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| 3. |
- Susek, KH, et al.
(author)
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Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy
- 2023
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In: Cancer immunology, immunotherapy : CII. - : Springer Science and Business Media LLC. - 1432-0851 .- 0340-7004. ; 72:5, s. 1153-1167
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated in clinical trials, the clinical impact of NK cells on the PD1 cascade is less well understood compared to T cells. Furthermore, while NK cells have effector activity within the TME, under continuous ligand exposure, NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. Due to above-mentioned factors, we designed novel NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3ζ to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PD-L1+ target cells. Additionally, PD1-CSR+ NK cells infiltrated and killed tumor spheroids. While primary NK cells (pNK), expressing native PD1, showed decreased degranulation and cytokine production against PD-L1+ target cells by twofold, PD1-CSR+ pNK cells demonstrated increased activity upon PD-L1+ target cell recognition and enhanced antibody-dependent cellular cytotoxicity. PD1-CSR+ pNK cells from patients with MM increased degranulation and cytokine expression against autologous CD138+PD-L1+ malignant plasma cells. Taken together, the present results demonstrate that PD1-CSR+ NK cells enhance and sustain potent anti-tumor activity in a PD-L1+ microenvironment and thus represent a promising strategy to advance adoptive NK cell-based immunotherapies toward PD-L1+ cancers.
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- Chrobok, M, et al.
(author)
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Functional Assessment for Clinical Use of Serum-Free Adapted NK-92 Cells
- 2019
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In: Cancers. - : MDPI AG. - 2072-6694. ; 11:1
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Journal article (peer-reviewed)abstract
- Natural killer (NK) cells stand out as promising candidates for cellular immunotherapy due to their capacity to kill malignant cells. However, the therapeutic use of NK cells is often dependent on cell expansion and activation with considerable amounts of serum and exogenous cytokines. We aimed to develop an expansion protocol for NK-92 cells in an effort to generate a cost-efficient, xeno-free, clinical grade manufactured master cell line for therapeutic applications. By making functional assays with NK-92 cells cultured under serum-free conditions (NK-92SF) and comparing to serum-supplemented NK-92 cells (NK-92S) we did not observe significant alterations in the viability, proliferation, receptor expression levels, or in perforin and granzyme levels. Interestingly, even though NK-92SF cells displayed decreased degranulation and cytotoxicity against tumor cells in vitro, the degranulation capacity was recovered after overnight incubation with 20% serum in the medium. Moreover, lentiviral vector-based genetic modification efficiency of NK-92SF cells was comparable with NK-92S cells. The application of similar strategies can be useful in reducing the costs of manufacturing cells for clinical use and can help us understand and implement strategies towards chemically defined expansion and genetic modification protocols.
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- Adermark, Louise, 1974, et al.
(author)
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Prospective association between use of electronic cigarettes and use of conventional cigarettes: a systematic review and meta-analysis
- 2021
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In: Erj Open Research. - Sheffield : European Respiratory Society (ERS). - 2312-0541. ; 7:3
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Journal article (peer-reviewed)abstract
- Objective The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking. Data sources A systematic literature search was finalised on 11 November 2019 using PubMed (including MEDLINE), EMBASE, Cochrane Library, Scopus, PubMed Health, NICE Evidence Search, PROSPERO, CRD and PsycInfo. Study selection Studies were included if meeting the following criteria: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; allowing for the comparison between users and nonusers of e-cigarettes. Studies rated as having high risk of bias were excluded. Studies were independently assessed by at least two authors. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE. Data synthesis 30 longitudinal studies from 22 different cohorts assessing e-cigarette use among nonsmokers or never-smokers at baseline, and subsequent use of cigarette smoking at follow-up, were included in this review. A random-effects meta-analysis based on 89076 participants showed a pooled unadjusted odds ratio (OR) of cigarette smoking among baseline nonsmoker e-cigarette users compared with nonusers of 4.68 (CI 3.64-6.02), while the adjusted OR was 3.37 (CI 2.68-4.24). These results were consistent irrespective of whether the outcome was measured as ever-smoking or as past 30-day smoking. The evidence was graded as moderate. Conclusions Use of e-cigarettes may predict the initiation or recurrence of cigarette smoking.
