| 721. |
- Pedersen, LN, et al.
(författare)
-
Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine
- 2003
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 38:8, s. 845-849
-
Tidskriftsartikel (refereegranskat)abstract
- Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (>20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.
|
|
| 722. |
- Persson, Asa, et al.
(författare)
-
Long-term exposure to transportation noise and obesity: A pooled analysis of eleven Nordic cohorts
- 2024
-
Ingår i: ENVIRONMENTAL EPIDEMIOLOGY. - 2474-7882. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Available evidence suggests a link between exposure to transportation noise and an increased risk of obesity. We aimed to assess exposure-response functions for long-term residential exposure to road traffic, railway and aircraft noise, and markers of obesity. Methods:Our cross-sectional study is based on pooled data from 11 Nordic cohorts, including up to 162,639 individuals with either measured (69.2%) or self-reported obesity data. Residential exposure to transportation noise was estimated as a time-weighted average L-den 5 years before recruitment. Adjusted linear and logistic regression models were fitted to assess beta coefficients and odds ratios (OR) with 95% confidence intervals (CI) for body mass index, overweight, and obesity, as well as for waist circumference and central obesity. Furthermore, natural splines were fitted to assess the shape of the exposure-response functions. Results:For road traffic noise, the OR for obesity was 1.06 (95% CI = 1.03, 1.08) and for central obesity 1.03 (95% CI = 1.01, 1.05) per 10 dB L-den. Thresholds were observed at around 50-55 and 55-60 dB L-den, respectively, above which there was an approximate 10% risk increase per 10 dB L-den increment for both outcomes. However, linear associations only occurred in participants with measured obesity markers and were strongly influenced by the largest cohort. Similar risk estimates as for road traffic noise were found for railway noise, with no clear thresholds. For aircraft noise, results were uncertain due to the low number of exposed participants. Conclusion:Our results support an association between road traffic and railway noise and obesity.
|
|
| 723. |
|
|
| 724. |
- Pihl, Elsa, et al.
(författare)
-
The proximal hamstring avulsion clinical trial (PHACT)-a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions : study protocol
- 2019
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:9
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The treatment of proximal hamstring avulsions is controversial. While several trials have investigated the outcome for patients treated surgically, there is today no prospective trial comparing operative treatment with non-operative treatment. This protocol describes the design for the proximal hamstring avulsion clinical trial (PHACT)-the first randomised controlled trial of operative versus non-operative treatment for proximal hamstring avulsions. Methods and analysis PHACT is a multicentre randomised controlled trial conducted across Sweden, Norway and Finland. Eligible patients (60 participants/treatment arm) with a proximal hamstring avulsion of at least two of three tendons will be randomised to either operative or non-operative treatment. Participants allocated to surgery will undergo reinsertion of the tendons with suture anchors. The rehabilitation programme will be the same for both treatment groups. When patient or surgeon equipoise for treatment alternatives cannot be reached and randomisation therefore is not possible, patients will be invited to participate in a parallel observational non-randomised cohort. The primary outcome will be the patient-reported outcome measure Perth hamstring assessment tool at 24 months. Secondary outcomes include the Lower Extremity Functional Score, physical performance and muscle strength tests, patient satisfaction and MR imaging. Data analysis will be blinded and intention-to-treat analysis will be preformed. Ethics and dissemination Ethical approval has been granted by the Ethical Committee of Uppsala University (DNR: 2017-170) and by the Norwegian ethical board (REC: 2017/1911). The study will be conducted in agreement with the Helsinki declaration. The findings will be disseminated in peer-reviewed publications.
|
|
| 725. |
|
|
| 726. |
- Pivnenko, Kostyantyn, et al.
(författare)
-
Quantification of chemical contaminants in the paper and board fractions of municipal solid waste
- 2016
-
Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 51, s. 43-54
-
Tidskriftsartikel (refereegranskat)abstract
- Chemicals are used in materials as additives in order to improve the performance of the material or the production process itself. The presence of these chemicals in recyclable waste materials may potentially affect the recyclability of the materials. The addition of chemicals may vary depending on the production technology or the potential end-use of the material. Paper has been previously shown to potentially contain a large variety of chemicals. Quantitative data on the presence of chemicals in paper are necessary for appropriate waste paper management, including the recycling and re-processing of paper. However, a lack of quantitative data on the presence of chemicals in paper is evident in the literature. The aim of the present work is to quantify the presence of selected chemicals in waste paper derived from households. Samples of paper and board were collected from Danish households, including both residual and source-segregated materials, which were disposed of (e.g., through incineration) and recycled, respectively. The concentration of selected chemicals was quantified for all of the samples. The quantified chemicals included mineral oil hydrocarbons, phthalates, phenols, polychlorinated biphenyls, and selected toxic metals (Cd, Co, Cr, Cu, Ni, and Pb). The results suggest large variations in the concentration of chemicals depending on the waste paper fraction analysed. Research on the fate of chemicals in waste recycling and potential problem mitigation measures should be focused on in further studies.
|
|
| 727. |
- Pulczynski, Elisa Jacobsen, et al.
