| 1. |
- Sjölund, Katarina, et al.
(författare)
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Downsizing treatment with tyrosine kinase inhibitors in patients with advanced gastrointestinal stromal tumors improved resectability.
- 2010
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 34:9, s. 2090-2097
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first-line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high-risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ-preserving surgery was facilitated. METHODS: Ten high-risk GIST-patients had downsizing/adjuvant TKI treatment: nine with imatinib and one with sunitinib. The patients were matched with historical controls (n = 89) treated with surgery alone, from our population-based series (n = 259). Mutational analysis of KIT and PDGFRA was performed in all cases. The progression-free survival was calculated. RESULTS: The primary tumors decreased in mean diameter from 20.4 cm to 10.5 cm on downsizing imatinib. Four patients with R0 resection and a period of adjuvant imatinib had no recurrences versus 67% in the historical control group. Four patients with residual liver metastases have stable disease on continuous imatinib treatment after surgery. One patient has undergone reoperation with liver resection. The downsizing treatment led to organ-preserving surgery in nine patients and improved preoperative nutritional status in one patient. CONCLUSIONS: Downsizing TKI is recommended for patients with bulky tumors with invasion of adjacent organs. Sunitinib can be used for patients in case of imatinib resistance (e.g., wild-type GISTs), underlining the importance of mutational analysis for optimal surgical planning.
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| 2. |
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| 3. |
- Arne, Gabriella, et al.
(författare)
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Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location, and poor prognosis.
- 2011
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 129:5, s. 1149-1161
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Tidskriftsartikel (refereegranskat)abstract
- In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on 9 tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, PDGFRA, or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, P=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, NIH risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.
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| 4. |
- Arne, Gabriella, et al.
(författare)
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Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
- 2013
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 52:4, s. 783-792
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Tidskriftsartikel (refereegranskat)abstract
- Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
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| 5. |
- Balkhed Östholm, Åse, 1972-, et al.
(författare)
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Duration of travel-associated faecal colonisation with ESBL-producing Enterobacteriaceae - A one year follow-up study
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, we found that 30% of individuals travelling outside Scandinavia acquired extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in their faecal flora. The aim of this study was to determine the duration of travel-associated faecal colonisation with ESBL-PE, to assess risk factors for prolonged colonisation and to detect changes in antibiotic susceptibility during prolonged colonisation.
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| 6. |
- Bümming, Per, 1965, et al.
(författare)
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Can the early reduction of tumour markers predict outcome in surgically treated sporadic medullary thyroid carcinoma?
- 2008
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Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2443. ; 393:5, s. 699-703
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Patients with sporadic medullary thyroid carcinoma (MTC) have a variable clinical course. Our aim was to analyse the reduction of tumour markers after thyroidectomy with meticulous dissection and relate it to clinical outcome. MATERIALS AND METHODS: Twenty consecutive patients with palpable sporadic MTC underwent thyroidectomy with central and uni- or bilateral modified radical neck dissection; three were subjected to mediastinal dissection. Basal (b-) and stimulated (s-) calcitonin (CT) and carcinoembryonic antigen (CEA)-levels were measured before and 6-8 weeks after primary surgery, and the reduction of these tumour markers was determined. RESULTS: Median CT (b- and s-) were markedly reduced after surgery (98.5% and 99.1%, respectively), and CEA decreased 11 times. CT (b-) fell >99% in seven patients after surgery; in these and four additional patients, CT (s-) showed a similar reduction. During follow-up (median 52.5 months), two patients (stages IV B and C) died of MTC; they had <95% reduction of CT. Four patients (stage IV A) are alive with verified metastases. Eight patients (one stage III, seven stage IV A) are alive with hypercalcitoninemia. Five stages I-III patients and one stage IV A patient are disease-free. CONCLUSIONS: Thyroidectomy and meticulous dissection caused a pronounced reduction of tumour markers. A postoperative reduction of CT (s-) >/=97% seems to be associated with less aggressive clinical course, while CEA had lower predictive value.
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| 7. |
- Bümming, Per, 1965, et al.
(författare)
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Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype.
- 2007
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Ingår i: Endocrine-related cancer. - 1351-0088. ; 14:3, s. 853-63
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal, which share many properties with neurons of the gastrointestinal tract. Recently, we demonstrated expression of the hormone ghrelin in GIST. The aim of the present study was therefore to evaluate a possible neuroendocrine phenotype of GIST. Specimens from 41 GISTs were examined for the expression of 12 different synaptic vesicle proteins. Expression of synaptic-like microvesicle proteins, e.g., Synaptic vesicle protein 2 (SV2), synaptobrevin, synapsin 1, and amphiphysin was demonstrated in a majority of GISTs by immunohistochemistry, western blotting, and quantitative reversetranscriptase PCR. One-third of the tumors also expressed the large dense core vesicle protein vesicular monoamine transporter 1. Presence of microvesicles and dense core vesicles in GIST was confirmed by electron microscopy. The expression of synaptic-like microvesicle proteins in GIST was not related to risk profile or to KIT/platelet derived growth factor alpha (PDGFRA) mutational status. Thus, GISTs regularly express a subset of synaptic-like microvesicle proteins necessary for the regulated secretion of neurotransmitters and hormones. Expression of synaptic-like micro-vesicle proteins, ghrelin and peptide hormone receptors in GIST indicate a neuroendocrine phenotype and suggest novel possibilities to treat therapy-resistant GIST.
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| 8. |
- Bümming, Per, 1965, et al.
(författare)
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Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1
- 2006
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:5, s. 626-30
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Tidskriftsartikel (refereegranskat)abstract
- There is rapid evolution in the functional imaging of tumours. In two patients with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST), previously unrecognized tumours were visualized by combined 2-tracer positron emission tomography (PET), which also provided precise information about tumour type. PET imaging led to radical resection and the diagnoses were histopathologically confirmed. GISTs from the Carney patient and the patient with neurofibromatosis type 1 (NF1) both lacked KIT mutations.