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| 22. |
- Alici, E, et al.
(author)
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Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components
- 2008
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:6, s. 3155-3162
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)–compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
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| 24. |
- Barkholt, L, et al.
(author)
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Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study
- 2009
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In: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 1:5, s. 753-764
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Journal article (peer-reviewed)abstract
- The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum α-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
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| 25. |
- Blom Kemdal, Anna, et al.
(author)
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Attributioner och demokratiska dygder
- 2003
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In: Demokratins mekanismer. - 914707275X ; , s. 305-322
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Book chapter (other academic/artistic)abstract
- Statsvetenskaplig forskning visar att demokratiska dygder, som delaktighet, kritiskt tänkande och solidaritet värderas högt av svenska medborgar. Medborgarna anser att de själva kommer ganska nära sitt ideal när det gäller att bete sig i enlighet med dygderna. Man tycker alltså att man själv ”lever som man lär”. Däremot anser de inte att andra människor lever upp till de demokratiska idealen lika bra som de själva gör. Dessa resultat förklaras i kapitlet utifrån psykologisk forskning om kausala attributioner, d v s människors förklaringar till egna och andras beteenden. Kausala attributioner styrs av perspektiv, d v s om man ska förklara sitt eget eller andra människors beteende. Man förklarar eget positivt beteende mer med inre faktorer, såsom personlighetsdrag eller intelligens, och eget negativt beteende med yttre omständigheter som brist på tid eller dåligt väder, medan andra människors både positiva och negativa beteenden överlag förklaras med inre faktorer. Därför kan egna ”odygdiga” beteenden, t.ex. fusk med skatten, bortförklaras med yttre faktorer som att skattemyndigheten är dålig på att informera om hur man ska fylla i deklarationen, medan andras odygdiga beteende ses som ett tecken på att de inte värderar dessa dygder lika högt som man själv gör.
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| 26. |
- Bäck, Emma, et al.
(author)
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The role of issue importance in biased biases regarding the origins of preferences
- 2008
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In: Annual Meeting of the Society for Personality and Social Psychology, Albuquerque, 2008.
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Conference paper (pop. science, debate, etc.)abstract
- Important issues seem to elicit attributional biases regarding origins of attitudes, such that people holding the same attitude as oneself (ingroup) is seen as more rational and less externally influenced than people holding an opposing attitude (outgroup) (Kenworthy & Miller, 2002). The current research examines the role of issue importance for such biases in three studies. In Study 1, students read about pros and cons of prohibiting religious symbols in Swedish schools. They stated their preferred alternative, issue importance, and rated origins of preferences for the ingroup and outgroup. Issue importance was related to biases. This relation was tested in two follow-up studies where high school students read about a hypothetical decision situation where their school was to decide whether to prohibit religious symbols or not. In both studies, participants stated preferred decision alternative and issue importance. Decision outcome was manipulated to concord or discord with participants’ preferences. In Study 2, decision-making form varied so the decision was made by the student council, school authorities or by voting. In Study 3, the student council of participants’ own and an adjacent school were going to make the decision together. School size and composition principle of the student council varied. Results showed that biases varied with target group and issue importance in both studies. In Study 2, biases also varied with decision-making form and outcome, although this was not replicated in Study 3. Importance seems to be decisive for biases, and decision-making form and outcome may under some circumstances influence biases.
