| 1. |
- Borg, Sixten, et al.
(författare)
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The cost-effectiveness of treatment with erythropoietin compared to red blood cell transfusions for patients with chemotherapy induced anaemia: a Markov model.
- 2008
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1009-1017
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anaemia is a common complication of chemotherapy. As anaemia can lead to e.g. fatigue, depression, social isolation and chest pain it diminishes physical capacity and quality of life. It is generally accepted that symptomatic anaemia should be corrected. Treatment options include red blood cell transfusion (RBCT), erythropoietin (EPO) administration or a combination of both. OBJECTIVE: The objective of this study was to carry out a cost-effectiveness analysis of treatment with EPO (epoetin alfa), compared to treatment with RBCT for patients with chemotherapy-induced anaemia in Sweden from a health care perspective. METHOD: A model was developed for estimating incremental costs and QALY gains associated with EPO treatment compared to treatment with RBCTs, based on a model commissioned by the UK National Institute for Health and Clinical Excellence and adjusted to reflect Swedish treatment practice. Data regarding patient characteristics, response rates, and RBCT was derived from a Swedish observational study of EPO treatment in cancer patients with chemotherapy related anaemia. Swedish guidelines and unit costs were used throughout the study. A systematic review of EPO for treatment of anaemia associated with cancer was used to estimate QALY gains associated with changes in Hb-concentrations in our model. RESULTS: The model's results validate well to real world data from three major hospitals in Sweden. The cost per QALY gained from administration of EPO was estimated at EUR 24,700 in the base case analysis. Practicing an EPO treatment target Hb-level of 12 g/dl yields a cost per QALY about 40% lower than practicing a Hb-target level of 13 g/dl, which is in agreement with updated recommendations of using a 12 g/dl target. CONCLUSION: The estimated cost per QALY falls well within the range acceptable in Sweden when practicing a Hb-target level of 12 g/dl. The incremental cost of elevating Hb-levels above 13 g/dl is very high in relation to the incremental QALY gain achieved.
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| 2. |
- Bresell, Anders, et al.
(författare)
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Bioinformatic and enzymatic characterization of the MAPEG superfamily
- 2005
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 272:7, s. 1688-1703
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Tidskriftsartikel (refereegranskat)abstract
- The membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily includes structurally related membrane proteins with diverse functions of widespread origin. A total of 136 proteins belonging to the MAPEG superfamily were found in database and genome screenings. The members were found in prokaryotes and eukaryotes, but not in any archaeal organism. Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members, corresponding to the six families of microsomal glutathione transferases (MGST) 1, 2 and 3, leukotriene C4 synthase (LTC4), 5-lipoxygenase activating protein (FLAP), and prostaglandin E synthase. Prokaryotes contain at least two distinct potential ancestral subfamilies, of which one is unique, whereas the other most closely resembles enzymes that belong to the MGST2/FLAP/LTC4 synthase families. The insect members are most similar to MGST1/prostaglandin E synthase. With the new data available, we observe that fish enzymes are present in all six families, showing an early origin for MAPEG family differentiation. Thus, the evolutionary origins and relationships of the MAPEG superfamily can be defined, including distinct sequence patterns characteristic for each of the subfamilies. We have further investigated and functionally characterized representative gene products from Escherichia coli, Synechocystis sp., Arabidopsis thaliana and Drosophila melanogaster, and the fish liver enzyme, purified from pike (Esox lucius). Protein overexpression and enzyme activity analysis demonstrated that all proteins catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione. The E. coli protein displayed glutathione transferase activity of 0.11 µmol·min−1·mg−1 in the membrane fraction from bacteria overexpressing the protein. Partial purification of the Synechocystis sp. protein yielded an enzyme of the expected molecular mass and an N-terminal amino acid sequence that was at least 50% pure, with a specific activity towards 1-chloro-2,4-dinitrobenzene of 11 µmol·min−1·mg−1. Yeast microsomes expressing the Arabidopsis enzyme showed an activity of 0.02 µmol·min−1·mg−1, whereas the Drosophila enzyme expressed in E. coli was highly active at 3.6 µmol·min−1·mg−1. The purified pike enzyme is the most active MGST described so far with a specific activity of 285 µmol·min−1·mg−1. Drosophila and pike enzymes also displayed glutathione peroxidase activity towards cumene hydroperoxide (0.4 and 2.2 µmol·min−1·mg−1, respectively). Glutathione transferase activity can thus be regarded as a common denominator for a majority of MAPEG members throughout the kingdoms of life whereas glutathione peroxidase activity occurs in representatives from the MGST1, 2 and 3 and PGES subfamilies.