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| 9. |
- Claesson, Carina, 1970-, et al.
(författare)
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Susceptibility of staphylococci and enterococci to antimicrobial agents at different ward levels in four north European countries
- 2007
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:11-12, s. 1002-1012
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Tidskriftsartikel (refereegranskat)abstract
- A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively.
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| 10. |
- Ebenhag, Sven-Christian, 1976, et al.
(författare)
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Time transfer using an asynchronous computer network: Results from three weeks of measurements
- 2007
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Ingår i: European Frequency and Time Forum, 29/5 - 1/6, Geneva, CH.
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Konferensbidrag (refereegranskat)abstract
- We have performed a time transfer experimentbetween two atomic clocks, over a distance of approximately 75km using an 10 Gbit/s asynchronous fiber-optic computernetwork. The time transfer was accomplished through passivelistening on existing data traffic and a pilot sequence in the SDHbit stream. In order to assess the fiber-link clock comparison, wesimultaneously compared the clocks using a GPS carrier phaselink. The standard deviation of the difference between the twotime transfer links over the three-week time period was 243 ps.
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| 11. |
- Ekeblad, Sara, et al.
(författare)
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Gastrointestinal stromal tumors express the orexigen ghrelin
- 2006
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Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:3, s. 963-70
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
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| 12. |
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| 13. |
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| 14. |
- Holmbom, Martin, 1984-, et al.
(författare)
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Fluoroquinolone-resistant Escherichia coli among the rectal flora is the predominant risk factor for severe infection after transrectal ultrasound-guided prostate biopsy : a prospective observational study
- 2023
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden. - 2168-1805 .- 2168-1813. ; 58, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infection of the prostate gland following biopsy, usually with Escherichia coli, is a common complication, despite the use of antimicrobial prophylaxis. A fluoroquinolone (FQ) is commonly prescribed as prophylaxis. Worryingly, the rate of fluoroquinolone-resistant (FQ-R) E. coli species has been shown to be increasing. OBJECTIVE: This study aimed to identify risk factors associated with infection after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). METHODS: This was a prospective study on patients undergoing TRUS-Bx in southeast Sweden. Prebiopsy rectal and urine cultures were obtained, and antimicrobial susceptibility and risk-group stratification were determined. Multivariate analyses were performed to identify independent risk factors for post-biopsy urinary tract infection (UTI) and FQ-R E. coli in the rectal flora. RESULTS: In all, 283 patients were included, of whom 18 (6.4%) developed post-TRUS-Bx UTIs. Of these, 10 (3.5%) had an UTI without systemic inflammatory response syndrome (SIRS) and 8 (2.8%) had a UTI with SIRS. Being in the medium- or high-risk groups of infectious complications was not an independent risk factor for UTI with SIRS after TRUS-Bx, but low-level FQ-resistance (minimum inhibitory concentration (MIC): 0.125-0.25 mg/L) or FQ-resistance (MIC > 0.5 mg/L) among E. coli in the faecal flora was. Risk for SIRS increased in parallel with increasing degrees of FQ-resistance. Significant risk factor for harbouring FQ-R E.coli was travelling outside Europe within the previous 12 months. CONCLUSION: The predominant risk factor for UTI with SIRS after TRUS-Bx was FQ-R E. coli among the faecal flora. The difficulty in identifying this type of risk factor demonstrates a need for studies on the development of a general approach either with rectal swab culture for targeted prophylaxis, or prior rectal preparation with a bactericidal agent such as povidone-iodine before TRUS-Bx to reduce the risk of FQ-R E. coli-related infection.
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| 15. |
- Hällgren, Anita, 1963-, et al.
(författare)
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Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems
- 2001
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 48:1, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.
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| 16. |
- Hällgren, Anita, 1963-, et al.
(författare)
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Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units
- 2003
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 52:2, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- We studied 45 isolates of Enterococcus faecalis with high-level gentamicin resistance (HLGR), all but one concomitantly resistant to ciprofloxacin, and 25 ciprofloxacin-resistant isolates without HLGR for genetic relatedness using pulsed-field gel electrophoresis (PFGE). E. faecalis were isolated from patients admitted to intensive care units at eight hospitals in southern Sweden from December 1996 through December 1998. Genomic analysis by PFGE resulted in three clusters of genetically related isolates (designated clusters I, II and III) and 23 unique clones. Cluster I was found predominantly in the eastern and central parts of southern Sweden and clusters II and III in south-western Sweden. Among the 45 isolates with HLGR, 69% belonged to cluster I, 20% to cluster II, and 11% had unique PFGE patterns, which suggests that the majority of isolates with HLGR are closely related. Among the 25 ciprofloxacin-resistant isolates without HLGR, 68% had unique PFGE patterns, 12% belonged to cluster I and 20% to cluster III, which suggests the ciprofloxacin-resistant isolates are not related. All isolates with HLGR contained the aac(6′)Ie-aph(2″)Ia gene, which was carried on a Tn5281-like transposon in all isolates except one. We conclude that HLGR in E. faecalis was mainly due to dissemination of genetically related clones during the time studied, and that HLGR in these isolates was due to the presence of the aac(6′)Ie-aph(2″)Ia gene.
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| 17. |
- Kesarimangalam, Sriram, 1983, et al.
(författare)
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High diversity of bla NDM-1 -encoding plasmids in Klebsiella pneumoniae isolated from neonates in a Vietnamese hospital
- 2022
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 59:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam during the last 10 years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of blaNDM-1-encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study. Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the blaNDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients. Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding blaNDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding blaNDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same blaNDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques. Conclusions: The plasmids encoding the blaNDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis.
