pain, fatigue, physical function, appetite, nausea/vomiting, dyspnea, and depression were the symptoms most often prioritized. Priority was associated with initial scoring of pain, appetite, nausea/vomiting, dyspnea, constipation, depression, and anxiety, but not with fatigue, physical function, role function, or inactivity. Priority was associated with change in symptom intensity for pain, reduced appetite, nausea/vomiting, and constipation. Symptom prioritization may be a useful guide to choice of treatment as well as to longitudinal symptom evaluation.

Adult↗

Multidimensional measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory.

To investigate the level, dimensionality, and correlates associated with fatigue in patients receiving specialist palliative care, 278 advanced cancer patients referred to a department of palliative medicine during a 2-year period were asked to complete the Multidimensional Fatigue Inventory (MFI-20), a self-assessment questionnaire measuring five dimensions of fatigue, and the Hospital Anxiety and Depression Scale. Of 267 eligible patients, 130 (49%) participated. Mean fatigue scores (0-100 scale) were very high, especially for general fatigue (81), physical fatigue (87), and reduced activity (85). Only some of the MFI-20 subscales were significantly correlated. Fatigue was not correlated with sociodemographic factors. Depressed patients had higher scores on all five subscales except physical fatigue. Anxious patients had higher levels on the mental fatigue subscale only. The variation in fatigue explained by depression varied markedly (4%-31%) among subscales. Fatigue levels were very high in this population. The lack of significant correlation between some subscales indicates that they measure different aspects of fatigue. This is also supported by the differences in associations between fatigue subscales and depression and anxiety.

Adult↗

A longitudinal study of palliative care: patient-evaluated outcome and impact of attrition.

BACKGROUND: The current article evaluated the course of patient-assessed symptomatology in specialized palliative care and tested for bias due to patient attrition in measures of initial symptomatology and treatment outcome. METHODS: Over 2 years, 267 consecutive, eligible patients were referred to a department of palliative care. Upon arrival, 201 patients consented to participate in a questionnaire-based evaluation of quality of life (QOL). Of these, 175 patients participated, and 142, 119, and 95 participated in the study at 1, 2, and 3 weeks, respectively. Weekly, participants completed the self-assessment questionnaires European Organization for Research and Treatment of Cancer QLQ-C30, Edmonton Symptom Assessment System, Hospital Anxiety and Depression Scale, and Multidimensional Fatigue Inventory. Physicians used the Mini Mental State Examination to evaluate cognitive function. Changes from the initial symptom scores for each week were calculated. Initial scoring and change after 1 week were tested for association with completion level, i.e., whether the patient completed questions at 1, 2, 3, or 4 time points. RESULTS: High initial symptom intensity and significant improvements over time were observed for pain, lack of appetite, nausea/vomiting, sleeplessness, constipation, and overall QOL/well-being. For some symptoms, initial scores were significantly higher in patients who dropped out, but the changes over the first week were not significantly different between completion levels for any symptom. CONCLUSIONS: Improvement in symptom intensity was identified. Dropout was associated with higher initial symptomatology but not with poorer outcome of palliative treatment.

Adult↗

Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key enzyme in plant lipid metabolism.

The peroxisomal acyl-CoA oxidase family plays an essential role in lipid metabolism by catalyzing the conversion of acyl-CoA into trans-2-enoyl-CoA during fatty acid beta-oxidation. Here, we report the X-ray structure of the FAD-containing Arabidopsis thaliana acyl-CoA oxidase 1 (ACX1), the first three-dimensional structure of a plant acyl-CoA oxidase. Like other acyl-CoA oxidases, the enzyme is a dimer and it has a fold resembling that of mammalian acyl-CoA oxidase. A comparative analysis including mammalian acyl-CoA oxidase and the related tetrameric mitochondrial acyl-CoA dehydrogenases reveals a substrate-binding architecture that explains the observed preference for long-chained, mono-unsaturated substrates in ACX1. Two anions are found at the ACX1 dimer interface and for the first time the presence of a disulfide bridge in a peroxisomal protein has been observed. The functional differences between the peroxisomal acyl-CoA oxidases and the mitochondrial acyl-CoA dehydrogenases are attributed to structural differences in the FAD environments.

