PURPOSE: The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). RESULTS: Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. CONCLUSION: This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases. 相似文献
An ecological epidemiological study was conducted with data obtained from an environmental dose-reconstruction study and the Arizona Birth Information Tapes. Before 1981, a portion of the city of Tucson water-distribution system was contaminated with trichloroethylene (i.e., < 5 micrograms per liter of water to 107 micrograms per liter of water). Target and comparison populations were selected with a Geographic Information System. Logistical-regression analysis revealed an association between maternal exposure to trichloroethylene via drinking water and very-low-birth-weight babies (i.e., < 1,501 grams) (odds ratio = 3.3; 95% confidence interval = 0.5, 20.6; and Wald chi-square p value = 0.2). No association was found between maternal exposure to trichloroethylene via drinking water and low birth weight or full-term low-birth-weight infants (gestational period > 35 wk and < 46 wk). 相似文献
Background and Objectives John Milton Hagen (JMH) antigens are carried by Semaphorin 7A that plays important roles in the nervous system and the immune responses. Its role on the erythrocytes is unclear. Over the years, few samples were referred to our Immunohaematology Reference Laboratory to elucidate their JMH status. Materials and Methods Seven blood samples with antibodies compatible with JMH1‐negative red cells were studied at the molecular level to identify polymorphisms and explain the JMH diversity observed. Four samples were of Native American background and three were Caucasians. Molecular analyses of the SEMA7A were undertaken, and soluble form of recombinant Sema7A proteins was produced to characterize the antibodies. Results Sequencing of the cDNA showed a polymorphism in SEMA7A exon 9 at position 1040 (G>T) in the four Native American samples. Caucasians had a normal sequence. This polymorphism precludes a change at position 347 where an Arg is replaced by a Leu. Plasma was assayed in ELISA on wild‐type Sema7AArg347 and variant Sema7ALeu347 proteins. Results clearly indicated a specific recognition of the antibody produced by the Native Americans for the wild‐type Sema7AArg347 protein and not the variant one. Conclusion A new SEMA7A variant was identified in this study. The antibody present in the Native American plasma samples should be considered as an alloantibody because it recognizes the wild‐type protein. 相似文献
Introduction: CD8+ T lymphocytes (CD8TLs) express β-adrenergic receptors (βAR), which bind the neurotransmitter norepinephrine and stress hormone epinephrine released during inflammation, trauma, and psychological stress. Little is known about the functions of this βAR expression on CD8TLs. Methods: Volunteers were exposed to a psychological stressor (N=24). Flow cytometry identified CD8TL subsets by CCR7, CD27, CD28 and CD45RA expression. Adrenergic receptor subtype expression was determined by micro-array. The effects of βPAR stimulation on IFN-γ production in activated CD8TLs was tested in vitro using PMA/Ionomycin. Results: Stress caused selective migration of effector-memory (CCR7−CD27−CD28−) CD8TLs into the blood (+148%, p<.001). An 8-fold up-regulation of the β2AR was demonstrated in effector-memory cells as compared to naïve CD8TLs. Stimulation of the β2AR subtype completely inhibited IFN-γ production. Conclusion: These results show that β2AR stimulation enhances peripheral immune surveillance in a highly selective manner, and might protect against excessive cytokine release during inflammation and stress.
Copper oxide nanoparticles (CuO NPs) are used as a biocide in paints, textiles and plastics. Their application may lead to the contamination of aquatic ecosystems, where potential environmental effects remain to be determined. Toxic effects may be related to interactions of NPs with cellular systems or to particles' solubilisation releasing metal ions. In this report, we evaluated CuO NPs and soluble copper effects on photosynthesis of the aquatic macrophyte Lemna gibba L to determine the role of particle solubility in NPs toxicity. When L. gibba plants were exposed 48 h to CuO NPs or soluble copper, inhibition of photosynthetic activity was found, indicated by the inactivation of Photosystem II reaction centers, a decrease in electron transport and an increase of thermal energy dissipation. Toxicity of CuO NPs was mainly driven by copper ions released from particles. However, the bioaccumulation of CuO NPs in plant was shown, indicating the need to evaluate organisms of higher trophic level. 相似文献
Purpose Functional capacity evaluations (FCE) are used to identify work abilities and are commonly integrated into rehabilitation programs. We studied whether integrating FCE into rehabilitation leads to better outcomes for injured workers. Methods A cluster randomised controlled trial was conducted at a workers’ compensation rehabilitation facility (registration ISRCTN61284905). Clinicians were randomised into 2 groups: 1 group used FCE while another conducted semi-structured functional interviews. Outcomes included recommendations following assessment, rehabilitation program outcomes including functional work levels and pain intensity, as well as compensation outcomes at 1, 3, and 6 months after assessment. Analysis included Mann–Whitney U, Chi square and t tests. Results Subjects included 225 claimants of whom 105 were tested with FCE. Subjects were predominantly employed (84 %) males (63 %) with sub-acute musculoskeletal conditions (median duration 67 days). Claimants undergoing FCE had ~15 % higher average functional work levels recommended at time of assessment (Mann–Whitney U = 4,391.0, p < 0.001) but differences at other follow-up times were smaller (0–8 %), in favour of functional interviewing, and not statistically significant. Clinically important improvement during rehabilitation in functional work level (0.9/4, SRM = 0.94), pain intensity (2.0/10, SRM = 0.88) and self-reported disability (21.8/100, SRM = 1.45) were only observed in those undergoing the functional interview. Conclusions Performance-based FCE integrated into occupational rehabilitation appears to lead to higher baseline functional work levels compared to a semi-structured functional interview, but not improved RTW rates or functional work levels at follow-up. Functional interviewing has potential for efficiency gains and higher likelihood of clinically important improvement following rehabilitation, however further research is needed. 相似文献