| 1. |
- Warfvinge, Carl Fredrik, et al.
(författare)
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Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [ 177 Lu]Lu-DOTATATE
- 2024
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Ingår i: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667. ; 65:7, s. 1070-1075
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Tidskriftsartikel (refereegranskat)abstract
- Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor -absorbed dose and tumor response in a cohort of patients with NETs treated with [ 177 Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [1 77 Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [ 177 Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm 3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor -absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.
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| 2. |
- Gunnbjornsdottir, M. I., et al.
(författare)
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Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms
- 2004
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Ingår i: Eur Respir J. - : European Respiratory Society (ERS). ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.
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| 3. |
- Kogevinas, Manolis, et al.
(författare)
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Exposure to substances in the workplace and new-onset asthma : an international prospective population-based study (ECRHS-II)
- 2007
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 370:9584, s. 336-341
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Tidskriftsartikel (refereegranskat)abstract
- Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.
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| 4. |
- Olsson, Caroline, 1970, et al.
(författare)
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Initial experience with introducing national guidelines for CT- and MRI-based delineation of organs at risk in radiotherapy
- 2019
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 11, s. 88-91
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental problem in radiotherapy is the variation of organ at risk (OAR) volumes. Here we present our initial experience in engaging a large Radiation Oncology (RO) community to agree on national guidelines for OAR delineations. Our project builds on associated standardization initiatives and invites professionals from all radiotherapy departments nationwide. Presently, one guideline (rectum) has successfully been agreed on by a majority vote. Reaching out to all relevant parties in a timely manner and motivating funding agencies to support the work represented early challenges. Population-based data and a scalable methodological approach are major strengths of the proposed strategy.
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| 5. |
- Tjellström, Henrik, 1974, et al.
(författare)
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Lipid asymmetry in plant plasma membranes : phosphate deficiency-induced phospholipid replacement is restricted to the cytosolic leaflet
- 2010
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 24:4, s. 1128-1138
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Tidskriftsartikel (refereegranskat)abstract
- As in other eukaryotes, plant plasma membranes contain sphingolipids, phospholipids, and free sterols. In addition, plant plasma membranes also contain sterol derivatives and usually <5 mol% of a galactolipid, digalactosyldiacylglycerol (DGDG). We earlier reported that compared to fully fertilized oats (Avena sativa), oats cultivated without phosphate replaced up to 70 mol% of the root plasma membrane phospholipids with DGDG. Here, we investigated the implications of a high DGDG content on membrane properties. The phospholipid-to-DGDG replacement almost exclusively occurred in the cytosolic leaflet, where DGDG constituted up to one-third of the lipids. In the apoplastic (exoplasmic) leaflet, as well as in rafts, phospholipids were not replaced by DGDG, but by acylated sterol glycosides. Liposome studies revealed that the chain ordering in free sterol/phospholipid mixtures clearly decreased when > 5mol% DGDG was included. As both the apoplastic plasma membrane leaflet (probably the major water permeability barrier) and rafts both contain only trace amounts of DGDG, we conclude that this lipid class is not compatible with membrane functions requiring a high degree of lipid order. By not replacing phospholipids site specifically with DGDG, negative functional effects of this lipid in the plasma membrane are avoided.
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