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| 3. |
- Bresell, Anders, et al.
(författare)
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Characterization of oligopeptide patterns in large protein sets
- 2007
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 8:346, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent sequencing projects and the growth of sequence data banks enable oligopeptide patterns to be characterized on a genome or kingdom level. Several studies have focused on kingdom or habitat classifications based on the abundance of short peptide patterns. There have also been efforts at local structural prediction based on short sequence motifs. Oligopeptide patterns undoubtedly carry valuable information content. Therefore, it is important to characterize these informational peptide patterns to shed light on possible new applications and the pitfalls implicit in neglecting bias in peptide patterns. Results: We have studied four classes of pentapeptide patterns (designated POP, NEP, ORP and URP) in the kingdoms archaea, bacteria and eukaryotes. POP are highly abundant patterns statistically not expected to exist; NEP are patterns that do not exist but are statistically expected to; ORP are patterns unique to a kingdom; and URP are patterns excluded from a kingdom. We used two data sources: the de facto standard of protein knowledge Swiss-Prot, and a set of 386 completely sequenced genomes. For each class of peptides we looked at the 100 most extreme and found both known and unknown sequence features. Most of the known sequence motifs can be explained on the basis of the protein families from which they originate. Conclusion: We find an inherent bias of certain oligopeptide patterns in naturally occurring proteins that cannot be explained solely on the basis of residue distribution in single proteins, kingdoms or databases. We see three predominant categories of patterns: (i) patterns widespread in a kingdom such as those originating from respiratory chain-associated proteins and translation machinery; (ii) proteins with structurally and/or functionally favored patterns, which have not yet been ascribed this role; (iii) multicopy species-specific retrotransposons, only found in the genome set. These categories will affect the accuracy of sequence pattern algorithms that rely mainly on amino acid residue usage. Methods presented in this paper may be used to discover targets for antibiotics, as we identify numerous examples of kingdom-specific antigens among our peptide classes. The methods may also be useful for detecting coding regions of genes.
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| 4. |
- Brismar, Torkel, et al.
(författare)
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Liver Vessel Enhancement by Gd-BOPTA and Gc-EOB-DTPA – a Comparison in Healthy Volunteers.
- 2009
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Ingår i: Acta Radiologica. - : Informa Healthcare. - 0284-1851 .- 1600-0455. ; 50:7, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- Background: A thorough understanding of magnetic resonance (MR) contrast media dynamics makes it possible to choose the optimal contrast media for each investigation. Differences in visualizing hepatobiliary function between Gd-BOPTA and Gd-EOB-DTPA have previously been demonstrated, but less has been published regarding differences in liver vessel visualization.Purpose: To compare the liver vessel and liver parenchymal enhancement dynamics of Gd-BOPTA (MultiHance®) and Gd-EOB-DTPA (Primovist®). Material and Methods: The signal intensity of the liver parenchyma, the common hepatic artery, the middle hepatic vein, and a segmental branch of the right portal vein, was obtained in 10 healthy volunteers before contrast media administration, during arterial and portal venous phases, and 10, 20, 30, 40 and 130 minutes after intravenous contrast medium injection, but due to scanner limitations not during the hepatic venous phase. Results: Maximum enhancement of liver parenchyma was observed from the portal venous phase until 130 minutes after Gd-BOPTA administration and from 10 minutes to 40 minutes after Gd-EOB-DTPA. There was no difference in maximum enhancement of liver parenchyma between the two contrast media. When using Gd-BOPTA, the vascular contrast enhancement was still apparent 40 minutes after injection, but had vanished 10 minutes after Gd-EOB-DTPA injection. The maximum difference in signal intensity between the vessels and the liver parenchyma was significantly greater with Gd-BOPTA than with Gd-EOB-DTPA (p<0.0001). Conclusion: At the dosage used in this study Gd-BOPTA yields higher maximum enhancement of the hepatic artery, portal vein and middle hepatic vein during the arterial and the portal venous phase and during the delayed phases than Gd-EOB-DTPA does, whereas there is no difference in liver parenchymal enhancement between the two contrast agents.
