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  • 1
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; MODEL ; MODELS ; THERAPY ; CT ; IMAGES ; VOLUME ; POPULATION ; RISK ; RISKS ; TISSUE ; radiation ; INDUCTION ; PROTON ; AGE ; chemotherapy ; SWEDEN ; BEAM ; treatment planning ; TARGETS ; CHILDREN ; IMRT ; proton therapy ; CHILDHOOD ; CRANIOSPINAL IRRADIATION ; DOSE DISTRIBUTIONS ; intensity ; SURVIVORS ; SOCIETY ; 3D ; complication ; CT images ; BEAMS ; CHILDHOOD MEDULLOBLASTOMA ; 2ND MALIGNANT NEOPLASMS ; PEDIATRIC TUMORS
    Abstract: Aim. The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy ( IMET) and proton therapy (IMPT). Material and methods. CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Results. Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. Conclusion. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative
    Type of Publication: Journal article published
    PubMed ID: 16165914
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  • 2
    Keywords: DISEASE ; kidney ; TRIAL ; HEALTH ; OUTCOMES ; METAANALYSIS ; RENIN-ANGIOTENSIN SYSTEM ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIANTS ; D SUPPLEMENTATION
    Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH) D concentration was associated with decreased systolic blood pressure (beta per 10% increase, -0.12 mm Hg, 95% CI -0.20.to -0.04; p=0.003) and reduced odds of hypertension (odds ratio [OR] 0.98, 95% CI 0.97-0.99; p=0.0003), but not with decreased diastolic blood pressure (beta per 10% increase, -0.02 mm Hg, -0.08 to 0.03; p=0.37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0.10 mm Hg in systolic blood pressure (-0.21 to -0.0001; p=0.0498) and a change of -0.08 mm Hg in diastolic blood pressure (-0.15 to -0.02; p=0.01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0.98, 0.96-0.99; p=0.001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH) D concentration was associated with a change of -0.29 mm Hg in diastolic blood pressure (-0.52 to -0.07; p=0.01), a change of -0.37 mm Hg in systolic blood pressure (-0.73 to 0.003; p=0.052), and an 8 1% decreased odds of hypertension (OR 0.92, 0.87-0.97; p=0.002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
    Type of Publication: Journal article published
    PubMed ID: 24974252
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  • 3
    Keywords: ENERGIES ; OPTIMIZATION ; radiotherapy ; COMBINATION ; LUNG ; THERAPY ; ALGORITHM ; TOOL ; TISSUE ; HEART ; radiation ; PATIENT ; treatment ; PROTON ; WATER ; BREAST ; TARGET ; DISTRIBUTIONS ; RADIATION-THERAPY ; ENERGY ; SWEDEN ; ELECTRON ; BEAM ; NORMAL TISSUE ; SELECTION ; IMRT ; Monte Carlo ; MONTE-CARLO ; intensity modulated radiation therapy ; PHOTON BEAMS ; TARGET COVERAGE ; SEGMENT ; THERAPIES ; DOSE DISTRIBUTIONS ; intensity ; BEAM THERAPY ; COLLIMATION ; conformal therapy ; electrons ; FLUENCE ; radiation therapy ; TREATMENT HEAD DESIGN
    Abstract: Background and purpose: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. Materials and methods: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. Results: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. Conclusions: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart. (C) 2004 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15542170
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  • 4
    ISSN: 1573-8744
    Keywords: interoccasion variability ; interindividual variability ; intraindividual variability ; pharmacokinetics ; population analysis ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Individual pharmacokinetic parameters may change randomly between study occasions. Analysis of simulated data with NONMEM shows that ignoring such interoccasion variability (IOV) may result in biased population parameter estimates. Particular parameters affected and the extent to which they are biased depend on study design and the magnitude of IOV and interindividual variability. Neglecting IOV also results in a high incidence of statistically significant spurious period effects. Perhaps most important, ignoring IOV can lead to a falsely optimistic impression of the potential value of therapeutic drug monitoring. A model incorporating IOV was developed and its performance in the presence and absence of IOV was evaluated. The IOV model performs well with respect to both model selection and population parameter estimation in all circumstances studied. Analysis of two real data examples using this model reveals significant IOV in all parameters for both drugs and supports the simulation findings for the case that IOV is ignored: predictable biases occur in parameter estimates and previously nonexistent period effects are found.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The usefulness of Western blot in the serological diagnosis of Lyme borreliosis was evaluated compared with an ELISA using a whole cell sonicate antigen. Fifty-three of 68 (78 %) patients with neuroborreliosis had positive IgM and/or IgG immunoblots and 40 of 68 (59 %) had positive IgM and/or IgG ELISA titers in serum. Eight of 44 (18 %) controls with meningitis/encephalitis of non-borrelia etiology had positive IgM and/or IgG immunoblots and 4 of 44 (9 %) had positive IgM and/or IgG ELISA titers in serum. Western blot was more sensitive than ELISA, the difference being most pronounced in sera from patients with neurological disease for four weeks or less. Both patients and controls lived in an area endemic for Lyme borreliosis and some ELISA negative but Western blot positive controls were thought to have been previously exposed toBorrelia burgdorferi. However, the specificity for current disease was not improved by Western blot. In conclusion, Western blot does not seem to be the method of choice for screening purposes in a routine laboratory but can be used as a complement to ELISA for serodiagnosis in patients with disease of short duration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum and cerebrospinal fluid (CSF) samples from four patients with Lyme neuroborreliosis were analyzed for IgM and IgG antibodies by an indirect enzyme immunoassay with the four patients' own CSF isolate ofBorrelia burgdorferi and two tick isolates, strains STG152 and B31, as antigens. No major differences in the antibody response were found comparing autologous and heterologous strains as sonicate antigens, although a tendency towards a stronger response to the autologous isolates was noted in samples from two patients.