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- Bill-Axelson, Anna, 1965-
(författare)
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Localized Prostate Cancer : Results From a Randomized Clinical Trial
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the thesis were to• explore whether radical prostatectomy is beneficial compared with watchful waiting in survival and disease progression• find possible effect modifiers• evaluate a protocol of multiple biopsies and investigate if men with previous benign prostate biopsies are a group at risk for later prostate cancer• inquire into patients’ and clinicians’ experiences of randomization in order to find out what made this study possible to conduct, and thereby contribute to improve randomization in the futureThe background material was a large randomized clinical trial, the Scandinavian Prostatic Cancer Group Study Number 4, or SPCG-4, which was open for inclusion from February 1989 through December 1999. It comprised 695 men in Sweden, Finland and Iceland who had localized prostate cancer and were randomized to either radical prostatectomy or watchful waiting. After a mean follow-up time of 6.2 years the first analyses, according to intention-to-treat, showed that radical prostatectomy reduced disease specific mortality, risk of metastases and risk of local progression but did not statistically significantly reduce overall mortality. The second analyses confirmed our earlier findings and furthermore, at ten years, radical prostatectomy also statistically significantly reduced overall mortality. Age appeared as an independent effect modifier that will be further investigated.A total of 547 men, with a suspicion of prostate cancer that had undergone multiple biopsies, and whose biopsies had benign histology were later compared with the background population to evaluate whether they were a group at risk of developing prostate cancer. Within six years of follow-up, there was no increased risk of prostate cancer.Patients as well as clinicians used individual strategies to cope with the situation. The randomizing clinician has to understand the patient’s strategy and his expectations in order to individualize the information accordingly.
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- Gahm, Caroline, et al.
(författare)
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Reduced neuronal injury after treatment with NG-nitro-L-arginine methyl ester (L-NAME) or 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) following experimental brain contusion
- 2005
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 57:6, s. 1272-1281
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Nitric oxide (NO) and oxygen free radicals are implicated in the pathophysiology of traumatic brain injury (TBI). Peroxynitrite formation from NO and superoxide contributes to secondary neuronal injury but the neuroprotective effects of nitric oxide synthase (NOS)-inhibitors have been contradictory. This study was undertaken to examine whether PTtic administration of the (NOS)-inhibitor N-nitro-l-arginine methyl ester (L-NAME), and a combination of L-NAME and the nitrone radical scavenger 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) favorable affects neuronal injury in a model of TBI. METHODS: A weight-drop model of TBI was used. The animals received L-NAME, S-PBN or a combination of the drugs 15 minutes prothrombin time (PT) and sacrificed after 24 hours or six days. NOS activity was measured by the conversion of L-[U-C]arginine to L-[U-C]citrulline. Peroxynitrite formation, cellular apoptosis, neuronal degeneration and survival were assessed by nitrotyrosine-, TUNEL-, Fluoro-Jade- and NeuN-stainings. RESULTS: eNOS and nNOS activity was significantly reduced in animals that received L-NAME alone or the combination with S-PBN. iNOS activity or iNOS immunoreactivity was not affected. All treatments significantly reduced neuronal degeneration and nitrotyrosine immunoreactivity at 24 hours and increased neuronal survival at six days PT. No differences were detected between L-NAME and L-NAME + S-PBN groups. CONCLUSION: NO from NOS contributes to secondary neuronal injury in this TBI-model. PTtic treatment does not inhibit early beneficial NO-related effects. L-NAME and S-PBN limit peroxynitrite formation, promoting neuronal survival. The combination of L-NAME and S-PBN was neuroprotective; surprisingly no additive effects were found on nitrotyrosine formation, apoptosis or neuronal survival.
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- Graham, Ian, et al.
(författare)
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European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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- Hosseini, Abolfazl, et al.
(författare)
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Enhanced formation of nitric oxide in bladder carcinoma in situ and in BCG treated bladder cancer
- 2006
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Ingår i: Nitric oxide. - Orlando, Fla. : Academic Press. - 1089-8603 .- 1089-8611. ; 15:4, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to analyze endogenous nitric oxide (NO) formation and NO-synthase (NOS) gene expression in the urinary bladder from patients with urinary bladder cancer and to investigate the relationship between local NO formation, treatment with Bacillus Calmette Guerin (BCG) and clinical stage in bladder cancer patients. One hundred and three patients with bladder cancer were studied. Endogenous formation of NO was measured in 72 patients, including 6 patients with BCG treated bladder cancer and 6 tumor free control subjects. iNOS expression was analyzed at transcriptional and protein level in biopsies from 31 patients with bladder cancer by real time polymerase chain reaction (PCR) and Western blot (WB), respectively. Three patients in this group had received BCG treatment. Eight biopsies from normal bladder served as control for PCR and WB analysis. Patients with carcinoma in situ (CIS) had higher iNOS expression (p<0.01) and NO formation (p<0.01) than control subjects and patients with papillary tumors without concomitant CIS. Markedly increased iNOS expression (p<0.05) and NO formation (p<0.001) were also found in patients treated with BCG as compared to the other groups. In conclusion, the presence of elevated NO concentration and iNOS expression in the urinary bladder from BCG treated patients and patients with CIS further supports the notion that NO may be an important factor in bladder cancer biology and that the BCG effect on superficial bladder cancer may partly be due to stimulation of local NO formation.
