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Tidefelt, Ulf
Publications (10 of 28) Show all publications
Ahlstrand, E., Bäckman, A., Persson, L., Mölling, P., Tidefelt, U. & Söderquist, B. (2014). Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 122(6), 539-544
Open this publication in new window or tab >>Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
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2014 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed) Published
Abstract [en]

The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
coagulase-negative staphylococci; Staphylococcus epidermidis; hematological malignancy; blood culture contamination
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-32422 (URN)10.1111/apm.12182 (DOI)000336447200011 ()24106819 (PubMedID)2-s2.0-84901231876 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research committee 

Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2018-06-04Bibliographically approved
Jonsson, T. B., Larzon, T., Arfvidsson, B., Tidefelt, U., Axelsson, C.-G., Jurstrand, M. & Norgren, L. (2012). Adverse events during treatment limb ischemia with autologous peripheral blood mononuclear cell implant. International Journal of Angiology, 31(1), 77-84
Open this publication in new window or tab >>Adverse events during treatment limb ischemia with autologous peripheral blood mononuclear cell implant
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2012 (English)In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 31, no 1, p. 77-84Article in journal (Refereed) Published
Abstract [en]

Aim: Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.

Methods: We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.

Results: Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.

Conclusion: Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.

Place, publisher, year, edition, pages
Turin, Italy: Edizioni Minerva Medica, 2012
National Category
Medical and Health Sciences Clinical Medicine
Research subject
Medicine; Surgery
Identifiers
urn:nbn:se:oru:diva-22554 (URN)000301822400011 ()22330628 (PubMedID)2-s2.0-84858858355 (Scopus ID)
Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2017-12-07Bibliographically approved
Ahlstrand, E., Persson, L., Tidefelt, U. & Söderquist, B. (2012). Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy. European Journal of Clinical Microbiology and Infectious Diseases, 31(7), 1679-1687
Open this publication in new window or tab >>Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
2012 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, p. 1679-1687Article in journal (Refereed) Published
Abstract [en]

The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.

Place, publisher, year, edition, pages
New York, USA: Springer, 2012
National Category
Clinical Medicine Infectious Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22579 (URN)10.1007/s10096-011-1493-6 (DOI)000304652800051 ()22124538 (PubMedID)2-s2.0-84865591558 (Scopus ID)
Note

Funding Agency:

research committee of Örebro County Council, Sweden

Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2018-04-16Bibliographically approved
Lehmann, S., Bykov, V., Ali, D., Andrén, O., Cherif, H., Tidefelt, U., . . . Andersson, P. (2012). Targeting p53 in vivo: a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. Journal of Clinical Oncology, 30(29), 3633-3639
Open this publication in new window or tab >>Targeting p53 in vivo: a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer
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2012 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 29, p. 3633-3639Article in journal (Refereed) Published
Abstract [en]

PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246.

PATIENTS AND METHODS: APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.

RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response.

CONCLUSION: We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.

Place, publisher, year, edition, pages
American Society of Clinical Oncology, 2012
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-27145 (URN)10.1200/JCO.2011.40.7783 (DOI)000309653600014 ()22965953 (PubMedID)2-s2.0-84867615093 (Scopus ID)
Note

Funding Agency:

Aprea, Stockholm, Sweden

Available from: 2013-01-30 Created: 2013-01-30 Last updated: 2017-12-06Bibliographically approved
Hultgren Hörnquist, E., Nilsson, K., Andersson, T., Tidefelt, U. & Lidskog, M. (2011). Building a PBL-based integrated curriculum for a new medical school in Sweden. In: : . Paper presented at Celebrating the Past and Embracing the Future: Evolution and Innovation in Problem-based Larning, Conference, Grange-Over-Sands, UK, March 30-31, 2011.
Open this publication in new window or tab >>Building a PBL-based integrated curriculum for a new medical school in Sweden
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2011 (English)Conference paper, Oral presentation only (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-24440 (URN)
Conference
Celebrating the Past and Embracing the Future: Evolution and Innovation in Problem-based Larning, Conference, Grange-Over-Sands, UK, March 30-31, 2011
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2018-02-05Bibliographically approved
Lehmann, S., Ravn, A., Carlsson, L., Antunovic, P., Deneberg, S., Möllgård, L., . . . Juliusson, G. (2011). Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia, 25(7), 1128-1134
Open this publication in new window or tab >>Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry
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2011 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 7, p. 1128-1134Article in journal (Refereed) Published
Abstract [en]

Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

Place, publisher, year, edition, pages
Nature Publishing Group, 2011
Keywords
acute promyelocytic leukemia; incidence; early mortality; hemorrhagic death; population based
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:oru:diva-22581 (URN)10.1038/leu.2011.78 (DOI)000292682600008 ()21502956 (PubMedID)2-s2.0-85027932070 (Scopus ID)
Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2018-02-19Bibliographically approved
Ahlstrand, E., Svensson, K., Persson, L., Tidefelt, U. & Söderquist, B. (2011). Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades. European Journal of Clinical Microbiology and Infectious Diseases, 30(11), 1349-1354
Open this publication in new window or tab >>Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
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2011 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 11, p. 1349-1354Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to determine if there was a long-term increase in glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated from patients with hematological malignancies. We conducted a retrospective single-center study where all positive blood cultures of S. epidermidis (n = 387) and S. haemolyticus (n = 19) isolated from patients with hematological malignancies during three decades, 1980 to 2009, were re-evaluated for the presence of reduced susceptibility to vancomycin and teicoplanin. Three different methods for the detection of reduced susceptibility to glycopeptides were used; standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD) Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin and teicoplanin did not show any statistically significant increase during the study period. The presence of heterogeneously glycopeptide-intermediate staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci (CoNS) isolates. hGIS were found in 31-45% of the CoNS isolates by the macromethod Etest and in 53-67% by the GRD Etest during the three decades. In conclusion, we did not observe any long-term glycopeptide MIC creep determined by the standard Etest, although a high and increasing proportion of heterogeneous vancomycin resistance was observed.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-20840 (URN)10.1007/s10096-011-1228-8 (DOI)000295864800006 ()
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2017-12-08Bibliographically approved
Lindgren, S., Brännström, T., Hanse, E., Ledin, T., Nilsson, G., Sandler, S., . . . Donner, J. (2011). Medical education in Sweden. Medical teacher, 33(10), 798-803
Open this publication in new window or tab >>Medical education in Sweden
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2011 (English)In: Medical teacher, ISSN 0142-159X, E-ISSN 1466-187X, Vol. 33, no 10, p. 798-803Article in journal (Refereed) Published
Abstract [en]

Undergraduate medical education in Sweden has moved from nationally regulated, subject-based courses to programmes integrated either around organ systems or physiological and patho-physiological processes, or organised around basic medical science in conjunction with clinical specialities, with individual profiles at the seven medical schools. The national regulations are restricted to overall academic and professional outcomes. The 51/2 year long university undergraduate curriculum is followed by a mandatory 18 months internship, delivered by the County Councils. While quality control and accreditation for the university curriculum is provided by the Swedish National Agency for Higher Education, no such formal control exists for the internship; undergraduate medical education is therefore in conflict with EU directives from 2005. The Government is expected to move towards 6 years long university undergraduate programmes, leading to licence, which will facilitate international mobility of both Swedish and foreign medical students and doctors. Ongoing academic development of undergraduate education is strengthened by the Bologna process. It includes outcome (competence)-based curricula, university Masters level complying with international standards, progression of competence throughout the curriculum, student directed learning, active participation and roles in practical clinical education and a national assessment model to assure professional competence. In the near future, the dimensioning of Swedish undergraduate education is likely to be decided more by international demands and aspects of quality than by national demands for doctors.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-20813 (URN)10.3109/0142159X.2011.570816 (DOI)000295218300010 ()
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2018-05-03Bibliographically approved
Deneberg, S., Guardiola, P., Lennartsson, A., Qu, Y., Gaidzik, V. E., Blanchet, O., . . . Lehmann, S. (2011). Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks. Blood, 118(20), 5573-5582
Open this publication in new window or tab >>Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks
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2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 20, p. 5573-5582Article in journal (Refereed) Published
Abstract [en]

Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.

Place, publisher, year, edition, pages
American Society of Hematology, 2011
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-22580 (URN)10.1182/blood-2011-01-332353 (DOI)000297265400028 ()21960591 (PubMedID)2-s2.0-81555214615 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Childhood Cancer FoundationSwedish Research Council
Note

Funding Agencies:

Göran Gustafssons Foundation for Research in Natural Sciences  

Sigurd och Elsa Golje Foundation  

Ligue Contre le Cancer  

La Region Pays de la Loire/Appel a Projets du Canceropole Grand-Ouest  

Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2018-05-03Bibliographically approved
Prenkert, M., Uggla, B., Tidefelt, U. & Strid, H. (2010). CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells. Anticancer Research, 30(10), 4157-61
Open this publication in new window or tab >>CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells
2010 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 10, p. 4157-61Article in journal (Refereed) Published
Abstract [en]

Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.

Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).

Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.

Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.

Place, publisher, year, edition, pages
Athens, Greece: International Institute of Anticancer Research, 2010
National Category
Medical and Health Sciences Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-37784 (URN)000283914400040 ()21036735 (PubMedID)2-s2.0-78650228378 (Scopus ID)
Available from: 2014-10-17 Created: 2014-10-15 Last updated: 2018-04-24Bibliographically approved
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