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A sonicate antigen and two concentrations of a purified flagellum antigen ofBorrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13 % in the sonicate EIA to 31 % in the best flagellum EIA assay (p=0.01) in sera from patients with erythema migrans (n=70), and from 34 % to 55 % (p=0.01) in sera from patients with neuroborreliosis (n=77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n=20) was high in both assays: 90 % in the sonicate EIA compared to 95 % in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non-Borrelia etiology (n=35), multiple sclerosis (n=9) or syphilis (n=24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p〈0.01). It is concluded that purifiedBorrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1437-1596
    Keywords: Drugs, in biological samples ; drinking drivers, drugs in urine ; blood alcohol and drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Für die qualitative und quantitative Analyse von Arzneimitteln in biologischem Material wurde nach Extraktion mit Heptan-Isoamylalkoholgemisch die kombinierte Anwendung von Dünnschicht- und Gaschromatographie entwickelt. Sowohl basische als auch saure Extraktion wurde durchgeführt, darüberhinaus für Salycilate, Isoniazid und Morphin spezielle Extraktionsmittel verwendet. Besonders wurde auf Psychostimulantien geachtet, die bei Kraftfahrern unter Alkohol in Finland nur selten nachweisbar sind, relativ häufig jedoch in Schweden auftreten. Bei etwa 2% aller Kraftfahrer, die einer Blutprobe zugeführt wurden, war Arzneimitteleinfluß vermutet worden, was zur Asservierung einer Urinprobe führte. Von 100 dieser Delinquenten hatten 24 keinen Alkohol im Blut, bei 18 von diesen 24 ließen sich Arzneimittel in der Urinprobe nachweisen. 76 von diesen 100 Kraftfahrern wiesen jedoch auch relevante Blutalkoholwerte auf, bei 25 dieser 76 ließen sich ebenfalls Arzneimittel im Urin nachweisen. Von 100 zufällig ausgewählten, unter dem Verdacht der Alkoholbeeinflussung festgenommenen Kraftfahrern verlief bei 5 der Arzneimittelnachweis im Urin positiv, 4 von diesen 5 hatten ebenfalls Alkohol im Blut. Benzodiazepine waren die am häufigsten nachweisbaren Arzneimittel, jedoch konnten in unserem Material keine Psychostimulantien gefunden werden.
    Notes: Summary A combined thin layer and gas chromatography system was developed for qualitative and quantitative analysis of drugs in biological samples after extraction with heptane-isoamyl alcohol. Both acidic and basic extraction procedures were used. Special methods were used for the extraction and detection of salicylates, isoniazid, and morphine. Particular attention was given to the detection of psychostimulants; though these drugs have seldom been found in drinking drivers in Finland they are commonly found in Sweden. Two percent of all suspected drinking drivers were also suspected of concommitant drug use, which led to primary sampling of urine. Of 100 such drivers, 24 had blood alcohol levels (BALs) which were negative and 18 of that 24 had drugs in their sample. Seventysix of the 100 had positive BALs and 25 of the 76 had drugs in their samples. Of the randomly chosen 100 suspected drinking drivers, 5 had drugs in their samples, and 4 of these 5 had positive BALs. The benzodiazepines were the most commonly detected drugs. No stimulants were found in our subjects.
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  • 9
    ISSN: 1437-1596
    Keywords: Anileridine, Gas chromatography-Mass spectrometry ; Pethidine, Gas chromatography-Mass spectrometry ; Poisoning, Anileridine, Pethidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Anileridin und Pethidin wurden mittels Gas- und Dünnschicht-chromatographie sowie massenspektroskopisch festgestellt. Im Massenspektrum liegen die Hauptspitze von Anileridin bei m/e 246 und diejenige von Pethidin bei m/e 71. Die Bestimmung erfolgte gaschromatographisch aus Blut, Harn, Leber, Muskel und Mageninhalt.
    Notes: Summary Anileridine and pethidine were established by gas and thin layer chromatography and mass spectroscopy. In the mass spectrum the main peak of anileridine is found at m/e 246 and that of pethidine at m/e 71. The determination was made by gas chromatography from the blood, urine, liver, muscle and stomach contents.
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  • 10
    ISSN: 1432-0827
    Keywords: Weight lifters ; Athletes ; Bone turnover ; Osteocalcin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Physical activity has been suggested to be one of the determinants of bone turnover and to prevent age-related bone loss. To examine this we measured the serum levels of osteocalcin (bone Gla-protein, BGP), C-terminal procollagen peptide (PICP), serum alkaline phosphatase, bone-specific alkaline phosphatase, and S-calcium as indices of bone formation in 19 actively performing and 15 ex-lifters. All were nationally or internationally ranked male athletes. Their values were compared with those from 38 age- and gendermatched controls. Actively performing weight lifters had 35% higher (P〈0.05) serum concentration of osteocalcin than the controls. The ex-lifters did not differ from the agematched controls. Also serum calcium was elevated in active lifters (6%) (P〈0.01) but not in ex-lifters. No difference was found for serum-ALP, B-ALP, or PICP in either of the groups. Our study indicates that in addition to an already documented and well-known higher bone mineral density in heavily exercising athletes, they have an indication of higher bone formation as measured by biochemical markers. In athletes who have retired from competitional training, however, the bone formation does not differ from that of more sedentary controls.
    Type of Medium: Electronic Resource
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