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81.
Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies 总被引:1,自引:0,他引:1
Marian A. B. D. Plaizier Jan C. Roos Gerrit J. J. Teule Erik B. van Dieren Wim den Hollander Hidde J. Haisma Robert L. DeJager Arthur van Lingen 《European journal of nuclear medicine and molecular imaging》1994,21(3):216-222
Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium- 111-OV-TL-3 F(ab)2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111 In-OV TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16-88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.
Correspondence to: M.A.B.D. Plaizier 相似文献
82.
This paper presents a 7-12 year (mean 9.8 years) follow-up of 92 extremely obese patients treated with Marlextrade mark mesh gastric banding (GB). The follow-up rate was 92% (85 patients). Weight loss was initially good (an average reduction in BMI of 13 during the first year), but late weight gain has been a common complaint and a reason for reoperation. Other complications that necessitated reoperation were severe vomiting and esophagus not amenable to medical treatment. Four patients have developed signs of Barrett's esophagus at late follow-up. Forty-six patients (50%) were reoperated 70 times for correction of the band or conversion to vertical banded gastroplasty (VBG). The most common reoperative procedure was conversion to VBG (38 patients). Only 25 (31%) of the 80 patients with long-term follow-up have an intact band. Our results show the need of long follow-up and that this GB cannot be recommended for the treatment of morbid obesity. 相似文献
83.
The effects of caffeine on cytoplasmic Ca2+ oscillations induced by carbachol and guanosine 5-O-(3-thiotriphosphate) (GTP--S) were studied in individual mouse pancreatic ß-cells clamped at a hyperpolarized potential. Addition of 10 mM caffeine did not affect the cytoplasmic Ca2+ concentration ([Ca2+]1) in ß-cells exposed to 20 mM glucose and hyperpolarized with diazoxide. Under similar conditions 100 M carbachol induced a typical response with a marked [Ca2+]i peak followed by a lower sustained elevation. Irrespective of whether 10 mM caffeine was present, there were [Ca2+]i transients with frequencies of 1–5/min superimposed on the sustained phase in 50–60% of the cells. In previously non-exposed cells the introduction of 10 mM caffeine caused temporary lowering of the sustained phase with disappearance of the transients. Subsequent omission of caffeine in the continued presence of carbachol caused a marked [Ca2+]i peak followed by reappearance of the [Ca2+]i, transients. However, in cells oscillating in the presence of caffeine its omission caused disappearance of the transients. In this case reintroduction of caffeine restored the transients.In cells kept at –70 mV by a patch pipette containing 100 M GTP--S and 3 mM Mg-ATP there were [Ca2+]i transients with frequencies of 0.5–2.5/min. These transients were sufficiently pronounced to activate repetitively a K+ current. Addition of 10 mM caffeine caused disappearance of the [Ca2+]i transients or reduction of their amplitudes and frequencies.The results indicate that caffeine does not activate Ca2+-induced Ca2+ release in hyperpolarized ß-cells but inhibits the Ca2+-mobilizing effect of inositol 1,4,5-trisphosphate.
Correspondence to: E. Gylfe at the above address 相似文献
84.
Bernd Mühlbauer Erik Hartenburg Hartmut Osswald 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(3):244-249
Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (UDA) in conscious rats (Mühlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and UDA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33±7% (P<0.001) and UDA by 87±19% (P<0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 g/min/kg, UDA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA1 receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 g/kg/min did not prevent the AA-induced increase in GFR (33±3%, P<0.001) and UDA (97±12%, P< 0.001). In contrast, S-sulpiride (SUL), a specific DA2 receptor antagonist, infused continuously i.v. in a dose of 5 g/kg/min, completely abolished the AA-induced GFR increase, while UDA was increased 1.6-fold (P<0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially.Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA2 receptors.
Correspondence to:B. Mühlbauer at the above address 相似文献
85.
86.
Erik Nord 《Health care analysis》1999,7(2):167-175
By describing societal value judgements in health care in numerical terms one may in theory increase the precision of guidelines
for priority setting and allow decision makers to judge more accurately the degree to which different health care programs
provide societal value for money. However, valuing health programs in terms of QALYs disregards salient societal concerns
for fairness in resource allocation. A different kind of numerical valuation of medical interventions, that incorporates concerns
for fairness, is described. The usefulness to decision makers of such numerical information remains to be tested.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
87.
