| 11. |
- Rosfors, Stefan, et al.
(författare)
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Venous occlusion plethysmography in patients with post-thrombotic venous claudication
- 2013
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 58:3, s. 722-726
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Post-thrombotic venous claudication is a serious condition that may be treated with iliac vein stenting or open surgery, and there is a need for hemodynamic tests in the preoperative evaluation. The purpose of this study was to describe the results of venous occlusion plethysmography in patients with venous claudication and to analyze the outflow curve to find variables that best describe the functional abnormality in this patient group.METHODS: Twenty-nine patients with previous deep venous thrombosis and with clinical evidence of venous claudication were retrospectively identified. The results of venous occlusion plethysmography in these patients were compared with results obtained in a group of 63 healthy control subjects of similar age and sex. Computerized strain-gauge plethysmography was used in a capacitance mode where the occlusion time is determined by an electronic detector allowing the maximal venous volume to be achieved in all limbs. Outflow volumes (OV1, OV4) and outflow fractions (OF1, OF4) were calculated at 1 and 4 seconds after cuff release. Outflow fraction is OV divided by maximal venous volume.RESULTS: Both outflow volumes and outflow fractions were significantly reduced in patients compared with healthy control subjects. Outflow fractions were more sensitive than outflow volumes in identifying patients with venous claudication. The most discriminating variable was OF4 that was reduced below the normal lower limit in 69% of the patients, most severely reduced in patients with severe claudication.CONCLUSIONS: Patients with venous claudication attributable to remaining post-thrombotic iliofemoral obstructive disease are characterized by a functional disturbance shown with venous occlusion plethysmography as a reduced venous outflow during the initial 4 seconds following cuff release in relation to their true maximal venous volume. Our results suggest that venous occlusion plethysmography can be a valuable tool in the preoperative workup for selection of patients with iliofemoral vein obstruction that may benefit from venous intervention.
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| 12. |
- Hammarsten, Ola, et al.
(författare)
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Evaluation of a Sensitive Copeptin Assay for Clinical Measurement
- 2012
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Ingår i: The Open Clinical Chemistry Journal. - : Bentham Science Publishers Ltd.. - 2588-7785 .- 1874-2416. ; 5:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Background: Copeptin, a marker of vasopressin production, has been introduced for earlier diagnosis of acute myocardial infarction and other clinical emergencies. We evaluated the analytical performance of a new generation copeptin assay in an inter-laboratory trial. Methods: Precision, linearity range, carry-over contamination, the limit of blank and an inter-laboratory comparison trial for the copeptin US KRYPTOR assay were performed on the B·R·A·H·M·S KRYPTOR compact PLUS. Results: The intra-assay imprecision (CVs) was 12.6–2.2% and total imprecision over five days was 12.3-4.3% between 3.1 and 18.2 pmol/L. The assay had excellent linearity between 7-222 pmol/L. The limit of blank was 2.5 pmol/L and the limit of detection was 3.2 pmol/L, but was dependent on the analyte-free material used. No significant difference between sample type, such as serum or different types of plasma or reagent lots, was noted. The copeptin results remained unchanged upon five repeated freeze-thaw cycles. A set of patient samples with a mean copeptin concentration of 2.1-61 pmol/L run at two separate sites showed close correlation (r2=0.99, slope=1.01, intercept=0.35), indicating comparable results across laboratories. Conclusion: The new ultrasensitive copeptin KRYPTOR assay shows excellent inter-lab precision, opening up the possibility for international guidelines to exclude acute myocardial infarction.
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| 13. |
- Muslimovic, Aida, et al.
(författare)
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Calibrators for Clinical Measurements of Phosphorylated H2AX in Patient Cells by Flow Cytometry
- 2012
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Ingår i: The Open Clinical Chemistry Journal. - : Bentham Science Publishers Ltd.. - 2588-7785 .- 1874-2416. ; 5:1, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Agents that induce DNA double-strand breaks (DSBs), such as ionizing radiation, are frequently used in cancer therapy. H2AX is rapidly phosphorylated in response to DSBs and serves as a way to measure the extent of DSBs induced in patient cells. We have previously reported a flow cytometry-based method for measuring H2AX phosphorylation in pa-tient cells undergoing radiotherapy. To be able to implement measurement of H2AX phosphorylation in clinical practice, we have characterized calibrators for the flow cytometry analysis based on phosphopeptide-coated beads and fixed cells. The calibrator beads and fixed cells lost less than 11% of the signal after storage for 40 days under optimal conditions and were able to correct for day-to-day variation in method performance.
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| 14. |
- Wahlin, Björn Engelbrekt, et al.
(författare)
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T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
- 2011
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:12, s. 4136-4144
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. EXPERIMENTAL DESIGN: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a-rituximab combinations. RESULTS: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). CONCLUSIONS: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8(+) cells.