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| 29. |
- Diamant, Ulla-Britt, 1955-
(author)
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Long QT syndrome : studies of diagnostic methods
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Background: The Long QT Syndrome (LQTS) is a hereditary heart disease with risk of malignant ventricular arrhythmia and sudden cardiac death. Despite our increased knowledge about genotype and phenotype correlation we still rely on the 12-lead ECG for assessment of the QT interval and the T-wave morphology for diagnosis and risk stratification. Intra- and -inter individual variability in manually QT measurement and, e.g., difficulties in defining the end of the T-wave may impair the diagnosis of LQTS. Increased heterogeneity in ventricular repolarization (VR) may be an important factor in the arrhythmogenicity in cases of LQTS. In a LQTS founder population the same mutation is carried by numerous individuals in many families which provide a unique opportunity to study diagnostic methods, risk assessment, VR and the correlation between genotype and phenotype.Methods: Resting 12-lead ECG and vectorcardiogram (VCG) were recorded in 134 LQTS mutation carriers and 121 healthy controls, to investigate the capability and precision in measuring the QT interval. For assessment of the VR, VCG was compared in individuals with mutations in the KCNQ1 and KCNH2 gene. Genealogical and geographic studies were performed in 37 index cases and their relatives to determine if Swedish carriers of the Y111C mutation in the KCNQ1 gene constitute a founder population. To confirm kinship, haplotype analysis was performed in 26 of the 37 index cases. The age and prevalence of the Y111C mutation were calculated in families sharing a common haplotype.Results: VCG by automatic measurement of the QT interval provided the best combination of sensitivity (90%) and specificity (89%) in the diagnosis of LQTS. VCG showed no consistent pattern of increased VR heterogeneity among KCNQ1 and KCNH2 mutation carriers. Living carriers of the Y111C mutation shared a common genetic (haplotype), genealogic and geographic origin. The age of the Y111C mutation was approximately 600 years. The prevalence of living carriers of the Y111C mutation in the mid-northern Sweden was estimated to 1:1,500-3,000.Conclusion: We have shown that VCG provides a valuable contribution to the diagnosis and risk assessment of LQTS in adults and children. No consistent pattern of increased VR heterogeneity was found among the LQTS mutation carriers. The identified Swedish LQTS founder population will be a valuable source to future LQTS research and may contribute to increase our understanding of LQTS and the correlation of phenotype, genotype and modifying factors.
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| 30. |
- Gilljam, Britt-Mari, 1957-
(author)
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Barns delaktighet i pediatrisk vård – perspektiv, erfarenheter och möjligheter till förändring utifrån barn med långvarig sjukdom
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Bakgrund: Det senaste decenniet har patientens delaktighet fått en allt större uppmärksamhet i forskning, riktlinjer, lagar och klinisk vård. Men många barn känner sig inte delaktiga i sin vård. Vårdpersonal och föräldrar talar ofta över huvudet på barn och ofta förstår barnen inte vad de vuxna pratar om. Barn har också svårt att själva uttrycka sig verbalt i vårdsituationer. Det saknas studier som undersöker långvarigt sjuka barns perspektiv på främjande faktorer för barns delaktighet i vården. Det saknas också användarvänliga svenska validerade verktyg och frågeformulär där barn självständigt kan uttrycka sig och interagera med vårdpersonal, för att mäta barns delaktighet och för att tillämpa delaktighet praktiskt i vården. Både patientlagen och lagen om Förenta nationernas barnkonvention deklarerar att alla barn har rätt att vara delaktiga i sin vård. Denna rättighet behöver överföras till praktisk handling och både vårdpersonal och hälso- och sjukvården som organisation behöver utvecklas.Syfte: Det övergripande syftet med avhandlingen var att utforska barns perspektiv på delaktighet i sin vård, hos barn med långvarig sjukdom och att utveckla och validera verktyg och instrument för att stödja pediatriska verksamheter i tillämpning av barns delaktighet.Metod: I delstudie I användes en konstruktivistisk grundad teori för att utforska barns perspektiv, erfarenheter och önskemål om delaktighet samt främjande faktorer för att öka barns delaktighet. Datainsamlingen skedde genom intervjuer och fokusgrupper med barn med reumatisk sjukdom. I delstudie II användes en konvergent parallell mixad metod för att undersöka om det digitala kommunikationsverktyg Sisom påverkade delaktigheten hos barn med cancer under läkarbesök. I delstudie III användes en participatorisk design där det digitala kommunikationsverktyg Sisom vidareutvecklades och validerades i en svensk kontext. Metoden som användes var iterativ utvärdering genom low- and high-fidelity med friska barn och barn med cancer som deltagare. I delstudie IV användes en instrumentutvecklings design för att utveckla, validera och psykometriskt testa ett frågeformulär om barns delaktighet i vården. I studien deltog friska barn och barn med olika långvariga sjukdomar i utvecklingsarbetet.Resultat: I delstudie I framkom kärnkategorin Att släppa rädsla och osäkerhet öppnar för tillit och delaktighet med Att omges av trygga