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41.
Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET) 总被引:2,自引:2,他引:0
John M. Bolster Willem Vaalburg Anne M. J. Paans Theo H. van Dijk Philip H. Elsinga Jan B. Zijlstra Do A. Piers Nanno H. Mulder Martien G. Woldring Hans Wynberg 《European journal of nuclear medicine and molecular imaging》1986,12(7):321-324
To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma. 相似文献
42.
Tudor Kate Maloney Shannon Raja Anam Baer Ruth Blakemore Sarah-Jayne Byford Sarah Crane Catherine Dalgleish Tim De Wilde Katherine Ford Tamsin Greenberg Mark Hinze Verena Lord Liz Radley Lucy Opaleye Emerita Satiro Taylor Laura Ukoumunne Obioha C. Viner Russell Kuyken Willem Montero-Marin Jesus 《Prevention science》2022,23(6):934-953
Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such... 相似文献
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Martijn Felder Hester van de Bovenkamp Willem Jan Meerding Antoinette de Bont 《Health policy (Amsterdam, Netherlands)》2021,125(1):34-40
We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives. 相似文献
45.
Laure F. Pittet Marc Tebruegge Binita Dutta Susan Donath Nicole Messina Dan Casalaz Willem A. Hanekom Warwick J. Britton Roy Robins-Browne Nigel Curtis Nicole Ritz 《Vaccine》2021,39(4):652-657
BackgroundBacillus Calmette–Guérin (BCG) vaccine provides partial protection against Buruli ulcer caused by Mycobacterium ulcerans in epidemiological studies. This study aimed to quantify M. ulcerans-specific immune responses induced by BCG immunisation.MethodsIntracellular cytokine analysis of in-vitro experiments done 10 weeks after BCG immunisation in 130 Australian infants randomised to one of three BCG vaccine strains given either at birth (BCG-Denmark, BCG-Japan, or BCG-Russia) or at two months of age (BCG-Denmark).ResultsProportions of polyfunctional CD4+ T-cells were higher in M. ulcerans-stimulated compared to unstimulated control samples. These proportions were not influenced by the vaccine strain or timing of the immunisation. The M. ulcerans-specific immune responses showed similar patterns to those observed in M. tuberculosis-stimulated samples, although they were of lower magnitude.ConclusionsOur data show that BCG immunisation induces M. ulcerans-specific immune responses in infants, likely explaining the cross-protective effect observed in epidemiological studies. (ACTRN12608000227392) 相似文献
46.
The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 g/kg body weight and the high-dose group (15 animals) 0.80–1.20 g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 g/l after 70 days and in the high-dose group to ca. 900 g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 g lead/l blood no adverse effects were observed that did occur at the high dose level.Part 2, dealing with the histopathology and (electron) microscopy of the kidneys is in preparation 相似文献
47.
Edna H. G. Venneker Willem J. Remme MD PhD Diederik C. A. van Hoogenhuyze X. Hanno Krauss G. Louis Bartels Dick A. C. M. Kruijssen Cock J. Storm Dick van Schelven 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1994,8(2):211-219
Summary Antiischemic effects of 1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial 1-agonistic activity, although useful in preserving cardiac function, may counteract such antischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective 1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p<.05), whereas cardiac output fell temporarily by 9% (p<.05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p<.05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16±7% vs. –7±8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p<.05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional 1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its 1-antagonistic profile. 相似文献
48.
Alexander Sparreboom Manon T. Huizing Jan J. B. Boesen Willem J. Nooijen Olaf van Tellingen Jos H. Beijnen 《Cancer chemotherapy and pharmacology》1995,36(4):299-304
Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1–3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was >97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and 6,3-p-dihydroxypaclitaxel. The two 6-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmockinetics studies. 相似文献
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Hugo J. Van Staveren Hans P. A. Marijnissen Maurice C. G. Aalders Willem M. Star 《Lasers in medical science》1995,10(2):137-147
Spherical isotropic fibre optic light diffusers are used in photodynamic therapy either as a light source or as a light detector. The construction of light diffusers using different materials is described, viz. an optical method involving local polymerization of a dental fissure sealant, which is referred to as the Henderson method, and a second method using plastic or ceramic pre-fabricated spheres. Quality tests necessary for reliable clinical use are presented for the mechanical strength, output power and isotropy. The maximum pull-off force and blow-off output power for the different kinds of diffusers were determined. The calibration procedures are given for measurement of the output power and wavelength of the light emitted by a diffuser and for measurement of the fluence rate by a light-detecting diffuser, using a compact integrating sphere device. With all types of diffusers described, an isotropy can be obtained of better than ± 20% measured over a 320° angle for spheres as small as 1 mm. Larger ceramic diffusers are particularly suitable for delivering high output powers. A 3-mm-diameter ceramic diffuser mounted on a 600-m-core fibre can emit up to 5 W of continuous wave (CW) visible light in air. Diffusers used for light detection can measure the light fluence rate in tissue with 15% accuracy or better if calibration factors are determined for each individual probe. 相似文献