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  • 1
    ISSN: 1468-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent data in the literature indicate that antigen-presenting cells (APC) are inactive in tumour tissue because of local immunosuppression. Tumour-infiltrating lymphocyte (TIL) signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF) may lead to APC recovery and interleukin (IL)-2 may restore local TIL activation. Moreover, IL-2 increases the systemic lymphocyte population, an event that seems to correlate with a better prognosis.〈section xml:id="abs1-3"〉〈title type="main"〉Study designThe present phase I–II study was carried out to examine whether intralesional injection of GM-CSF followed by subcutaneous IL-2 would induce a clinical response in advanced, pretreated elderly melanoma patients.〈section xml:id="abs1-4"〉〈title type="main"〉MethodsSixteen patients over 60 years of age received intralesional GM-CSF (150 ng per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous IL-2 (3 000 000 IU) for 5 days (days 3–7 inclusive) every 3 weeks.〈section xml:id="abs1-5"〉〈title type="main"〉ResultsFour clinical responses [two partial (PR) and two minimal (MR)] (25%), which also involved lesions that had not been directly treated, and nine cases of stable disease were observed. The response duration for PR and MR was 9, 4, 4 and 2.5+ months, respectively. Stable disease (56%) recorded in the nine patients was short-term (3–6 months). Three patients rapidly progressed after two, two and one therapy cycles, respectively. The patient who reached the best PR had a fairly high absolute lymphocyte count (1600–2400/mm3). The second one, who reached complete remission after subsequent locoregional chemotherapy and hyperthermia, however, had a low absolute lymphocyte count that had doubled by the end of treatment. Blood lymphocyte values in the other patients were too varied to allow any correlation with clinical response. Therapy was well tolerated and only mild fever was observed, with the exception of one patient who had grade 3 fever, with muscle pain and arthralgia.〈section xml:id="abs1-6"〉〈title type="main"〉ConclusionsConsidering the very low toxicity observed, this treatment might be indicated in elderly patients for whom systemic therapy is no longer a viable option. Improved scheduling and timing could result from further studies.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Stochastic environmental research and risk assessment 12 (1998), S. 1-14 
    ISSN: 1436-3259
    Keywords: Key words: Exceedance probability ; trend ; stochastic variables ; non-stationarity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Energy, Environment Protection, Nuclear Power Engineering , Geography , Geosciences
    Notes: Abstract Studying the hypothetical case of a trend superimposed on a random stationary variable, we highlight the strong influence of possible non-stationarities on exceedance probability. After a general outline, the subject is analytically developed using the Gumbel distribution, emphasizing the quick increase of the exceedance probability over time in the presence of weak rising trends, and its sensitive underestimation where the non-stationarity goes unnoticed or is considered negligible. Finally the work is applied to hydrological series of rainfall and river flow.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1238
    Keywords: Key words Acquired ATIII deficiency ; ATIII replacement therapy ; Septic shock
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study. Methods: 120 patients admitted to the ICU with an ATIII concentration 〈 70 % were randomized to receive ATIII (total dose 24 000 units) or placebo treatment for 5 days; 56 patients had septic shock. Results: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97–102 %). The Kaplan- Meier analysis showed no difference in overall survival between the two groups: 50 and 46 % for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1 % increase in the ATIII plasma concentration at baseline. Conclusions: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2277
    Keywords: Key words Donor age ; Pediatric donors ; Pediatric kidneys ; Renal transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia-Romagna and Piemonte) over an 11-year period. A group of pediatric donors ( 〈 15 years old, n = 30) was compared with an adult donor group (n = 67). All recipients were adults who received cyclosporin as immunosuppression. Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96 % and 96 % for pediatric donors versus 98 % and 92 % for adult donors at 1 and 5 years post-transplantation; graft survival 76 % and 68 % for pediatric donors versus 88 % and 74 % for adult donors 1 and 5 y post-transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2277
    Keywords: Key words Aortic segment ; Implantation ; Anti-HLA antibody ; Aortic wall thickness ; PRA-STAT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1–3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2277
    Keywords: Key words Organ procurement ; Organ transplantation ; Procurement programme efficiency ; Transplant Programe efficiency ; Evaluation indexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The number of donations per million population (pmp) per year and the number of transplants pmp/year enables one to compare donation or transplant programs made in different years in the same area or made the same year in different areas. These pmp indexes may be integrated with an evaluation system by which each organ is evaluated separately in terms of the efficiency of its procurement and transplant systems using the procurement index (percentage in terms of number of organs utilized/number of organs procurable from donors utilized in a single area during 1 year) and the transplant index (percentage in terms of number of transplants performed/number of organs harvested in a single area during 1 year). We have called them Caldes I (procurement) and Caldes II (transplant) indexes. The harvest index evaluates the efficiency of utilization of organs retrieved from suitable donors. It usually ranges between 80–90 % for the kidney, 70–95 % for the liver, 40–50 % for the heart, and 5–15 % for the lungs. The transplant index evaluates for each organ the transplant team capacity to use available organs which can be harvested locally or in different areas. It usually ranges between 60–120 %. Index determination did not require information different from the standard data available. Both the harvest and transplant indexes could be used to compare the efficiency of donation and transplant programs and policies in the same area during different years or at the same time in different areas. They can be critical in evaluating: (a) marginal donor utilization, (b) marginal organ utilization, and (c) dishomogeneity of organ retrieval and organ transplantation in different regions belonging to the same area. They also enable to evaluate if organs considered not available in a single area are offered to other areas or are not retrieved at all from available donors.
    Type of Medium: Electronic Resource
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