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| 5. |
- Dahlström, Nils, 1969-, et al.
(författare)
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Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB-DTPA in healthy subjects
- 2007
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Ingår i: Acta Radiologica. - : Informa Healthcare. - 0284-1851 .- 1600-0455. ; 48:4, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the biliary enhancement dynamics of the two gadolinium chelates Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist) in normal healthy subjects. MATERIAL AND METHODS: Ten healthy volunteers were evaluated with both agents by magnetic resonance (MR) imaging at 1.5T using a breath-hold gradient-echo T1-weighted VIBE sequence. The relative signal intensity (SI) differences between the common hepatic duct (CHD) and liver parenchyma were measured before and 10, 20, 30, 40, 130, 240, and 300 min after contrast medium injection. RESULTS: Biliary enhancement was obvious 10 min post-injection for Gd-EOB-DTPA and was noted at 20 min for Gd-BOPTA. At 40 min delay, Gd-BOPTA reached its peak biliary enhancement, but at neither 30 nor 40 min delay was there any significant difference compared with that of Gd-EOB-DTPA. At later delays, the contrast between CHD and liver continued to increase for Gd-EOB-DTPA, whereas it decreased for Gd-BOPTA. CONCLUSION: The earlier onset and longer duration of a high contrast between CHD and liver for Gd-EOB-DTPA facilitates examination of hepatobiliary excretion. Therefore, Gd-EOB-DTPA may provide adequate hepatobiliary imaging within a shorter time span than Gd-BOPTA and facilitate scheduling at the MR unit. Further studies in patients are required to compare the imaging advantages of Gd-EOB-DTPA and Gd-BOPTA in clinical practice.
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| 6. |
- Persson, Anders, et al.
(författare)
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Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta
- 2006
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:2, s. 172-178
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare three methods for standardizing volume rendering technique (VRT) protocols by studying aortic diameter measurements in magnetic resonance angiography (MRA) datasets.Material and Methods: Datasets from 20 patients previously examined with gadolinium-enhanced MRA and with digital subtraction angiography (DSA) for abdominal aortic aneurysm were retrospectively evaluated by three independent readers. The MRA datasets were viewed using VRT with three different standardized transfer functions: the percentile method (Pc-VRT), the maximum-likelihood method (ML-VRT), and the partial range histogram method (PRH-VRT). The aortic diameters obtained with these three methods were compared with freely chosen VRT parameters (F-VRT) and with maximum intensity projection (MIP) concerning inter-reader variability and agreement with the reference method DSA.Results: F-VRT parameters and PRH-VRT gave significantly higher diameter values than DSA, whereas Pc-VRT gave significantly lower values than DSA. The highest interobserver variability was found for F-VRT parameters and MIP, and the lowest for Pc-VRT and PRH-VRT. All standardized VRT methods were significantly superior to both MIP and F-VRT in this respect. The agreement with DSA was best for PRH-VRT, which was the only method with a mean error below 1 mm and which also had the narrowest limits of agreement (95% of cases between 2.1 mm below and 3.1 mm above DSA).Conclusion: All the standardized VRT methods compare favorably with MIP and VRT with freely selected parameters as regards interobserver variability. The partial range histogram method, although systematically overestimating vessel diameters, gives results closest to those of DSA.
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| 7. |
- Persson, Anders, 1953-, et al.
