| 1. |
- Andersson, C, et al.
(author)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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In: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Journal article (peer-reviewed)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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| 2. |
- Brorsson, Caroline, et al.
(author)
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Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes
- 2011
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In: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:2, s. 107-114
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Journal article (peer-reviewed)abstract
- We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect beta-cell function at type 1 diabetes (T ID) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual beta-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1*0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of beta-cell function and HLA-DQB1 genotypes in T1D.
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| 3. |
- Kjellerås, Jennifer, et al.
(author)
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Improved efficacy by using the pTnT-rhtTG plasmid for the detection of celiac disease specific tissue transglutaminase autoantibodies in radioligand binding assays
- 2011
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 71:8, s. 701-704
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Journal article (peer-reviewed)abstract
- Background: Tissue transglutaminase (tTG) autoantibodies are serological markers for celiac disease. The aim was to study the efficacy of the pTnT-rhtTG plasmid and subsequent diagnostic accuracy of tTG autoantibodies for childhood celiac disease using radioligand binding assays.Methods: Coupled in vitro transcription and translation of tTG were performed by pTnT-rhtTG as well as by the pGEMt Easy-rhtTG vectors using the TNT SP6 Coupled Reticulocyte Lysate System in the presence of [(35)S] methionine. Sera from 190 celiac disease children and 74 controls were measured for tTG autoantibodies in two separate radioligand binding assays using anti-human IgA agarose and protein A sepharose beads for the detection of IgA-tTG and IgG-tTG, respectively.Results: Median incorporation of [(35)S] methionine into the pTnT-rhtTG was 26% compared to 16% for the pGEMt Easy-rhtTG plasmid (p = 0.0016). Using pTnT-rhtTG (as compared to pGEMt Easy-rhtTG), sensitivities were IgA-tTG = 96.3% (95.7%) and IgG-tTG = 95.8% (97.3%) and specificities were IgA-tTG = 91.9% (90.5%) and IgG-tTG = 94.6% (98.4%). According to receiver operator characteristics for the pTnT (pGEMt Easy) assays, area under the curves were IgA-tTG = 98.4% (98.4%) and IgG-tTG = 97.7% (97.2%), respectively.Conclusion: The pTnT-rhtTG plasmid increased the efficacy of tTG antigen usage without reducing the diagnostic accuracy of IgA-tTG and IgG-tTG for childhood celiac disease. The pTnT-rhtTG plasmid is therefore recommended over the pGEMt Easy-rhtTG for the assessment of IgA-tTG and IgG-tTG using radioligand binding assays.
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| 4. |
- Grubb, Anders, et al.
(author)
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Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation.
- 2011
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71, s. 145-149
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Journal article (peer-reviewed)abstract
- Abstract Background. The plasma level of cystatin C is a better marker than plasma creatinine for successful aging. It has been assumed that the advantage of cystatin C is not only due to it being a better marker for glomerular filtration rate (GFR) than creatinine, but also because an inflammatory state of a patient induces a raised cystatin C level. However, the observations of an association between cystatin C level and inflammation stem from large cohort studies. The present work concerns the cystatin C levels and degree of inflammation in longitudinal studies of individual subjects without inflammation, who undergo elective surgery. Methods. Cystatin C, creatinine, and the inflammatory markers CRP, serum amyloid A (SAA), haptoglobin and orosomucoid were measured in plasma samples from 35 patients the day before elective surgery and subsequently during seven consecutive days. Results. Twenty patients had CRP-levels below 1 mg/L before surgery and low levels of the additional inflammatory markers. Surgery caused marked inflammation with high peak values of CRP and SAA on the second day after the operation. The cystatin C level did not change significantly during the observation period and did not correlate significantly with the level of any of the four inflammatory markers. The creatinine level was significantly reduced on the first postoperative day but reached the preoperative level towards the end of the observation period. Conclusion. The inflammatory status of a patient does not influence the role of cystatin C as a marker of successful aging, nor of GFR.
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| 5. |
- Gustavsson, Anders, et al.
(author)
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Cost of disorders of the brain in Europe 2010.
- 2011
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In: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
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Journal article (peer-reviewed)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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| 6. |
- Försti, Asta, et al.
(author)
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Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression
- 2010
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In: Genes, Chromosomes and Cancer. - New York : Liss. - 1045-2257 .- 1098-2264. ; 49:3, s. 270-281
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Journal article (peer-reviewed)abstract
- Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.
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| 7. |
- Bengtsson, Mariette, et al.