The purpose of the present study was to observe recovery of orienting deficits during unilateral and bilateral cooling inactivation of the middle suprasylvian (MS) cortex. Unilateral MS cooling resulted in a contralateral hemineglect (no orienting responses towards stimuli in the contracooled hemifield) that spontaneously recovered within less than 40 min of continued cooling. Moreover, the brain changes responsible for this recovery were partially retained and cumulated over successive cooling days. Bilateral MS cooling indicated that recovery of neglect can be induced by a restoration of the imbalance between activity levels of structures in both hemispheres and revealed an interaction between spontaneous and induced recovery of neglect. These results show that considerable changes may occur in the brain during cooling for rather short periods. Possible explanations for these changes are discussed. 相似文献
88.
Leonie J. M. Rijks Gerard J. Boer Erik Endert Kora de Bruin Jan C. van den Bos Peter A. P. M. van Doremalen Willem G. E. J. Schoonen Anton G. M. Janssen Eric A. van Royen 《European journal of nuclear medicine and molecular imaging》1996,23(3):295-307
We studied the potential of both stereoisomers of 17-[123I]iodovinyloestradiol (E- andZ-[123I]IVE) and of 11-methoxy-17-[123I]iodovinyloestradiol (E-andZ-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their123I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[123I]MIVE being higher than that ofE- andZ-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher forE-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [123I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[123I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted. 相似文献
89.
Summary A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benzimidazole. Several of these compounds were found to inhibit L1210 cell proliferation with an ID50 (50% inhibitory dose) of 1 g/ml or lower. Structure-function analysis revealed that the antitumor cell activity of the diarylamidines depended on the planarity of the molecule, the presence of amidino- (or, preferably, imidazolino-) groups on both aryl moieties, the nature of the bridge connecting the two aryl moieties (preferably no bridge at all, phenoxy or ethene) and, finally, the nature of the aryl moieties (preferably, benzofuran or benzo[b]thiophene). Hence, compound 20 (6-(2-imidazolin-2-yl)-2-[4-(2-imidazolin-2-yl)phenyl] benzo[b]thiophene) emerged as the most potent inhibitor of L1210 cell growth (ID50: 0.21 g/ml). Its inhibitory potency was similar to that of the well-known trypanocidal drug ethidium bromide (compound 98). For all diarylamidine derivatives taken together, some correlation (r = 0.612) was noted between the log ID50 for L1210 cell proliferation and the log ID50 for L1210 cell DNA synthesis (as monitored by [methyl
3H]dThd incorporation). These findings suggest that the inhibitory effects of the diarylamidines on L1210 cell proliferation may at least partially reside in an inhibition of DNA synthesis. Compound 41 (2,2-vinylenedi-1-benzofuran-5-carboxamidine), that exhibited a potent antitumor activity in vitro (ID50: 1.5 g/ml), was further evaluated for its antitumor efficacy in vivo and found to increase the median survival time of L1210 cell-inoculated BDF1 mice up to 204%, if administered at a dose of 200 mg/kg. 相似文献
90.
Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer 总被引:2,自引:0,他引:2
Preben Jakobsen Eva Steiness Lars Bastholt Mads Dalmark Anders Lorenzen Dorthe Petersen Susanne B. Gjedde Erik Sandberg Carsten Rose Ole S. Nielsen Henning T. Mouridsen Anders Jakobsen 《Cancer chemotherapy and pharmacology》1991,28(1):63-68
Summary Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (meant
1/2, 21.6±7.9 h; range, 10.6–69 h;n=110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (meant
1/2, 18.1±4.8 h; range, 8.2–38.4 h;n=105).Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (meant
1/2, 13±4.6 h; range, 2.7–29 h;n=104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC=9.44×c
2+62.5×c
24+157.7 (r=0.953).This work was supported by the Lundbeck Foundation, the Michaelsen Foundation and Farmitalia Carlo Erba Ltd. 相似文献