relationer och miljöer och Att bli stärkt och att få stöd för att kunna vara delaktig som tillhörande koder från den fokuserade kodningen. Dessa koder framkom från med barn med långvarig sjukdom som främjande faktorer för barns delaktighet i vården. Det kvalitativa resultatet i delstudie II visade att barns delaktighet ökade vid användning av det digitala kommunikationsverktyget Sisom. Det kvantitativa resultatet visade att läkarna tilltalade barnen oftare och att barnen talade något mer. I delstudie III utvecklades Sisom, tillsammans med barn, till ett användarvänligt digitalt verktyg på svenska. Verktyget utvecklades från problem fokuserat till salutogenetiskt och påståenden ändrades till frågor. Frågeformuläret (ChiPaC) som utvecklades i delstudie IV resulterade i ett frågeformulär där barn själva kan uttrycka sin uppfattning av delaktighet. Statistiska beräkningar resulterade i en faktoranalys med en fyra-faktorlösning, där 12 frågor inkluderades som förklarade 59,47 % av variansen. De fyra faktorerna benämndes: Att få vara med, Att lita på personalen, Att ta kontroll och Att förstå information. Intra Class Correlation visade stark och måttlig samstämmighet mellan sex av frågorna, svag samstämmighet mellan fem frågor och otillräcklig på en. Chronbach´s alpha beräknades till 0,76. Konklusion: Främjande faktorer för barns delaktighet i sin egen vård vid långvarig sjukdom är trygga relationer och miljöer samt att få stöd i att kunna vara delaktiga. Det digitala kommunikationsverktyget Sisom möjliggör för barn 6–12 år med långvarig sjukdom att självständigt uttrycka sina uppfattningar om hur de mår och sina upplevelser kring sin situation. Sisom främjar också barns delaktighet i form av att de blir lyssnade till, får uttrycka sina åsikter och synpunkter samt får dessa beaktade i samtal med vårdpersonal. Frågeformuläret ChiPaC visade tillfredställande psykometriska egenskaper för att kunna användas vid utvärdering av barns delaktighet i vården. Sisom och ChiPaC utvecklades från barns perspektiv med barn med långvarig sjukdom och friska barn som medaktörer. Denna avhandling bidrar även till kunskap om hur barn med långvarig sjukdom kan engageras som medaktörer i forskning.
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| 31. |
- Gilljam, Britt-Mari, 1957-, et al.
(author)
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Child participation in health care (ChiPaC)—Development and psychometric evaluation of a self‐report instrument for children's participation in health care
- 2020
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In: Journal of Clinical Nursing. - Chichester : Wiley-Blackwell. - 0962-1067 .- 1365-2702. ; 29:1-2, s. 107-118
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Journal article (peer-reviewed)abstract
- Aims and objectives: To develop and evaluate the psychometric properties of a self‐report instrument measuring 6‐ to 12‐year‐old children's own experiences of participation in health care.Background: Validated measures to evaluate children's participation in health care can play a critical role in strategic work towards supporting children's participation at an individual level and in working towards quality improvements at an organisational level. There are, however, no available instruments to achieve this.Methods: An instrument development design was used, together with the TRIPOD checklist. Item construction was based on research about children's perspectives on participation in health care and Shier's model for participation. The face and content validity was evaluated by 14 healthy children, 9 paediatric nurses and 8 children with different diseases. The construct validity, internal consistency and stability reliability were evaluated based on data from 138 children visiting a paediatric clinic.Results: The testing of the face and content validity resulted in an instrument with child‐friendly language, additional instructions and visual attractive presentation. The principle component analysis resulted in the four‐factor solution: “To be included,” “To trust professionals,” “To take control,” and “To understand information.” Internal consistency and intraclass correlation coefficients were acceptable.Conclusion: We conclude that the child participation in health care (ChiPaC) instrument has adequate reliability and validity when used to evaluate children's participation in health care. The involvement of children in the development of ChiPaC resulted in a brief, colourful and user‐friendly instrument for use in paediatric health care.Relevance to clinical practice: This new questionnaire, ChiPaC, is adapted for children between 6–12 years measuring participation in health care from a child perspective. ChiPaC can be used in the practical work of supporting individual children's participation in health care as well as in the strategical work towards quality improvements on an organisational level.What does this paper contribute to the wider global clinical community?The instrument provides a contribution for the practical implementation of the Convention on the Rights of the Child in health care.The high degree of involvement of children in the development of the instrument resulted in a brief, colourful and user‐friendly instrument that can be used in paediatric health care.The instrument can play a critical role in the practical work of supporting individual children's participation in health care as well as in the strategical work of quality improvement on an organisational level.