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| 18. |
- Lindskog, Stefan, et al.
(författare)
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Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618
- 2004
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 91:6, s. 713-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.
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| 19. |
- Nilsson, Bengt E, 1949, et al.
(författare)
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Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST)
- 2007
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:11, s. 1656-8
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Tidskriftsartikel (refereegranskat)abstract
- Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.
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| 20. |
- Nilsson, Bengt E, 1949, et al.
(författare)
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Treatment of gastrointestinal stromal tumours: imatinib, sunitinib -- and then?
- 2009
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Ingår i: Expert opinion on investigational drugs. - : Informa Healthcare. - 1744-7658 .- 1354-3784. ; 18:4, s. 457-68
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Tidskriftsartikel (refereegranskat)abstract
- With the discovery of gain-of-function mutations of KIT in a majority of gastrointestinal stromal tumours (GIST) and access to the tailored tyrosine kinase inhibitor (TKI) imatinib, a new era in cancer therapy started. The drug caused marked tumour responses in most patients with advanced GISTs, but could also be used in an adjuvant setting after radical surgery or as downstaging treatment before intentionally curative surgery. With prolonged treatment imatinib resistance can develop, most likely due to secondary KIT mutations. In this situation the second-line TKI sunitinib is well suited to patients with KIT exon 9 mutations, or for patients without KIT/PDGFRA mutations (wild-type GIST). New treatment is required to treat imatinib or sunitinib resistance. New-generation TKIs have broader target profiles and increased activity against certain targets; but also new principles have been proposed, for example dose escalation, inhibition of downstream signalling molecules, HSP90 chaperon inhibition, transcriptional repression, combination with chemotherapy or receptor-mediated therapy of highly expressed cell surface receptors. Targeting of cancer stem cells may be another option.
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| 21. |
- Nilsson, Helena, 1974-, et al.
(författare)
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A time trend study of significantly elevated perfluorocarboxylate levels in humans after using fluorinated ski wax
- 2010
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Ingår i: Environmental Science and Technology. - Washington, USA : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:6, s. 2150-2155
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Tidskriftsartikel (refereegranskat)abstract
- A time trend study focusing on ski waxing technicians' exposure to perfluorinated chemicals (PFCs) from fluorinated wax fumes was performed in 2007/2008. Levels of eight perfluorocarboxylates and three perfluorosulfonates were analyzed in monthly blood samples from eight technicians, Samples were collected before the ski season, i.e., preseason, then at four AS World Cup competitions in cross country skiing, and finally during an unexposed 5-month postseason period. The perfluorinated carboxylates perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) bioaccumulate, and continued exposure may contribute to elevated levels in ski technicians compared to the general population. The wax technicians' median blood level of PFOA is 112 ng/mL compared to 2.5 ng/mL in the general Swedish population. A significant correlation was found between number of working years and levels of perfluorocarboxylates. The PFOA levels in three technicians with "low" initial levels of PFOA (< 10.0 ng/mL in preseason blood) increased by 254, 134, and 120%, whereas five technicians with "high" initial levels (> 100 ng/mL in preseason sample) were at steady state. PFHxA is suggested to have a short half-life in humans relative the other perfluorocarboxylates. The levels of perfluorosulfonates were unaffected by the wax exposure.
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| 22. |
- Nilsson, Helena, 1974-, et al.
(författare)
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Biotransformation of fluorotelomer compound to perfluorocarboxylates in humans
- 2013
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 51, s. 8-12
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Tidskriftsartikel (refereegranskat)abstract
- Levels of perfluorocarboxylates (PFCAs) in biological compartments have been known for some time but their transport routes and distribution patterns are not properly elucidated. The opinions diverge whether the exposure of the general population occurs indirect through precursors or direct via PFCAs. Previous results showed that ski wax technicians are exposed to levels up to 92 000 ng/m(3) of 8:2 fluorotelomer alcohol (FTOH) via air and have elevated blood levels of PFCAs. Blood samples were collected in 2007-2011 and analyzed for C(4)-C(18) PFCAs, 6:2, 8:2 and 10:2 unsaturated fluorotelomer acids (FTUCAs) and 3:3, 5:3 and 7:3 fluorotelomer acids (FTCAs) using UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was detected in levels ranging from 1.90 to 628 ng/mL whole blood (wb). Metabolic intermediates 5:3 and 7:3 FTCA were detected in all samples at levels up to 6.1 and 3.9 ng/mL wb. 6:2, 8:2 and 10:2 FTUCAs showed maximum levels of 0.07, 0.64 and 0.11 ng/mL wb. Also, for the first time levels of PFHxDA and PFOcDA were detected in the human blood at mean concentrations up to 4.22 ng/mL wb and 4.25 ng/mL wb respectively. The aim of this study was to determine concentrations of PFCAs and FTOH metabolites in blood from ski wax technicians.
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| 23. |
- Nilsson, Helena, 1974-, et al.
(författare)
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Inhalation exposure to fluorotelomer alcohols yield perfluorocarboxylates in human blood?
- 2010
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:19, s. 7717-7722
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Tidskriftsartikel (refereegranskat)abstract
- Levels of perfluorinated carboxylates (PFCAs) in different environmental and biological compartments have been known for some time, but the routes of exposure still remain unclear. The opinions are divergent whether the exposure to general populations occurs mainly indirect through precursor compounds or direct via PFCAs. Previous results showed elevated blood levels of PFCAs in ski wax technicians compared to a general population. The objective of this follow-up study was to determine concentrations of PFCAs, perfluorosulfonates (PFSAs), and fluorotelomer alcohols (FTOHs), precursor compounds that are known to degrade to PFCAs, in air collected in the breathing zone of ski wax technicians during work. We collected air samples by using ISOLUTE ENV+ cartridges connected to portable air pumps with an air flow of 2.0 L min(-1). PFCAs C5-C11 and PFSAs C4, C6, C8, and C10 were analyzed using LC-MS/MS and FTOHs 6:2, 8:2, and 10:2 with GC-MS/MS. The results show daily inhalation exposure of 8:2 FTOH in mu g/m(3) air which is up to 800 times higher than levels of PFOA with individual levels ranging between 830-255000 ng/m(3) air. This suggests internal exposure of PFOA through biotransformation of 8:2 FTOH to PFOA and PFNA in humans.
