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Paediatric palliative care and neurodisability are two relatively new, evolving paediatric sub-specialities that have increasing relevance in the current paediatric landscape. For many people palliative care has been synonymous with end of life care, but in paediatrics it encompasses much more and is for all children with life-threatening or life-limiting conditions, from the point of diagnosis. This breadth of focus is demonstrated well through the interface between paediatric palliative care and paediatric neurodisability. In this article we explore this unique interface through the three domains of complex symptom management, advanced care planning and end of life care. We describe the practicalities involved in all three areas and highlight the importance of early referral and the process of “dual” or “parallel” planning. We cover in more depth the specific management of the symptoms: dystonia/abnormalities of muscle tone, seizures, pain, agitation, secretions, respiratory failure, and gut failure. 相似文献
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Matt Farrer Fabienne Wavrant-De Vrieze Richard Crook Lizzie Boles Jordi Perez-Tur John Hardy William G. Johnson John Steele Demetrius Maraganore Katrina Gwinn Tim Lynch 《Annals of neurology》1998,43(3):394-397
A mutation in exon 4 of the α-synuclein (NACP) gene has been reported to explain the chromosome 4 linkage to autosomal dominant Parkinson's disease. We developed primers and methods for exonic sequencing of this gene and sequenced the entire coding region of the gene in 6 families with autosomal dominant disease and in 2 cases of lytico and bodig from Guam. In addition, we have sequenced exon 4 of this gene in 5 cases of familial disease and have screened for the specific mutation (A53T) in a 40 cases of idiopathic Parkinson's disease, 3 cases of multisystem atrophy, and 15 cases of Lewy body dementia. We have found no genetic variation in the gene. We discuss these findings with respect to both the epidemiology of Parkinson's disease and the possibility that NACP is not the chromosome 4 locus for disease. 相似文献
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Induction of unresponsiveness limits tumor protection by adoptively transferred MDM2-specific cytotoxic T lymphocytes 总被引:2,自引:0,他引:2
Bendle GM Holler A Pang LK Hsu S Krampera M Simpson E Stauss HJ 《Cancer research》2004,64(21):8052-8056
There is evidence showing that high avidity CTLs can be more effective than low avidity CTLs for adoptive tumor immunotherapy. Because many T cell-recognized tumor antigens are nonmutated self-proteins, tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We recently used the allo-restricted strategy to circumvent immunologic tolerance to a ubiquitously expressed tumor-associated protein, MDM2, and raised high avidity CTLs in humans and in mice. In this study, we investigated whether high avidity MDM2-specific CTLs can mediate tumor protection without causing damage to normal tissues in mice. Although the CTLs prolonged survival of tumor-bearing mice without causing damage to normal tissues, tumor protection was incomplete. We show that tumor growth occurred despite the continued presence of MDM2-specific CTLs and the continued susceptibility of tumor cells to CTL killing. However, analysis of the CTLs revealed that they had been rendered unresponsive in vivo because they did not produce interferon gamma in response to antigen-specific stimulation. These experiments suggest that induction of unresponsiveness may be an important mechanism limiting the efficacy of adoptive CTL therapy. 相似文献
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Bendle JS James PA Bennett PM Avison MB Macgowan AP Al-Shafi KM 《International journal of antimicrobial agents》2004,24(6):619-621
Ninety-three clinical isolates of Clostridium difficile, comprising 65 from Royal Gwent Hospital, Newport and 28 from Southmead Hospital, Bristol were examined to determine the prevalence of genes coding for macrolide resistance and to explore differences in susceptibility patterns. Antibiogram testing produced similar results for both sets of strains with respect to amoxicillin, tetracycline, erythromycin and cefotaxime. Results differed for rifampicin, where 53% of the Bristol isolates were resistant, compared with 3% of the Newport isolates. Clindamycin disc susceptibility testing produced similar resistance rates. However, clindamycin MIC determinations revealed that 53% of the Bristol strains exhibited high-level resistance (MIC > 256 mg/L), whereas strains from Newport had clindamycin MICs ranging from 0.25 to 3 mg/L. erm (B) was present in 15 of the strains from Bristol and in none of the Newport strains. erm (F) and erm (Q) were not detected in either population. The two geographically distinct populations of C. difficile differed considerably in their susceptibility to antibiotics. The possibility that C. difficile may serve as a conservator for resistant determinants subsequent to exposure to antimicrobial agents, has important implications for infection control. 相似文献