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| 32. |
- Gilljam, Britt-Mari, 1957-, et al.
(author)
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Impact of an Electronic Health Service on Child Participation in Pediatric Oncology Care : Quasiexperimental Study
- 2020
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In: Journal of Medical Internet Research. - Toronto : J M I R Publications. - 1438-8871. ; 22:7
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Journal article (peer-reviewed)abstract
- Background: There is a shortage of electronic Health (eHealth) services for children 6-12 years old, which promotes their participation in healthcare. Children with long-term diseases want to be more involved in their healthcare, and have the right to receive information, to be listened to, to express their opinions and to participate in decision-making in healthcare.Objective: The aim of this study was to investigate children’s participation during appointments with pediatricians at pediatric oncology clinics, with or without the use of the eHealth service Sisom.Method: A quasi-experimental design with mixed methods was used. Twenty-seven appointments with pediatricians for 14 children aged 6-12 years (mean 8.3) with a cancer diagnosis were filmed and analyzed. The intervention group consisted of children who used an eHealth service prior their appointments with pediatricians at a pediatric oncology clinic and the control group consisted of children during their appointments with pediatricians at four other pediatric oncology clinics. The data from the observations from the films were analyzed with quantitative and qualitative analysis. The quantitative analysis included manual calculations of how many times the pediatricians spoke directly to the children, of the proportion of the appointment time that the children were talking and their levels of participation. The qualitative analysis included directed content analysis included observations of the video films to assess the children´s levels of participation manifested themselves.Results: A greater proportion of what the pediatrician said in the intervention group was addressed to the child than occurred in the control group, but the proportion of the appointment time the children talked was almost the same for both the intervention and the control groups. The levels of participation corresponded to the first three levels of Shier´s participation model: Children were listened to, Children were supported to express their views and Children´s views were taken into account. The results showed an increased level of the children´s participation in the intervention group. Several codes were found about information, which did not fit into any of the existing categories, and a new category was thus formed: Children received information. Situations were also identified where children were actively excluded from participation; these were presented as negative codes.Conclusions: This study shows that the eHealth service Sisom can increase children´s participation during appointments with healthcare professionals. Future research should focus on evaluating outcomes on individual and organizational levels and in different healthcare contexts. © The authors. All rights reserved
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| 34. |
- Gilljam, Karin M, et al.
(author)
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Alginate and nanocellulose dressings with extract from salmon roe reduce inflammation and accelerate healing of porcine burn wounds.