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- Kaplan, Alexander, et al.
(författare)
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Imaging in cooperation with modeling of selected defect mechanisms during fiber laser welding of stainless steel
- 2008
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Ingår i: Congress proceedings. - Orlando, Fla : Laser institute of America. - 9780912035123 ; , s. 789-798
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Konferensbidrag (refereegranskat)abstract
- Fiber laser welding of stainless steel was studied for different joint configurations and gaps. The higher focusing capability of fiber lasers compared to traditional Nd:YAG and CO2 lasers creates different, usually smaller, keyhole and melt pool geometries. These geometrical aspects, accompanied by a different laser energy redistribution, are essential for the weld pool dynamics and the resulting joint, with or without defects. Typical defects identified during fiber laser welding were spatter, humping, or lack of material at the top or root. High-speed imaging enables observation of the geometry and motions of the melt pool surface and keyhole during welding. This is illuminated by an additional diode laser permitting spectral filtering and also the metal vapor dynamics can be visualized. Mathematical modeling provides the possibility to estimate and study additional phenomena that are difficult to measure, such as effects inside the melt volume or the impact of surface tension forces on dynamic melt motion. For recorded melt surface motion images, in particular, the corresponding surface tension forces and other mechanisms can be estimated by cooperative complementary modeling, enabling to draw conclusions. This advanced method was carried out for the different joint and defect cases studied, resulting in an illustrated theoretical description of the observed physical phenomena.
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- Menu, Eline, et al.
(författare)
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Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse model of multiple myeloma : beneficial effects on tumor growth, angiogenesis, bone disease and survival
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:8, s. 1857-1861
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Tidskriftsartikel (refereegranskat)abstract
- During the last decade, a central role for insulin-like growth factor 1 (IGF-1) in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I provided by the tumor-microenvironment interaction may directly and indirectly facilitate the migration, survival and expansion of the MM cells in the bone marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently been suggested to be a possible new therapeutic principle in MM. Using the mouse 5T2MM model, we now demonstrate that targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. At therapeutically achievable concentrations of PPP, the average survival was 180 days for the PPP-treated mice as compared to 100 days for vehicle-treated mice. PPP used as single drug treatment in the 5T2MM model resulted in a decrease of tumor burden by 65% while the paraprotein concentrations were reduced by 75%. This decrease was associated with a significant inhibition of tumor-associated angiogenesis and osteolysis. The present studies on the biological effects of PPP in the 5T2MM model constitute an important experimental platform for future therapeutic implementation.
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- Mörner, Stellan, et al.
(författare)
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Parasympathetic dysfunction in hypertrophic cardiomyopathy assessed by heart rate variability: comparison between short-term and 24-h measurements
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:2, s. 90-99
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this study, we evaluate cardiac autonomic function in hypertrophic cardiomyopathy (HCM) by assessing heart rate variability (HRV), comparing a short-term laboratory method with an ambulatory (24-h) method, in patients with and without beta-blockade. Reduced HRV is a risk factor for adverse events in some cardiac diseases, but is not a proven risk indicator in HCM. Analysis of HRV has been based on either short- or long-term electrocardiographic recordings and previous studies in HCM have shown conflicting results. There is no consensus on which method to prefer, and we evaluate, for the first time, both short- and long-term analyses in patients with HCM. Long- and short-term HRV analyses were performed in 43 patients with HCM. They were divided in two groups, 22 patients on beta-blockade and 21 non-treated patients. As controls, 121 healthy subjects were used. Young patients without beta-blockade showed a reduction in HRV parameters reflecting parasympathetic function, both in the short- and long-term registrations, which was attenuated by beta-blockade. Parasympathetic autonomic regulation was found to be impaired in young patients with HCM. This may be of clinical relevance as abnormal autonomic function might be a substrate for malignant dysrhythmias. The impairment was attenuated by beta-blockade, which might indicate a clinically useful effect. We also show that short- and long-term methods yield similar results, suggesting that a short-term registration might be sufficient to assess HRV in patients with HCM.
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