(författare)
-
Age-adjusted combined immunochemotherapy without radiotherapy in newly diagnosed PCNSL : A phase II trial of the Nordic Lymphoma Group
- 2011
-
Ingår i: 53rd ASH Anual Meeting and Exposition. ; , s. 696-696
-
Konferensbidrag (refereegranskat)abstract
- Patients and Methods: From May 2007 to October 2010, 66 newly diagnosed primary central nervous system lymphoma (PCNSL) patients (M/F ratio 1:1) were enrolled. Younger patients (≤65 yrs; N=39) received 6 three-weekly cycles of chemotherapy consisting of: high-dose (HD)-methotrexate (MTX) (cycles 1, 2, 4 and 5), HD-cytosine arabinoside (AraC) (cycles 3 and 6) in addition to Rituximab (cycle 1 only), ifosfamide (cycles 1 and 4), cyclophosphamide (cycles 2 and 5), vincristine (cycles 2 and 5), vindesine (cycles 3 and 6), and dexamethasone (all 6 cycles). Depocyte® was delivered intratechally during the HD-MTX cycles. Elderly patients (66-75 yrs; N=27) received an identical Rituximab-containing 1st cycle. Cyclophosphamide and ifosfamide were replaced by temozolamide (cycles 2 to 6), which was also given as maintenance in patients with chemosensitive disease, and vincristine was omitted. No radiotherapy was given. Response was determined after the 2nd, 4th and 6thchemotherapy cycle by cerebral MRI and assessed according to International Primary CNS Lymphoma Coordinating Group criteria. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), overall response rate (ORR), systemic toxicity and neurotoxicity assessed as Mini Mental State Examination (MMSE) and Functional Independence Measure (FIM). Results: The median age was 64 yrs overall, 55 yrs (range 40-65) for younger and 70 yrs (range 66-75 years) for elderly patients. In 56 patients, the International Extranodal Lymphoma Study Group prognostic score was: 0-1 (N=5), 2-3 (N=36) and 4-5 (N=15). In the remaining 10 patients, lumbar puncture was not performed in five and spinal fluid protein concentration not reported in additional five cases. Response assessment after completion of induction treatment was performed in 43 out of 66 patients and showed complete remission (CR/CRu) in 30 patients, partial remission (PR) in 5 and progressive disease (PD) in 8. The ORR was 53 %. In 23 patients, response could not be evaluated due to early progression (n=8), toxic death (n=4), poor performance (n=3), neurotoxicity (n=5), or other causes (n=3). Of the 27 elderly patients, 15 continued to maintenance therapy. Of these, 14 have completed the maintenance schedule. Remission status at month 3 was CR in 13 and PD in 1 patient. With a median follow-up of 11.1 months (range 0.6-40.2) the 3-yr OS was 54.6% with no significant difference between younger and elderly patients (56.4% vs 51.9% respectively, p=0.32). The 3-yr PFS was 35.1% (32.9% in younger and 38.2 % in elderly patients; p=0.96). There were four septic deaths. Grade 3-4 hematological toxicity was seen in 79 % of the patients. Arachnoditis-like symptoms occurred in 13 patients. In all but two patients, the symptoms resolved within less than a week. MMSE and FIM were recorded both before and after therapy in 32 patients. Scores improved in 18 and 20 patients, respectively. Conclusion: In conclusion, the schedule applied in the present study led to a 3 yr PFS of 35%. Surprisingly, no significant outcome difference was found between the younger and the elderly patients. The majority of treatment failures were due to early progressive disease under induction therapy. Although the follow-up of our study is short, de-escalation of induction treatment intensity by introduction of a less toxic agent as temozolomide, and its subsequent use in a maintenance schedule may explain a possible survival benefit of this strategy in elderly patients. Disclosures: No relevant conflicts of interest to declare.
|
|
| 728. |
|
|
| 729. |
- Pulczynski, Elisa J, et al.
(författare)
-
Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase 2 study by The Nordic Lymphoma Group.
- 2015
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:4, s. 534-540
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Nordic Lymphoma Group has conducted a phase ll trial in primary central nervous system lymphoma patients applying age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Design and Methods: Patients with newly diagnosed PCNSL aged 18-75 years were eligible. Sixty-six patients (median age 64 years) were enrolled. Two age groups were predefined as those of 18-65 and 66-75 years of age. Results: The overall response rate was 90.8 %. With a median follow-up of 22 months, the 2-year overall survival probability was 60.7 % in patients < 65 years and 55.6% in patients > 65 years (p= 0.40). The estimated progression-free survival at 2 years was 33.1% (CI: 19.1%-47.9%) in patients < 65 years and 44.4% (CI: 25.6%-61.8%) in the elderly subgroup (p=0.74). Median duration of response was 10 months in the younger, not reached in the elderly patients (p=0.33). Four patients aged 64-75 years (6 %) died from treatment related complications. Conclusion: Survival in the two age groups was similar despite a de-escalation of induction treatment in patients > 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern especially in the elderly patients we conclude from these data that de-escalation of induction therapy in elderly PCNSL patients followed by maintenance treatment seems to be a promising treatment strategy. Trial registration: ClinicalTrials.gov number NCT01458730.
|
|
| 730. |
- Pulkka, Olli Pekka, et al.
(författare)
-
Fibrinogen-like protein 2 in gastrointestinal stromal tumour
- 2022
-
Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 26:4, s. 1083-1094
-
Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2. FGL2 expression was associated with small GIST size, low mitotic counts and low tumour-infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence-free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2-negative GIST appeared to benefit most from long duration of adjuvant imatinib. We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.
|
|