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| 24. |
- Nilsson, Helena, 1974-, et al.
(författare)
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Professional ski waxers' exposure to PFAS and aerosol concentrations in gas phase and different particle size fractions
- 2013
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Ingår i: Environmental science. Processes & impacts. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 15:4, s. 814-822
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports show that professional ski waxers have elevated blood levels of perfluorinated substances (PFAS) such as perfluorooctanoate (PFOA) and are exposed to very high concentrations of PFAS in air during ski waxing. Aerosol exposure increases the risk of cardiovascular disease, and PFOA is a potential hormonal disruptor and carcinogen, and can affect the fatty acid metabolism. Animal studies have shown that 8: 2 FTOH can undergo biotransformation to PFOA. For the first time, this study presents an occupational scenario of professional ski waxers who are exposed to extremely high dust levels as well as per-and polyfluorinated compounds. Personal and fixed measurements of total aerosol, inhalable and respirable fractions were performed during World Cup events 2007-2010. The occupational exposure limit (OEL) is exceeded in 37% of the personal measurements with concentrations up to 15 mu g m(-3) in air. There are differences between personal and area total aerosol concentrations with levels from personal measurements twice as high as those from the area measurements. The personal levels for FTOH ranged up to 996 mg m(-3) (mean = 114 mu g m(-3)) and for PFOA up to 4.89 mu g m(-3) (mean = 0.53 mu g m(-3)) in ENV+ sorbent samples as compared to the general exposure levels from air reaching only low ng m(-3) (<30 ng m(-3)) levels. FTOHs were not detected in aerosols but PFOA showed an average level of 12 mu g m(-3) (range = 1.2-47 mu g m(-3)). The ski waxers' exposure to paraffin fumes and PFAS is not in compliance with the occupational exposure standards and by far exceed the general populations' exposure. Preventive measures must be taken to minimize the exposure in this occupational group.
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| 25. |
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| 26. |
- Wängberg, Bo, 1953, et al.
(författare)
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The long-term survival in adrenocortical carcinoma with active surgical management and use of monitored mitotane.
- 2010
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Ingår i: Endocrine-related cancer. - 1479-6821. ; 17:1, s. 265-72
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Tidskriftsartikel (refereegranskat)abstract
- Adrenocortical carcinoma (ACC) is a rare tumour disease with sinister prognosis also after attempts to radical surgery; better prognosis is seen for low-stage tumours. Adjuvant treatment with the adrenolytic drug mitotane has been attempted, but not proven to prevent from recurrence. The drug may offer survival advantage in case of recurrence. The aim of this single-centre study (1979-2007) of 43 consecutive patients was to evaluate the long-term survival after active surgical treatment combined with monitored mitotane (to reduce side effects of the drug). The series is unique, since all patients were offered a period of mitotane as adjuvant or palliative treatment; six patients refused mitotane. Despite a high proportion of high-stage tumours (67%), the complete resection rate was high (77%). The disease-specific 5-year survival was high (64.1%); very high for patients with low-stage tumours without evident relation to mitotane levels. Patients with high-stage tumours had a clear survival advantage with mitotane levels above a threshold of 14 mg/l in serum. The hazard ratio for patients with high mitotane levels versus all patients indicates a significant effect of the drug. The results indicate that adjuvant mitotane may be the standard of care for patients with high-stage ACC after complete resection.
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| 27. |
- Bümming, Per, 1965, et al.
(författare)
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Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:3, s. 460-4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
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| 28. |
- Bümming, Per, 1965, et al.
(författare)
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Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours
- 2006
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:7, s. 836-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.
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| 29. |
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| 30. |
- Hanberger, Håkan, 1954-, et al.
(författare)
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Intensive care unit
- 2005
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Ingår i: Antibiotic policies.. - New York : Springer. - 9780387228525 ; , s. 261-279
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- For 50 years, antibiotics have been dispensed like sweets. This must not be allowed to continue. This unique book assembles contributions from experts around the world concerned with responsible use of antibiotics and the consequences of overuse. For the first time, it provides up to the minute texts on both the theoretical aspects of antibiotic stewardship and the practical aspects of its implementation, with consideration of the key differences between developed and developing countries. All concerned with teaching, practice and administration of clinical medicine, surgery, pharmacy, public health, clinical pharmacology, microbiology, infectious diseases and clinical therapeutics will find Antibiotic Policies: Theory and Practice essential reading. Antibiotic use and resistance is not just the responsibility of specialists in the field but the responsibility of all doctors, pharmacists, nurses, healthcare administrators, patients and the general public.
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| 31. |
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| 32. |
- Hanberger, Håkan, 1954-, et al.