- 2023
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In: Journal of Burn Care & Research. - : Oxford University Press (OUP). - 1559-047X .- 1559-0488. ; 44:5, s. 1140-
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Journal article (peer-reviewed)abstract
- Partial thickness thermal burn wounds are characterized by prolonged inflammatory response, oxidative stress, tissue damage, and secondary necrosis. An optimal dressing for burn wounds would reduce inflammation and oxidative stress while providing a moist, absorbent, and protective cover. We have developed an extract from unfertilized salmon roe containing components with potential anti-inflammatory and antioxidative properties, called HTX. HTX has been combined with alginate from brown algae and nanocellulose from tunicates, and 3D printed into a solid hydrogel wound dressing called Collex. Here, Collex was tested on partial thickness burn wounds in Göttingen minipigs compared to Jelonet, and a variant of Collex without HTX. We found that dermal treatment of burn wounds with Collex resulted in accelerated healing at a majority of measured points over 23 days, compared to treatment with Jelonet. In comparison to Collex without HTX, Collex enhanced healing in the first week after trauma where wound progression was pronounced. Notably, Collex reduced the inflammatory response in the early post-injury phase. The anti-inflammatory response of Collex was investigated in more detail on activated M1 macrophages. We found that Collex, as well as HTX alone, significantly reduced secretion of pro-inflammatory interleukin-1β as well as intracellular levels of oxidative stress. The results from this study indicate that Collex is a potent dressing for treatment of burn wounds, with the anti-inflammatory effect of HTX beneficial in the initial phase, and the moist qualities of the hydrogel favorable both in the initial and the proceeding proliferative phase of wound healing.
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| 35. |
- Gilljam, Marita, 1956, et al.
(author)
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Airway inflammation and infection in congenital bilateral absence of the vas deferens
- 2004
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In: Am J Respir Crit Care Med. ; 169:2
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Journal article (peer-reviewed)abstract
- In cystic fibrosis (CF), airway disease begins early in life. Bacteria and elevated levels of neutrophils and inflammatory mediators have been detected in bronchoalveolar lavage (BAL) fluid from infants with CF. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are common in men with congenital bilateral absence of the vas deferens (CBAVD) and it has been suggested that this syndrome represents a mild form of CF. We hypothesized that men with CBAVD also have subclinical pulmonary disease. Bronchoscopy with BAL, viral and quantitative bacterial cultures, and analyses of total and differential cell count, cytokines, and free neutrophil elastase was performed in eight men with CBAVD, who had mutations in the CFTR and intermediate or elevated sweat chloride levels, and in four healthy control subjects. There was light growth of Staphylococcus aureus in one of eight men with CBAVD, and small numbers of opportunistic gram-negative bacteria in six of eight men with CBAVD and in one control subject. BAL cell counts and neutrophil elastase were within the normal range. Interleukin-8 and tumor necrosis factor-alpha levels were higher for men with CBAVD than for control subjects. These data suggest that mutations in the CFTR in men with CBAVD, in addition to causing infertility, lead to subclinical bacterial pulmonary infection and inflammation consistent with mild CF.
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| 36. |
- Gilljam, Marita, 1956, et al.
(author)
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Clinical Manifestations of Cystic Fibrosis Among Patients With Diagnosis in Adulthood
- 2004
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In: Chest. ; 126:4
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To define the clinical characteristics and diagnostic parameters of patients with cystic fibrosis (CF) diagnosed in adulthood. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS AND METHODS: All patients with a diagnosis of CF made at the Toronto CF Clinics between 1960 and June 2001. Data were collected prospectively and analyzed retrospectively. RESULTS: There were 73 of 1,051 patients (7%) with CF diagnosed in adulthood. Over time, an increasing number and proportion of patients received a diagnosis in adulthood: 27 patients (3%) before 1990, compared to 46 patients (18%) after 1990 (p < 0.001). The mean sweat chloride level was lower for those with CF diagnosed as adults, compared to those with a diagnosis as children (75 +/- 26 mmol/L and 100 +/- 19 mmol/L, respectively; p < 0.001) [mean +/- SD], and adults were more likely to have pancreatic sufficiency (PS) than children (73% vs 13%, respectively; p < 0.0001). In 46 adults who received a diagnosis since 1990, the reason for the initial sweat test was pancreatitis (2 patients, 4%), pulmonary symptoms (18 patients, 39%), pulmonary and GI symptoms (10 patients, 22%), infertility (12 patients, 26%), and genetic screening (4 patients, 9%). Other manifestations were biliary cirrhosis (one patient) and diabetes mellitus (four patients, 9%). The diagnosis could be confirmed by sweat test alone in 30 of 46 patients (65%), by mutation analysis alone in 15 patients (33%), and by a combination in 31 patients (67%). Nasal potential difference (PD) measurements alone confirmed the diagnosis in the remaining 15 patients (33%). CONCLUSION: Patients with CF presenting in adulthood often have PS, inconclusive sweat test results, and a high prevalence of mutations that are not commonly seen in CF diagnosed in childhood. Although most patients have lung disease of variable degrees, single-organ manifestations such as congenital bilateral absence of the vas deferens and pancreatitis are seen. Repeated sweat tests and extensive mutation analysis are often required. Nasal PD may aid the diagnosis, but has not been standardized for clinical diagnosis.