(author)
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A holistic approach for planning care of patients with irritable bowel syndrome
- 2010
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In: Gastroenterology Nursing. - : Lippincott Williams & Wilkins. - 1042-895X .- 1538-9766. ; 33:2, s. 98-108
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Journal article (peer-reviewed)abstract
- The aims of this study were to determine whether a registered nurse can collect information and plan a holistic and individual strategy for the treatment of patients with irritable bowel syndrome (IBS) and whether this approach can reduce these patients' health aspects. The referrals of 50 Swedish-speaking female patients aged between 18 and 65 years with the preliminary diagnosis of IBS were collected and scrutinized by a gastroenterologist at a university hospital. Of these, 41 patients agreed to participate but 2 did not show up. The 39 patients were randomized into one of two groups: (1) the intervention group (n = 19) where the subjects were interviewed on the basis of the theory of culture care by a nurse before visiting a gastroenterologist and (2) the control group (n = 20) where the subjects first met a gastroenterologist. After the medical examination, 19 subjects were found to have diseases other than IBS. The interview gave a holistic view of the subjects' problems, which could be of use when planning further care. Because subjects sometimes did not receive an accurate diagnosis by their primary care physician, however, the clinic nurse could not give these subjects IBS-specific information because the subjects' diagnosis had not been established. The initial medical assessments based on the primary care doctors' care of many subjects with IBS symptoms were a noted weak point.
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| 8. |
- Jönsson, Peter, et al.
(author)
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Cardiovascular and cortisol reactivity and habituation to a virtual reality version of the Trier Social Stress Test : a pilot study
- 2010
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In: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 35:9, s. 1397-1403
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Journal article (peer-reviewed)abstract
- The Trier Social Stress Test (TSST) is a widely used protocol to induce stress in laboratory settings. Briefly, in the TSST, the test participant is asked to hold a speech and to do an arithmetic task in front of an audience. In the present pilot study, we examined endocrine and autonomic reactivity and habituation to repeated stress provocations using a virtual reality (VR) version of TSST. The VR system was a CAVE™ system with three rear projected walls (4 m×3 m), and one floor projection. The system also included a head tracking system and passive stereoscopy. The virtual audience consisted of one woman, and two men. Ten healthy men, mean age 28.3 years (24-38 years), were confronted with the test twice (1 week between sessions), during which salivary cortisol, heart rate (HR), high frequency heart rate variability (HF-HRV, parasympathetic activity), and T-wave amplitude (TWA, suggested to be related to sympathetic influence on myocardial performance) were assessed. Cortisol secretion showed a marked increase (88% vs. baseline) during the first stress provocation, but habituated in the second session. The magnitude of HR and TWA reactivity during stress provocation was approximately the same at both sessions, implying a stable increase in sympathetic activity. Heart rate showed a maximum increase of 40% at the first session, and 32% at the second. TWA showed a maximum decrease of 42% at the first session, and 39% at the second. The results resemble those obtained in prior studies using the real-life TSST. If these results can be replicated with larger samples, VR technology may be used as a simple and standardized tool for social stress induction in experimental settings.
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| 9. |
- Sjövall, Katarina, et al.
(author)
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Adjuvant radiotherapy of women with breast cancer – information, support and side-effects
- 2010
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In: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 14:2, s. 147-153
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Journal article (peer-reviewed)abstract
- The aim of this study was to 1) examine the occurrence and burden of side effects over time in the period after post surgical adjuvant radiotherapy in women with breast cancer and 2) explore the women's experiences of given information and need of support to handle side effects. Material and method: 171 women with breast cancer receiving post-surgical adjuvant radiotherapy completed a questionnaire on radiotherapy-related side effects (Treatment Toxicity Assessment Tool OTTAT) at four times between the start of radiotherapy and six months after completion. Comparisons were made between women with breast conservative surgery (group A) and women with modified mastectomy (group B), and for having chemotherapy or not (C+ and C-). Questions regarding the experience of delivered information and support were added. Results: Fatigue was the single most prevalent side effect and, together with skin reactions and pain, it also had the highest mean score over the study period and the largest score increase during treatment. The largest increase during the six months was seen for skin reaction, pain, and dyspnoea. The average score for skin reaction was significantly higher in group B than in group A. A majority of the women experienced the given information and support as satisfying and a need for follow-up of the side-effects was expressed. Conclusion: Nursing for women with breast cancer receiving adjuvant radiotherapy should focus on preventing and treating side effects, and also include the period post treatment. There is a need for developing evidence based guidelines including guidelines for follow-up.
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| 10. |
- Sjövall, Katarina, et al.
(author)
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Experiences of living with advanced colorectal cancer from two perspectives - inside and outside
- 2011
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In: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 15:5, s. 390-397
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Journal article (peer-reviewed)abstract
- Purpose: To investigate how life situation by persons with advanced colorectal cancer and their partners is affected by living with the disease and its treatment.Method: Separate, individual interviews were made with persons with advanced colorectal cancer (n = 12) and their partners (n = 9) about how their daily lives were affected by the disease and its treatment. The verbatim were analysed using content analysis.Results: Living with the illness of advanced colorectal cancer was experienced to be: being inside or outside the healthcare system, striving for normality and becoming conscious of life's value and vulnerability. Living as a partner was experienced as living in an altered relation and as living in the shadow of the disease.Conclusions: When one in a partner relation suffers from colorectal cancer, it changes life and life perspective for both partners. Partners need to be invited to and involved in the care. Cancer nursing should focus on supporting the strive for normality in daily life, as the disease and its' treatment may last for a longer period of time. Supporting the partner may benefit the person with cancer as well, to cope along the illness trajectory.
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