(författare)
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Low antibiotic resistance rates in Staphylococcus aureus, Escherichia coli and Klebsiella spp but not in Enterobacter spp and Pseudomonas aeruginosa : A prospective observational study in 14 Swedish ICUs over a 5-year period
- 2007
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 51:7, s. 937-941
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care units (ICUs) are hot zones for emergence and spread of antibiotic resistance because of frequent invasive procedures, antibiotic usage and transmission of bacteria. We report prospective data on antibiotic use and bacterial resistance from 14 academic and non-academic ICUs, participating in the ICU-STRAMA programme 1999-2003. Methods: The quantity of antibiotics delivered to each ICU was calculated as defined daily doses per 1000 occupied bed days (DDD1000). Specimens for culture were taken on clinical indications and only initial isolates were considered. Species-related breakpoints according to the Swedish Reference Group for Antibiotics were used. Antibiotic resistance was defined as the sum of intermediate and resistant strains. Results: Mean antibiotic use increased from 1245 DDD1000 in 1999 to 1510 DDD1000 in 2003 (P = 0.11 for trend). Of Staphylococcus aureus, 0-1.8% were methicillin resistant (MRSA). A presumptive extended spectrum beta-lactamase (ESBL) phenotype was found in <2.4% of Escherichia coli, based on cefotaxime susceptibility, except a peak in 2002 (4.6%). Cefotaxime resistance was found in 2.6-4.9% of Klebsiella spp. Rates of resistance among Enterobacter spp. to cefotaxime (20-33%) and among Pseudomonas aeruginosa to imipenem (22-33%) and ciprofloxacin (5-21%) showed no time trend. Conclusion: MRSA and cefotaxime-resistant E. coli and Klebsiella spp strains were few despite high total antibiotic consumption. This may be the result of a slow introduction of resistant strains into the ICUs, and good infection control. The cause of imipenem and ciprofloxacin resistance in P. aeruginosa could reflect the increased consumption of these agents plus spread of resistant clones. © 2007 The Authors.
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| 33. |
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| 34. |
- Holmbom, Martin, 1984-
(författare)
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Clinical Impact of Bloodstream Infections – Characterization, Risk factors and Outcome
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bloodstream infection (blood poisoning) and antibiotic resistance are increasing worldwide, and already cause the loss of millions of human lives each year. According to the World Health Organisation (WHO), bloodstream infections (BSIs) represent 20% of global mortality on a par with cardiac infarct, stroke, and major trauma. BSI may occur when bacteria from a focus of infection gain access to the circulation (bacteraemia). BSIs are usually divided into two subclasses: community- and hospital-onset infections, since disease this involves different patient groups, types of bacteria, and reasons for infection. Compared to other countries, Sweden has been fortunate in having a relatively low death rate from BSI and low antibiotic resistance. However, as our lifestyle changes, the age of the population increases with more disease as a result, and as the healthcare system responds, death from infection and antibiotic resistance are on the increase. It is important that we recognise ”warning symptoms” if we are to manage BSIs correctly and initiate effective treatment. It is difficult to design individualised empirical treatment, so it is very important to be aware of risk factors for BSI and local resistance patterns, and to have an effective management programme. Bacterial resistance to antibiotics is an increasing problem, especially in bowel organisms that can cause infections that are very difficult to treat. In short, antibiotic resistance arises as a result of evolutionary processes where bacteria protect themselves by developing resistance genes. These genes can be exchanged between similar organisms or transmitted to others that in turn cause resistant infection. The use of antibiotics leads to an evolutionary/selection process leading to resistance in bacteria, both normal and pathogenic, enabling resistant organisms to survive, thrive, and go on to cause infection. Antibiotic resistance is a threat to global health. This thesis aims to increase our awareness of a large group of patients who suffer bloodstream infection. BSIs are increasing globally, and the death toll is high. Antibiotic resistance is an increasing threat to the health of the population, and we are inundated by alarming reports of resistance getting out of control. What is the situation in Sweden, and can we identify risk factors for BSI and mortality? In Study I, our aim was to study the incidence and mortality of BSI in Östergötland. To be able to do this, a large patient population stretching over several years was required. The study design was thus population-based in the form of an observational cohort study where all blood culture results from 2000 to 2013 were analysed, and evaluated from clinical data. A total of 109,938 results were analysed resulting in 11,480 BSIs. We saw that the incidence of BSI increased by 64% (mostly community-onset BSIs). We also saw that mortality increased by 45%. These results illustrate the importance of nationwide cooperation to combat the increasing problem of BSI and its mortality, and the establishment of a nationwide BSI register. The aim of Study II was to assess resistance development in Östergötland and its relationship to mortality. A total of 9,587 microorganisms were analysed between 2008 and 2016. We observed an increase in quinolone resistance (3.7-7.7%) and cephalosporin resistance (2.5-5.2%) amongst Enterobacteriaceae. We then looked at BSIs caused by multiresistant bacteria showing a total of 245 cases (2.6%); an increase of 300%. Despite this, we did not see an increased mortality in this group. There are several possible explanations for the increase in BSI mortality of which antibiotic resistance is a predominant factor globally. We were unable to show this in our study, even so mortality is increasing and is currently at a high level. In Study III we therefore analysed risk factors associated with death during a community-acquired BSI, focusing on preliminary prehospital and hospital management. In a retrospective case-control study on 195 deaths matched 1:1 regarding age, gender, and microorganism, with 195 survivors (controls). Results showed that many patients had contacted the primary healthcare system because of infection before they became severely ill, and that the strongest affectable risk factor for death was delay (>24h) between primary healthcare visit and admission to hospital. This shows the need for increased awareness in society and amongst the medical profession of those patients at risk and symptoms that should raise the alarm, leading to more rapid treatment. In Studies I and II we found an increase in both BSIs and mortality, we also saw an increase in antibiotic resistance and multiresistant bacteria, mainly ESBL-producing E. coli. On the other hand, we did not see any coupling between multiresistance and mortality in this Swedish population. E. coli is a gram-negative bacteria that causes most BSIs. Since E. coli is predominantly a urine tract pathogen, Study IV aimed to study BSIs caused by ESBL-producing E. coli originating from the urinary tract. We studied the prevalence of E. coli clones, resistance genes and risk factors, as well as any signs of increased mortality from ESBL-producing E. coli compared to sensitive E. coli. Our main finding was a surprisingly low mortality from ESBL-producing E. coli (3%). Most patients in the ESBL-producing E. coli group received inadequate antibiotic treatment for at least 48h, but we did not see any sign of increased mortality or risk for serious sepsis with circulatory failure in this group. This finding is interesting and opens up for new studies on virulence factors and immunological factors that govern the immune response to BSI. The implementation of cost-effective monitoring systems including clinical microbiological epidemiology and early identification of BSI, together with information campaigns aimed at the public as well as healthcare personnel regarding patients at risk and symptoms giving cause for alarm, should lead to a radical reduction in morbidity and mortality from BSI. This requires new diagnostic tools to individualise both antibiotic treatment and targeted management based on microorganism virulence factors. Modernisation of the medical journal system with algorithms aimed at early identification of risk patients and automated suggestions for empirical antibiotic treatment based on antibiotic resistance seen in previous cultures and local resistance patterns, would certainly improve management. Furthermore, new immunological tests showing the type of immunological reaction to a serious BSI will lead to individualised immunotherapy that, together with antibiotic treatment, will further improve patient care in this important group.