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| 37. |
- Gilljam, Marita, 1956, et al.
(author)
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GI Complications After Lung Transplantation in Patients With Cystic Fibrosis
- 2003
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In: Chest. ; 123:1
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVE: Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. DESIGN: This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. RESULTS: There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). CONCLUSION: GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.
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| 38. |
- GILLJAM, M, et al.
(author)
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INTENSE MINORITIES AND THE PATTERN OF PUBLIC-OPINION
- 1995
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In: INTERNATIONAL JOURNAL OF PUBLIC OPINION RESEARCH. - : Oxford University Press (OUP). - 0954-2892 .- 1471-6909. ; 7:3, s. 199-210
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Journal article (other academic/artistic)
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| 39. |
- Gustafsson, Per M., 1952, et al.
(author)
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Slow and fast lung compartments in cystic fibrosis measured by nitrogen multiple-breath washout.
- 2014
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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 117:7, s. 720-9
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Journal article (peer-reviewed)abstract
- Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis-derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28-18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r(2) = 0.70, P < 0.001) vs. Sacin (r(2) = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.
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| 43. |
- Hedman, Linnea, 1979-, et al.
(author)
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Electronic cigarette use and smoking cessation in cohort studies and randomized trials: A systematic review and meta-analysis
- 2021
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In: Tobacco Prevention & Cessation. - : E.U. European Publishing. - 2459-3087. ; 7
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Journal article (peer-reviewed)abstract
- INTRODUCTION The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent smoking cessation in cohort studies and randomized controlled trials (RCT). METHODS A systematic literature search was finalized 11 November 2019 using EMBASE, Cochrane Library, Scopus, PubMed Health, NICE evidence search, PROSPERO, CRD, PsycInfo, and PubMed including Medline. Inclusion criteria were: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; and allowing for comparison between users and non-users of e-cigarettes. Studies rated as having high risk of bias were excluded. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE. RESULTS Twenty-eight longitudinal, peer-reviewed publications from 26 cohort studies, and eight publications from seven RCTs assessing the association between e-cigarette use and smoking cessation were included in this review. A random-effects meta-analysis based on 39147 participants in cohort studies showed a pooled unadjusted odds ratio (OR) for smoking cessation among baseline e-cigarette users compared with baseline non-users of 0.97 (95% CI: 0.67-1.40), while the adjusted OR was 0.90 (95% CI: 0.63-1.27). The pooled odds ratio for smoking cessation in RCTs was 1.78 (95% CI: 1.41-2.25). The evidence for cohort studies was graded as very low and for RCTs as low. CONCLUSIONS We did not find quality evidence for an association between e-cigarette use and smoking cessation. Although RCTs tended to support a more positive association between e-cigarette use and smoking cessation than the cohort studies, the grading of evidence was consistently low.
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- Meltzer, Carin, et al.
(author)
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Quantification of Pulmonary Pathology in Cystic Fibrosis-Comparison Between Digital Chest Tomosynthesis and Computed Tomography.
- 2021
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In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 195:3-4, s. 434-442
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Journal article (peer-reviewed)abstract
- Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF).DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman's rank correlation coefficient (r) and Krippendorff's alpha (α).The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r=0.82-0.91, P<0.01). Interobserver reliability was high for total score, bronchiectasis and mucus plugging (α=0.83-0.93) in DTS.Chest tomosynthesis could be a low-dose alternative to CT in quantitative estimation of structural lung disease in CF.
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