369 research outputs found

    The first three years of a neurosis centre

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    Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

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    This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20–41) and 285 days (range 50–1240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients. © 2000 Cancer Research Campaig

    Tectonic denudation and topographic development in the Spanish Sierra Nevada

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    The denudation history of the rapidly uplifting western part of the Spanish Sierra Nevada was assessed using apatite fission track (AFT) ages and 10Be analyses of bedrock and fluvial sediments. Major contrasts in the denudation history are recorded within the 27 km2 Río Torrente catchment. Upland areas are characterized by low-relief, low slope angles, and locally the preservation of shallow marine sediments, which have experienced <200 m of erosion in the last 9 Myr. However, AFT age determinations from samples collected close to the marine sediments imply >2 km of denudation since circa 4 Ma. The minimum denudation rates of 0.4 mm yr−1 derived from AFT also contrast with the slow medium-term (104 years) erosion rates (0.044 ± 0.015 mm yr−1) estimated from 10Be measurements at high elevations. The local medium-long-term contrasts in denudation rates within the high Sierra Nevada indicate that much of the unroofing occurs by tectonic denudation on flat-lying detachments. In lower elevation parts of the catchment, rapid river incision coupled to rock uplift has produced ∼1.6 km of relief, implying that the rivers and adjacent hillslopes close to the edge of the orogen are sensitive to normal-fault-driven changes in base level. However, these changes are not transmitted into the low-relief slowly eroding upland areas. Thus the core of the mountain range continues to increase in elevation until the limits of crustal strength are reached and denudation is initiated along planes of structural weakness. We propose that this form of tectonic denudation provides an effective limit to relief in young orogens

    Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa

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    The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (RĂŠsumĂŠ d'auteur

    Combination chemotherapy with or without s.c. IL-2 and IFN-Îą: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

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    The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m−2, days 1–3), carmustine (150 mg m−2, day 1, cycles 1 and 3 only), dacarbacine (220 mg m−2, days 1–3) and oral tamoxifen (20 mg m−2, daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-α. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10×106 IU m−2, days 3–5, week 4; 5×106 IU m−2, days 1, 3, 5, week 5) and s.c. IFN-α (5×106 IU m−2, day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-α was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively
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