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| 35. |
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| 36. |
- Hällgren, Anita, et al.
(författare)
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Molecular detection of aggregation substance, enterococcal surface protein, and cytolysin genes and in vitro adhesion to urinary catheters of Enterococcus faecalis and E. faecium of clinical origin
- 2009
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 299:5, s. 323-332
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that nosocomial enterococci might have virulence factors that enhance their ability to colonise hospitalised patients. The objectives of this study were to investigate the prevalence of genes encoding 3 virulence factors: aggregation substance (asa1), enterococcal surface protein (esp), and 5 genes within the cytolysin operon (cylA, cylB, cylM, cylL(L), cylL(S)) and cytolysin production in 115 enterococcal clinical isolates (21 Enterococcus faecium and 94 E. faecalis). Adhesion to siliconized latex urinary catheters in relation to presence of esp was analysed in a subset of isolates. The isolates were previously characterised by pulsed-field gel electrophoresis (PFGE). esp was the only virulence gene found in E. faecium. It was found in 71% of the 21 E. faecium isolates. asa1, esp, and the cyl operon were found in 79%, 73% and 13% respectively, of the 94 E. faecalis isolates. There was a complete agreement between presence of the cyl operon and phenotypic cytolysin production. Isolates belonging to a cluster of genetically related isolates carried esp and asa1 more often when compared to unique isolates. No difference was found with respect to cyl genes. E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared. In conclusion, E. faecalis isolates with high-level gentamicin resistance (HLGR) belonging to clusters of genetically related isolates widely distributed in Swedish hospitals, were likely to carry both esp and asa1. Adhesion was not affected by esp.
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| 37. |
- Hällgren, Anita, 1963-, et al.
(författare)
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Rectal colonization and frequency of enterococcal cross-transmission among prolonged-stay patients in two Swedish intensive care units
- 2005
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 37:8, s. 561-571
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to gain insight into the dynamics of the rectal flora during prolonged ICU stay, with a particular focus on colonization and cross-transmission with resistant pathogens, and to evaluate methods for the rapid isolation of relevant bacteria from rectal swabs. Patients admitted to a general intensive care unit (GICU) or a cardiothoracic ICU (TICU) at the University Hospital of Linköping, Sweden, between 1 November 2001 and January 2002 with a length of stay > 5 d were included (n = 20). Chromogenic UTI agar medium was used for discrimination of different species, and appropriate antibiotics were added to detect resistance. Direct plating was compared to enrichment broth for a subset of specimens. The study showed an early alteration in rectal flora, with a dramatic decrease in Gram-negative rods in favour of Gram-positive bacteria. An ampicillin- and high-level gentamicin resistant clone of Enterococcus faecium was found in 6 of 10 patients in the GICU and 2 of 11 patients in the TICU. Enrichment broth did not enhance the detection of Gram-negative bacteria compared to direct plating on Chromogenic UTI medium, but enrichment broths were needed for optimal detection of resistant Gram-positive bacteria.
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| 38. |
- Malmberg, Per, 1974, et al.
(författare)
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High-resolution, imaging TOF-SIMS: novel applications in medical research
- 2011
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Ingår i: ANALYTICAL AND BIOANALYTICAL CHEMISTRY. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 399:8, s. 2711-2718
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The use of high-resolution, imaging TOF-SIMS is described and examples are made to demonstrate the application of the method in medical research. Cytochemistry by TOF-SIMS is shown by localization of diacylglycerol (DG) in cryostat sections of hyaline cartilage and by localization of corticosterone in cryostat sections of the adrenal gland cortex. Quantitative measurements and comparison of groups is shown by comparing the lipid content of adipose tissue from two mouse strains, transgenic mouse expressing the FOXC2 gene and wild-type controls. Finally, biopsies made for histopathological diagnosis of infantile reversible cytochrome c oxidase deficiency myopathy were analyzed in order to define the chemical content of areas showing a pathological structure in the light microscope. The use of high-resolution, imaging TOF-SIMS in medical research allows analysis of intact tissue and probe-free localization of specific target molecules in cells and tissues. The TOF-SIMS analysis is not dependent on penetration of reagents into the sample and also independent of probe reactivity such as cross-reactivity or background staining. The TOF-SIMS method can be made quantitative and allows for analysis of specific target molecules in defined tissue compartments.
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| 39. |
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| 40. |
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| 41. |
- Nilsson, Margareta, 1957-, et al.