Acyl-CoA Oxidase↗

Expression, purification and crystallization of two peroxisomal acyl-CoA oxidases from Arabidopsis thaliana.

Two members of the acyl-CoA oxidase family from Arabidopsis thaliana have been cloned, overexpressed, purified and crystallized. Long-chain-specific acyl-CoA oxidase 1 crystals are characterized by a large variation in diffraction quality and non-isomorphous unit-cell parameters. The best crystals diffract to 2.0 angstrom using synchrotron radiation, have unit-cell parameters a = 85.2, b = 117.0, c = 131.0 angstrom, alpha = beta = gamma = 90 degrees and show P2(1)2(1)2(1) symmetry. There are two polypeptide chains in the asymmetric unit. Short-chain-specific acyl-CoA oxidase 4 crystals are trigonal, space group P3(1)21/P3(2)21, with unit-cell parameters a = b = 198.7, c = 149.6 angstroms. The crystals are most likely to contain six polypeptide chains in the asymmetric unit. Freshly prepared acyl-CoA oxidase 4 crystals diffract to 3.9 angstroms at cryogenic temperature at beamline I711, Max-Lab, but the diffraction quality degenerates after storage for only a few days in the crystallization drop. A selenomethionine-substituted form of the protein was produced and two-wavelength MAD data were collected at beamline BW7A, EMBL Outstation, Hamburg.

Acyl-CoA Oxidase↗

Pain characteristics and treatment outcome for advanced cancer patients during the first week of specialized palliative care.

To examine pain in cancer patients referred for specialized palliative care, we described pain characteristics and medication on admission, examined changes in pain during the first week, and searched for predictors of initial pain intensity and treatment outcome. On arrival in the department (T0) and after one week (T1), pain was evaluated with the Edmonton Symptom Assessment System (ESAS) and EORTC QLQ-C30. Analgesics were recorded. We investigated the associations between initial pain scores as well as differences from T0 to T1, and clinical and sociodemographic parameters, initial medication, and medical interventions. Of 267 eligible patients, initial pain scores were obtained from 175. Initial pain scores were high, although 81% of patients received opioid treatment at T0. Bone metastases, neuropathic pain, mixed pain pathophysiology, and breakthrough pain were associated with higher initial pain scores. Pain scores decreased during the first week. No single parameter convincingly predicted a better or worse outcome of pain treatment.

Adult↗

Self-assessment in cancer patients referred to palliative care: a study of feasibility and symptom epidemiology.

BACKGROUND: Research in palliative care is considered difficult due to the poor health of patients. However, patient-provided data are essential for a thorough description of patient symptomatology and for the evaluation of care. METHODS: The authors examined the feasibility of a questionnaire-based study using the European Organization for Research and Treatment of Cancer quality-of-life instrument EORTC QLQ-C30, the Edmonton Symptom Assessment System (ESAS), and the Hospital Anxiety and Depression Scale (HADS) in cancer patients who were receiving palliative care. This report describes the symptomatology of participating patients and examines differences in symptomatology between patients in three palliative care functions: inpatient, outpatient, and palliative home care. RESULTS: Of 267 eligible patients who were referred to a department of palliative medicine, initial self-assessment questionnaires were obtained from 176 patients (65.9%). The 91 nonparticipants were older and had lower Karnofsky Performance status (KPS) values than the participants. Almost all participating patients suffered from impaired role function and physical function and had high levels of pain, fatigue, and other symptoms. According to the HADS, 47% of patients suffered from depression. Outpatients had better scores than inpatients and patients in palliative home care for physical function, role function, cognitive function, depression, and inactivity. CONCLUSIONS: It is possible to carry out a questionnaire-based study of symptomatology in consecutive cancer patients in palliative care, achieving rather complete data from the participants. The symptomatology in these patients was very pronounced. The questionnaires were able to detect clinically important differences between places of service.

Adult↗