(författare)
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Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease : a retrospective analysis of feasibility and adverse reaction to contrast material
- 2006
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Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundComputed Tomography Cholangiography (CTC) is a fast and widely available alternative technique to visualise hepatobiliary disease in patients with an inconclusive ultrasound when MRI cannot be performed. The method has previously been relatively unknown and sparsely used, due to concerns about adverse reactions and about image quality in patients with impaired hepatic function and thus reduced contrast excretion. In this retrospective study, the feasibility and the frequency of adverse reactions of CTC when using a drip infusion scheme based on bilirubin levels were evaluated.MethodsThe medical records of patients who had undergone upper abdominal spiral CT with subsequent three-dimensional rendering of the biliary tract by means of CTC during seven years were retrospectively reviewed regarding serum bilirubin concentration, adverse reaction and presence of visible contrast media in the bile ducts at CT examination. In total, 153 consecutive examinations in 142 patients were reviewed.ResultsContrast media was observed in the bile ducts at 144 examinations. In 110 examinations, the infusion time had been recorded in the medical records. Among these, 42 examinations had an elevated bilirubin value (>19 umol/L). There were nine patients without contrast excretion; 3 of which had a normal bilirubin value and 6 had an elevated value (25–133 umol/L). Two of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor adverse reaction – a pricking sensation in the face. No other adverse effects were noted.ConclusionWe conclude that drip infusion CTC with an infusion rate of the biliary contrast agent iotroxate governed by the serum bilirubin value is a feasible and safe alternative to MRC in patients with and without impaired biliary excretion.In this retrospective study the feasibility and the frequency of adverse reactions when using a drip infusion scheme based on bilirubin levels has been evaluated.
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| 8. |
- Persson, Anders, 1953-, et al.
(författare)
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Volume rendering of three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease : a retrospective study
- 2005
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 78:936, s. 1078-1085
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the diagnostic potential of prolonged drip infusion CT cholangiography (DIC-CT) using meglumine iotroxate (Biliscopin®) and 3D volume rendering in patients with suspected obstructive biliary disease. From a material of 142 patients who had undergone a drip infusion CT, all cases with a verified surgical or endoscopic retrograde cholangiography (ERC) diagnosis (n=33) were selected. Age-matched controls were selected from the remaining examinations. Three radiologists reviewed all 66 examinations in retrospect, independently as well as in consensus. The image quality and the estimated diagnostic quality were rated as good or moderate in 91% of the 198 reviews. The consensus sensitivity and specificity for diagnosing biliary stones was 88% and 94%, respectively (with sensitivities ranging from 88% to 94% for individual observers, and specificities from 86% to 96%). Two out of three strictures were observed. No false positive strictures were described. The use of volume rendering technique (VRT) improved diagnostic certainty in 28/198 (14%) of the evaluations. The visualization of ductal stones was improved in 18/48 (38%). No differences in diagnostic quality between single and multislice CT were observed. We conclude that a detailed image of the biliary tree with good sensitivity and specificity can be obtained by means of bilirubin-governed infusion time DIC-CT with volume rendering reconstruction.
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| 9. |
- Silins, Ilvars, et al.
(författare)
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Chlamydia trachomatis infection and persistence of human papillomavirus.
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 116:1, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-itern questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection.
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| 10. |
- Wahlstrom, Jan, et al.
(författare)
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Autoimmune T cell responses to antigenic peptides presented by bronchoalveolar lavage cell HLA-DR molecules in sarcoidosis
- 2009
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Ingår i: CLINICAL IMMUNOLOGY. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 133:3, s. 353-363
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of sarcoidosis remains unknown. Recently, by mass spectrometric sequencing of peptides eluted from HLA-DR molecules of bronchoalveolar lavage (BAL) cells from DRB1*0301(pos) patients, we identified potential self-antigens in sarcoidosis. The aim of the present study was to investigate the capacity of selected peptides to stimulate tung and blood T cells of sarcoidosis patients using an interferon-gamma ELISPOT assay. In peripheral blood, there were strong T cell responses to a peptide derived from the cytoskeletal protein vimentin in 6 out of 11 DRBI*0301(pos) patients with active disease but not in patients with other HLA types. BAL T cell responses against peptides derived from ATP synthase or from lysyl-tRNA synthetase were detected in DRB1*0301(pos) as welt as DRB1*0301(neg) patients. By using antigenic peptides presented in vivo in the lungs of sarcoidosis patients, we have identified blood and lung T cell autoimmune responses that may help sustain the inflammation in this disease.
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