(författare)
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Female urinary incontinence : patient-reported outcomes 1 year after midurethral sling operations
- 2012
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Ingår i: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 0937-3462 .- 1433-3023. ; 23:10, s. 1353-1359
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION AND HYPOTHESIS: Although midurethral slings have become standard surgical methods to treat stress urinary incontinence (SUI), little is known about women who still have urinary incontinence (UI) after surgery. This study assesses and compares the patient-reported outcome 12 months after tension-free vaginal tape (TVT), tension-free vaginal tape-obturator (TVT-O), and transobturator tape (TOT), with a special focus on women who still have urinary leakage postoperatively.METHODS: This study analyzed preoperative and 12-month postoperative data from 3,334 women registered in the Swedish National Quality Register for Gynecological Surgery.RESULTS: Among the women operated with TVT (n = 2,059), TVT-O (n = 797), and TOT (n = 478), 67 %, 62 %, and 61 %, respectively, were very satisfied with the result at the 1-year follow-up. There was a significantly higher chance of becoming continent after TVT compared with TOT. In total, 977 women (29 %) still had some form of urinary leakage postoperatively. Among the postoperatively incontinent women who expressed a negative impact of UI on family, social, work, and sexual life preoperatively, considerably fewer reported a negative impact in all domains after surgery. Of those in the postoperatively incontinent group who had coital incontinence preoperatively, 63 % reported a cure of coital incontinence.CONCLUSIONS: The proportion of women very satisfied with the result of the operation did not differ between the three groups. TVT had a higher SUI cure rate than did TOT. Despite urinary leakage 1-year postoperatively, half of the women were satisfied with the result of the operation.
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| 42. |
- Nord, Anette, et al.
(författare)
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Effect of two additional interventions, test and reflection, added to standard cardiopulmonary resuscitation training on seventh grade students' practical skills and willingness to act : a cluster randomised trial.
- 2017
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this research is to investigate if two additional interventions, test and reflection, after standard cardiopulmonary resuscitation (CPR) training facilitate learning by comparing 13-year-old students' practical skills and willingness to act.SETTINGS: Seventh grade students in council schools of two municipalities in south-east Sweden.DESIGN: School classes were randomised to CPR training only (O), CPR training with a practical test including feedback (T) or CPR training with reflection and a practical test including feedback (RT). Measures of practical skills and willingness to act in a potential life-threatening situation were studied directly after training and at 6 months using a digital reporting system and a survey. A modified Cardiff test was used to register the practical skills, where scores in each of 12 items resulted in a total score of 12-48 points. The study was conducted in accordance with current European Resuscitation Council guidelines during December 2013 to October 2014.PARTICIPANTS: 29 classes for a total of 587 seventh grade students were included in the study.PRIMARY AND SECONDARY OUTCOME MEASURES: The total score of the modified Cardiff test at 6 months was the primary outcome. Secondary outcomes were the total score directly after training, the 12 individual items of the modified Cardiff test and willingness to act.RESULTS: At 6 months, the T and O groups scored 32 (3.9) and 30 (4.0) points, respectively (p<0.001), while the RT group scored 32 (4.2) points (not significant when compared with T). There were no significant differences in willingness to act between the groups after 6 months.CONCLUSIONS: A practical test including feedback directly after training improved the students' acquisition of practical CPR skills. Reflection did not increase further CPR skills. At 6-month follow-up, no intervention effect was found regarding willingness to make a life-saving effort.
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| 43. |
- Nord, Anette, et al.
(författare)
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The effect of a national web course "Help-Brain-Heart" as a supplemental learning tool before CPR training: : a cluster randomised trial.
- 2017
-
Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effectiveness of cardiopulmonary resuscitation (CPR) learning methods is unclear. Our aim was to evaluate whether a web course before CPR training, teaching the importance of recognition of symptoms of stroke and acute myocardial infarction (AMI) and a healthy lifestyle, could influence not only theoretical knowledge but also practical CPR skills or willingness to act in a cardiac arrest situation.METHODS: Classes with 13-year-old students were randomised to CPR training only (control) or a web course plus CPR training (intervention). Data were collected (practical test and a questionnaire) directly after training and at 6 months. CPR skills were evaluated using a modified Cardiff test (12-48 points). Knowledge on stroke symptoms (0-7 points), AMI symptoms (0-9 points) and lifestyle factors (0-6 points), and willingness to act were assessed by the questionnaire. The primary endpoint was CPR skills at 6 months. CPR skills directly after training, willingness to act and theoretical knowledge were secondary endpoints. Training and measurements were performed from December 2013 to October 2014.RESULTS: Four hundred and thirty-two students were included in the analysis of practical skills and self-reported confidence. The mean score for CPR skills was 34 points after training (control, standard deviation [SD] 4.4; intervention, SD 4.0; not significant [NS]); and 32 points at 6 months for controls (SD 3.9) and 33 points for intervention (SD 4.2; NS). At 6 months, 73% (control) versus 80% (intervention; P = 0.05) stated they would do compressions and ventilation if a friend had a cardiac arrest, whereas 31% versus 34% (NS) would perform both if the victim was a stranger. One thousand, two hundred and thirty-two students were included in the analysis of theoretical knowledge; the mean scores at 6 months for the control and intervention groups were 2.8 (SD 1.6) and 3.2 (SD 1.4) points (P < 0.001) for stroke symptoms, 2.6 (SD 2.0) and 2.9 (SD 1.9) points (P = 0.008) for AMI symptoms and 3.2 (SD 1.2) and 3.4 (SD 1.0) points (P < 0.001) for lifestyle factors, respectively.DISCUSSION: Use of online learning platforms is a fast growing technology that increases the flexibility of learning in terms of location, time and is available before and after practical training.CONCLUSIONS: A web course before CPR training did not influence practical CPR skills or willingness to act, but improved the students' theoretical knowledge of AMI, stroke and lifestyle factors.
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| 44. |
- Pham, Thi Anh Mai, et al.
