| 1. |
- Andersen, Niels S., et al.
(författare)
-
Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
- 2009
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
|
|
| 2. |
- Blomstrand, Ann, et al.
(författare)
-
Low-budget method for lifestyle improvement in primary care. Experiences from the Göteborg Health Profile Project.
- 2005
-
Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 23:2, s. 82-7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe a self-administered preventive tool dealing with risk factors for cardiovascular disease and its effect with special reference to the question: did the project involve persons most in need of lifestyle changes? DESIGN: Screening questions offered to consecutive patients and followed by a self-administered health profile, intervention, and follow-up. Setting. Primary healthcare area of Askim, Sweden. SUBJECTS: Men and women between 18 and 65 years of age visiting GPs for acute disorders or planned visits during a three-month period were offered screening questions and, if wanted, a health profile. MAIN OUTCOME MEASURES: Participation rates, effects on lifestyle factors. RESULTS: There was an overrepresentation of subjects with a less favourable lifestyle among those who asked for the health profile. There was good agreement for all variables between self-estimation in screening questions and grading in the basal health profile. Lifestyle improvement was observed for dietary habits, physical activity, and mental stress at the one year follow-up. CONCLUSIONS: The results indicate that a relevant selection of persons with a "risk profile" can be made by means of simple screening questions. The pedagogic model using self-administered health profile in combination with own responsibility seems to be a tool for low-budget preventive work in primary healthcare.
|
|
| 3. |
- Geisler, Christian H., et al.
(författare)
-
Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue : a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2687-93
-
Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Lage, Kasper, et al.
(författare)
-
A human phenome-interactome network of protein complexes implicated in genetic disorders
- 2007
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 25:3, s. 309-316
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease-promoting genes that will inform future experimentation.
|
|
| 7. |
- Thomsen, J, et al.
(författare)
-
Optical Doppler tomography for monitoring vascularization during photodynamic therapy of skin cancer lesions
- 2008
-
Ingår i: BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE. - : SPIE. - 1996-756X .- 0277-786X. - 9780819471895 ; 6991
-
Konferensbidrag (refereegranskat)abstract
- We investigate vascular changes during Photodynamic therapy (PDT) of skin tumors using optical Doppler tomography (ODT). The effect of vascular shut down on tumor destruction is currently not known, and to optimize treatment it is relevant to investigate this issue further. Optical Doppler tomography is capable of measuring blood flow in biological tissue down to 1-2 mm with sub-mm/s velocity sensitivity and micrometer spatial resolution making it suitable for blood flow measurements in the skin. We demonstrate the ability of detecting blood flow in the human skin using non-interstitial ODT to preserve the non-invasiveness. In general a very limited blood flow activity was observed in normal skin and around skin tumors making monitoring of changes difficult. We suggest solutions to a number of practical issues such as sampling errors and natural fluctuations in flow activity for future work.
|
|
| 8. |
- Torp-Pedersen, Christian, et al.
(författare)
-
A randomised trial of a pre-synaptic stimulator of DA(2)-dopaminergic and alpha(2)-adrenergic receptors on morbidity and mortality in patients with heart failure
- 2008
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 10:1, s. 89-95
-
Tidskriftsartikel (refereegranskat)abstract
- Background: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). Methods: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. Results: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. Conclusion: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.
|
|
| 9. |
|
|
| 10. |
- Zeggini, Eleftheria, et al.
(författare)
-
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
|
|
