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1.
Ferry Verbaan Inger van Dam Yoshinubu Takakura Mitsuru Hashida Wim Hennink Gert Storm Christien Oussoren 《European journal of pharmaceutical sciences》2003,20(4-5):419-427
The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs. 相似文献
2.
Coronary revascularization using percutaneous coronary intervention (PCI) has rapidly developed in the past 2 decades and its technical and pharmaceutical improvements may avoid bypass surgery in many situations. The use of drug-eluting stents (DES) challenges the classic indications for bypass surgery and shifts them toward PCI, with the need for a critical appreciation of procedure- and patient-related risks. Furthermore, invasive measures such as intravascular ultrasound or pressure wire allow lesion-specific and immediate therapeutic decisions. This overview summarizes the actual potential of coronary intervention. To be aware of potentials and limitations may help the non-interventionalist to advise his patient and to choose the appropriate treatment. 相似文献
3.
4.
This study presents a first assessment of the challenges faced by Dutch health care providers dealing with the increasing cultural diversity in Dutch society. Qualitative interviews with 24 Dutch caregivers and policy-makers point to a number of important difficulties encountered when confronted with the growing diversity of patient populations. The study focuses explicitly on the challenges health care providers perceive in their direct interactions with patients. On the basis of the observations of the 24 respondents five strategies were formulated to improve the delivery of care in a multicultural environment. Their findings were further evaluated by confronting the empirical data with care-ethical notions (attentiveness, responsibility, competence, and responsiveness) and intercultural communication-theory. 相似文献
5.
Priv.-Doz. Dr. Andreas Dávid Axel Ekkernkamp Gert Muhr 《Operative Orthopadie und Traumatologie》1994,6(3):196-207
Operationsprinzip Korrektur eines Pes equinus adductus durch keilf?rmige Resektion des Chopart-Gelenkes mit Keilbasis dorsolateral. Bei gleichzeitigem
Pes varus keilf?rmige Resektion des subtalaren Gelenkes mit Keilbasis lateral (Lange 1962 [7], Myerson et al. 1986 [8], Witt
et al. 1985 [13]) (Abbildungen 1a bis 1f).
Bei gleichzeitigem Tarsaltunnelsyndrom Dekompression des Nervus tibialis durch Spaltung des Retinaculum musculi flexorum.
Zur Korrektur von Krallenzehen Resektion der jeweiligen distalen Grundphalangen nach Hohmann; bei flektierten Endgelenken
Resektion der distalen Mittelphalangen. (Auf diese Techniken wird hier nicht eingegangen).
相似文献
6.
7.
Gert Jan Laarman Menco G. Niemeyer Albert V. G. Bruschke Fred J. Verzijlbergen T. Liam Go Ernst E. van der Wall Carl A. P. L. Ascoop 《European journal of nuclear medicine and molecular imaging》1989,15(5):239-243
To establish test specific normal limits for quantitative analysis of uptake and washout of 201Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of 201Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201Tl derived from healthy volunteers who underwent the same combined protocol. 相似文献
8.
In the past decade, several studies have used scaling and clustering techniques to document semantic storage deficits in patients with Alzheimer's disease and in schizophrenia. In this article the authors argued that many of the conclusions drawn from these studies are unjustified by the data. They reviewed the methodology used in these studies and presented data from simulation studies to further investigate the validity of their conclusions. The authors elaborate on the criteria needed to exclude alternative accounts of the data and present empirical data from patients with Alzheimer's disease and normal control participants to demonstrate that analyses of the patients' proximity data do not provide unambiguous evidence for a generalized semantic storage deficit. 相似文献
9.
Grisk O Lother U Gabriëls G Rettig R 《Pflügers Archiv : European journal of physiology》2005,449(4):364-371
Renal transplantation experiments have shown that the kidney contributes to chronic sympathectomy-induced arterial pressure reduction in spontaneously hypertensive rats (SHR). The underlying mechanisms are currently unclear but may include alterations in the function of small renal arteries. Neonatal SHR were sympathectomized by intraperitoneal guanethidine injections and removal of adrenal medullary tissue. Controls were sham- or hydralazine-treated. At 12 weeks of age, distal interlobar artery segments were investigated using small-vessel wire myography. Vessels from sympathectomized animals showed increased sensitivity to noradrenaline (NE). Vasopressin- and endothelin-1-induced vasoconstriction was similar in all groups (as reflected by the pD2, i.e. –logEC50, where EC50 is the molar concentration of agonist eliciting a half-maximal response). Maximum vasopressin-induced tension was similar in all groups while endothelin-1-induced maximum tension was significantly higher in sympathectomized than in sham-treated SHR. The sensitivity of NE-induced vasoconstriction to extracellular Ca2+ did not differ between groups while sensitivity to L-type Ca2+ channel activation was significantly higher in both sympathectomized and hydralazine-treated animals than in sham-treated animals. Endothelium-dependent and independent vasodilation were similar in all groups. Sequential blockade of NO-synthase and cyclooxygenase had similar effects in all groups. In conclusion, neonatal sympathectomy does not induce any changes in the function of isolated proximal renal resistance arteries from SHR that could explain the blood pressure lowering effect of a kidney graft from sympathectomized SHR. 相似文献
10.
Heterozygote detection in phenylketonuria 总被引:1,自引:0,他引:1
Phenylalanine loading was carried out on 105 parents of children with phenylalanine hydroxylase deficiency and 33 apparently normal individuals with no family history of phenylketonuria. The best discriminant was found to be the logarithmic transformation of the slope of the rise in serum tyrosine multiplied by the maximum serum tyrosine concentration over the maximum serum phenylalanine concentration obtained after an oral load with a pure solution of L-phenylalanine. The overlap between heterozygotes for phenylketonuria and normal homozygotes was 2.4%. The distribution of the discriminant values suggested three heterozygous phenotypes for phenylalanine hydroxylase deficiency, and the phenotypic combination of parents could be correlated to the phenotype of their affected offspring, i.e. classical phenylketonuria, mild phenylketonuria or hyperphenylalaninemia. The probability of heterozygosity for phenylketonuria was determined by means of the distribution of the discriminant values of the heterozygotes and that of normal homozygotes. The likelihood of being a heterozygote was corrected for the genetic background of the person requiring genetic counseling, and was finally expressed as the percentage probability of being a heterozygote for phenylketonuria. 相似文献