(författare)
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Evaluation of screening algorithms to detect rectal colonization with carbapenemase-producing Enterobacterales in a resource-limited setting
- 2024
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Ingår i: JAC - Antimicrobial Resistance. - : OXFORD UNIV PRESS. - 2632-1823. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources.Methods A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR).Results Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases.Conclusions These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.
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| 45. |
- Saeedi, Baharak, 1972-, et al.
(författare)
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Genetic relatedness of Enterococcus faecalis isolates with high-level gentamicin resistance from patients with bacteraemia in the south east of Sweden 1994-2001
- 2004
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:6-7, s. 405-409
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Tidskriftsartikel (refereegranskat)abstract
- High-level gentamicin resistant (HLGR) enterococci (Enterococcus faecalis and Enterococcus faecium) have become a substantial nosocomial problem in many countries. In this study, we investigated the prevalence of HLGR enterococci and their genetic relatedness in blood culture isolates from patients with bacteraemia admitted to the 3 hospitals in Östergötland, a county in the south east of Sweden, during 1994–2001. 36 of 250 E. faecalis (14%) and 4 of 106 E. faecium isolates (4%) were shown by PCR to carry the aac(6′)-Ie-aph(2″)-Ia aminoglycoside modifying gene and these isolates were also classified as HLGR enterococci by the gentamicin antibiotic disk diffusion method. A majority of HLGR E. faecalis isolates (83%) belonged to the same cluster of genetically related isolates, according to the pulsed-field gel electrophoresis (PFGE) patterns, whereas all 4 HLGR E. faecium isolates had unique PFGE patterns. In conclusion, our study showed that in contrast to studies from many other countries, the presence of HLGR enterococci was more common in E. faecalis than in E. faecium and appeared the first time in 1996 and 1999, respectively. Bacteraemia with HLGR enterococci in Östergötland was mainly due to the spread of a cluster related of E. faecalis strains.
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| 46. |
- Saeedi, Baharak, 1972-, et al.
(författare)
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Modified pulsed-field gel electrophoresis protocol for typing of enterococci
- 2002
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 110:12, s. 869-874
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Tidskriftsartikel (refereegranskat)abstract
- Controlling the spread of vancomycin-resistant enterococci (VRE) is an important task in hospital epidemiology. Pulsed-field gel electrophoresis (PFGE) has become the golden standard for molecular epidemiological characterisation of enterococcal isolates. For separation of DNA fragments by PFGE, different electrophoresis conditions have been recommended, but none of these protocols allows a satisfactory separation of both small and large DNA fragments of enterococci simultaneously. In this study we have speeded up the preparation of chromosomal DNA and defined new electrophoresis conditions that enhance separation of small and large DNA fragments for subtyping of enterococci with a 24 h PFGE.
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| 47. |
- Saeedi, Baharak, 1972-, et al.
(författare)
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Phene Plate (PhP) biochemical fingerprinting : a screening method for epidemiological typing of enterococcal isolates?
- 2005
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 113:9, s. 603-612
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Tidskriftsartikel (refereegranskat)abstract
- Pulsed-field gel electrophoresis (PFGE) is currently considered the gold standard for genotyping of enterococci. However, PFGE is both expensive and time-consuming. The purpose of this study was to investigate whether the PhP system can be used as a reliable clinical screening method for detection of genetically related isolates of enterococci. If so, it should be possible to minimize the number of isolates subjected to PFGE typing, which would save time and money. Ninety-nine clinical enterococcal isolates were analysed by PhP (similarity levels 0.90–0.975) and PFGE (similarity levels ≤3 and ≤6 bands) and all possible pairs of isolates were cross-classified as matched or mismatched. We found that the probability that a pair of isolates (A and B) belonging to the same type according to PhP also belong to the same cluster according to PFGE, i.e. p(APFGE=BPFGE • APhP=BPhP), and the probability that a pair of isolates of different types according to PhP also belong to different clusters according to PFGE, i.e. p(APFGE≠BPFGE • APhP≠BPhP), was relatively high for E. faecalis (0.86 and 0.96, respectively), but was lower for E. faecium (0.51 and 0.77, respectively). The concordance which shows the probability that PhP and PFGE agree on match or mismatch was 86%–93% for E. faecalis and 54%–66% for E. faecium, which indicates that the PhP method may be useful for epidemiological typing of E. faecalis in the current settings but not for E. faecium.
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| 48. |
- Schaufelberger, Maria, 1954, et al.
(författare)
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Can brain natriuretic peptide (BNP) be used as a screening tool in general practice?
- 2004
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Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 22:3, s. 187-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To investigate plasma brain natriuretic peptide (p-BNP) in consecutive primary care patients for heart failure screening. DESIGN: Open, descriptive. SETTING: Three primary care clinics, university hospital. SUBJECTS: 291 consecutive patients, > or =40 years. MAIN OUTCOME MEASURES: p-BNP and general practitioners estimated probability of CHF. RESULTS: Median p-BNP was 29 ng/L. In 42% p-BNP was >40 ng/L in the first sample. In 41 patients further investigated, median p-BNP was 98 ng/L, with a correlation between p-BNP and physicians' estimation of probability of heart failure (r=0.469, p<0.0001). New York Heart Association class was correlated to p-BNP (r=0.343, p=0.034). No correlation between ejection fraction and p-BNP was seen. CONCLUSION:P-BNP concentrations in unselected primary care patients of 40 years of age or above were elevated in a larger proportion of patients than previously reported. Owing to the low specificity, p-BNP concentration limits have to be defined before the test can be used for screening in primary care.
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| 49. |
- Simonsson, Tomas, 1965, et al.
(författare)
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Reducing uncertainty in health-care resource allocation
- 2007
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:12, s. 1834-8
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Tidskriftsartikel (refereegranskat)abstract
- A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful.
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| 50. |
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