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| 15. |
- Hjelmevoll, Stig Ove, et al.
(författare)
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Appropriate Time for Test-of-Cure when Diagnosing Gonorrhoea with a Nucleic Acid Amplification Test
- 2012
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Ingår i: Acta Dermato-Venereologica. - Uppsala : Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 92:3, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- Culture is commonly regarded as the gold standard for diagnosis of Neisseria gonorrhoeae. However, nucleic acid amplification tests (NAATs) have rapidly replaced culture for diagnostics in many settings. The aim of the present study was to investigate the appropriate time for test-of-cure (TOC) when NAATs are used for diagnosis of gonorrhoea. In total, 30 patients (28 men and 2 women) provided urethral, cervical, rectal or pharyngeal specimens for TOC. All included patients, except one who did not return for second TOC before day 19, tested negative within 2 weeks after treatment with cefixime 400 mg x 1. Antimicrobial susceptibility testing showed that 68% of the culture-positive strains were resistant to ciprofloxacin. Thus, the recommended empirical treatment with ciprofloxacin in Norway should be changed immediately. TOC can be performed 2 weeks after treatment when NAATs are used for diagnosis of gonorrhoea.
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| 16. |
- Hoffner, S, et al.
(författare)
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Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience
- 2013
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 17:11, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organizations yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. less thanbrgreater than less thanbrgreater thanOBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. less thanbrgreater than less thanbrgreater thanMETHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. less thanbrgreater than less thanbrgreater thanRESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
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| 17. |
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| 18. |
- Nordström, Lena, et al.
(författare)
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SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma : a Nordic Lymphoma Group study
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 166:1, s. 98-108
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.
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| 19. |
- Hjerpe, Elisabet, et al.
(författare)
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Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.
- 2013
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Ingår i: BMC Clinical Pathology. - : BioMed Central (BMC). - 1472-6890. ; 113:30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A deregulated energy metabolism is a hallmark of malignant disease that offers possible future targets for treatment. We investigated the prognostic value of the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase type M2 (PKM2), mitochondrial β-F1-ATPase (ATP5B) and the bioenergetic cellular (BEC) index in advanced ovarian cancer.METHODS: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 met the eligibility criteria; stage IIC-IV, serous or endometrioid subtype, specimens containing ≥ 50% tumor cells and patients receiving platinum-based chemotherapy. An adequate amount of mRNA could be extracted in all but one case, with a resultant study population of 56 patients. Eighty-six percent of cases had serous tumors, and 93% were grade 2-3. GAPDH, PKM2 and ATP5B mRNA- and protein expression was assessed by real-time PCR and immunohistochemistry. We estimated the association with platinum-free interval (PFI) and overall survival (OS) by Cox proportional hazards models. Median follow-up was 60 months.RESULTS: High GAPDH mRNA levels (HR 2.1, 95% CI 1.0-4.5) and low BEC-index (HR 0.47, 95% CI 0.23-0.95) were both independently associated with shorter PFI. Median PFI for patients with high GAPDH mRNA was 5.0 months compared to 10.1 months for low expression cases (p = 0.031). Similarly, median PFI for patients with low BEC-index based on mRNA was 5.3 months compared to 9.8 months for high BEC-index cases (p = 0.028).CONCLUSIONS: High GAPDH or low BEC-index mRNA expression indicate early disease progression in advanced serous ovarian cancer.
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| 20. |
- Nasir, Waqas, et al.
(författare)
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Lewis histo-blood group alpha1,3/alpha1,4 fucose residues may both mediate binding to GII.4 noroviruses
- 2012
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 22:9, s. 1163-72
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Tidskriftsartikel (refereegranskat)abstract
- Human noroviruses cause recurrent epidemics of gastroenteritis known to be dominated by the clinically important GII.4 genotype which recognizes human Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment factors. There is increasing evidence that GII.4 noroviruses have undergone evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this study, we have investigated the possibilities of the Lewis alpha1,3/alpha1,4 fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study was carried out using molecular dynamics simulations of Lewis type-1 and type-2 chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the computer simulations, we suggest the possibility of two receptor binding modes for Lewis HBGAs: the "Secretor pose" with the Secretor Fucalpha1,2 in the binding site and the "Lewis pose" with the Lewis Fucalpha1,3/alpha1,4 residues in the binding site. This was further supported by an extensive GlyVicinity analysis of the Protein Data Bank with respect to the occurrence of the Lewis and Secretor poses in complexes of Lewis antigens with lectins and antibodies as well as GII norovirus strains. The Lewis pose can also explain the interactions of GII.4 norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model suggests binding of complex branched polysaccharides, with the Lewis antigens at the nonreducing end, to P domain dimers of GII.4 strains. Our results are relevant for understanding the evolution of norovirus binding specificities and for in silico design of future antiviral therapeutics.
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