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41.
H. Isoniemi J. Ahonen B. Eklund K. Höckerstedt K. Salmela E. von Willebrand P. Häyry 《Transplant international》1990,3(2):92-97
We have investigated the impact of triple drug immunosuppression on the occurrence of early inflammatory episodes, as detected by fine needle aspiration biopsy, and of episodes of clinical rejection during the immediate postoperative period. The prospective component of this study includes 128 consecutive first cadaveric renal transplant recipients receiving triple drug treatment consisting of azathioprine (Aza), cyclosporin (CyA) and methylprednisolone (MP). For controls we have used three historical groups: one immunosuppressed with Aza and MP (group A), another with CyA monotherapy (group B), and the third with CyA together with MP (group C) in equivalent drug dosages. On the average, 0.8 episodes of inflammation per patient were recorded during the immediate postoperative period of 30 days with triple drug treatment. This was significantly less than the 1.3 episodes in patients receiving Aza and MP (P<0.01), the 1.7 episodes in patients on CyA monotherapy (P<0.001), or the 1.6 episodes in patients receiving CyA together with MP (P<0.001). Although the first episode of inflammation commenced concurrently in each group and the peak intensity of inflammation was the same, the mean duration of inflammation was significantly shorter-2.7 days-under triple drug treatment than the 7.8–11.7 days for controls (P<0.001). The frequency of rejection episodes under triple treatment was also significantly lower-0.2 per patient-than the 0.8 per patient in controls (P<0.001). The first rejection episode occurred later in the triple drug treatment group-on the average, on day 15.2-than in the historical controls (on days 7.7–11.7). There was, however, no difference in the duration of rejection. There were no differences in patient survival between the four groups. Graft survival was 97% at 10 weeks for triple drug-treated recipients and 79%, 68%, and 87% for first grafts in groups A, B, and C, respectively. Disregarding a minor demographic bias for the triple drugtreated group with respect to preformed antibodies and preoperative dialysis treatment, the study suggests that the triple drug protocol, in the short run, is superior to any conceivable double drug combination or CyA monotherapy. 相似文献
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Vivian E. von Gruenigen M.D. Joseph T. Santoso M.D. Robert L. Coleman M.D. Carolyn Y. Muller M.D. David Scott Miller M.D. J.Michael Mathis Ph.D. 《Gynecologic oncology》1998,69(3):197-204
Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100dose of 1 × 107cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 108pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 108pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy. 相似文献
44.
Nicole von Steinbüchel 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,123(1-2):220-233
The organization of the time frames for perceiving, generating, and updating information in the CNS has as of yet received
little attention despite its elementary character for human behavior. We investigated temporal epochs in perceiving, acting,
and updating in patients with anterior and posterior lesions of the left and right hemisphere, in patients with lesions in
the left hemisphere without aphasia, and in healthy controls. Three temporal ranges, 30, 300, and 3000 ms, were assessed with
different psychophysical paradigms. Prolongation of the temporal perception of order (30 ms) was most pronounced with left
posterior lesions, of repetitive action (300 ms) with left anterior lesions, and updating (3000 ms) with left and right anterior
lesions. Temporal deficits are group as well as parameter specific. Our results support the notion of coordinated coexistence
of different temporal mechanisms. 相似文献
45.
In vivo efficacy of azithromycin in treatment of systemic infection and septic arthritis induced by type IV group B Streptococcus strains in mice: comparative study with erythromycin and penicillin G. 下载免费PDF全文
L Tissi C von Hunolstein P Mosci C Campanelli F Bistoni G Orefici 《Antimicrobial agents and chemotherapy》1995,39(9):1938-1947
We compared the activities of azithromycin, erythromycin, and penicillin G in a mouse model of systemic infection and septic arthritis induced by type IV group B streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were analyzed relative to the pharmacokinetics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal drug administration was initiated with different dose regimens at different times after infection. A single dose of azithromycin (100 mg/kg) strongly reduced the incidence of articular lesions with respect to that with erythromycin or penicillin G. Treatment with azithromycin (three intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculated 30 min after infection and at high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin was much more active than erythromycin and penicillin G with respect to bacterial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was employed. The pharmacokinetics of azithromycin account for its superior in vivo efficacy against type IV GBS. A longer half-life and higher levels of this drug in serum and tissues with respect to those for erythromycin or penicillin G were achieved. The high affinity of azithromycin for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestation of GBS infection. 相似文献
46.
Armin W. Geiger M.D. F.I.C.A. Alexander M. Zarubin Ph.D. Marc Hertel Anke Fahrenkamp M.D. Gert von Bally Hans H. Scheld M.D. F.I.C.A. 《The International journal of angiology》1995,4(1):46-50
Dysfunction of heart valve prostheses—mechanical as well as biological—is a common problem in cardiac surgery. The reasons for the valve failures are still not well understood. Biological valves especially have an unsatisfactory durability; degeneration and calcification very often lead to the failure of the valves. In our opinion, hidden defects present in the valve material prior to implantation of the valves is a plausible explanation for the dysfunction. Hitherto there has been no technique to detect these defects without destructing the specimen. Holographic interferometry proved to be applicable forin vitro evaluation of mechanical heart valve prostheses. In the present paper we describe application of this method to biological valves. Nine porcine bioprostheses and four fresh porcine aortic valves were investigated by means of holographic interferometry. In eight of nine bioprostheses, the results showed irregularities of the leaflet structure which depend on anomalies of the connective tissue of the leaflets of the valves. To make sure that these findings are not due to normal variations of the morphology, the investigations were carried out with fresh and unfixated porcine aortic valves. In the latter, no such anomalies of the structure were detected. The results obtained confirm the above hypothesis on the origin of the later valve dysfunction. Thus, holographic interferometry tests of bioprostheses prior to their implantation prevent the use of potentially dysfunctional valves.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993 相似文献
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49.
M. Jung E. Krämer M. Grzenkowski K. Tang W. Blakemore A. Aguzzi K. Khazaie K. Chlichlia G. von Blankenfeld H. Kettenmann J. Trotter 《The European journal of neuroscience》1995,7(6):1245-1265
Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction. 相似文献
50.
Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH. 相似文献