Breakthrough pain with the fentanyl patch.
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Biomedical subjects
Publications and source records attributed to M McCaffery.
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Previous attempts to immunize melanoma patients against GD3 ganglioside have been unsuccessful because of the poor immunogenicity of GD3. BEC2, an anti-idiotypic monoclonal antibody that mimics GD3, can induce anti-GD3 IgG in rabbits. Since clinical trials with BEC2 in melanoma patients demonstrated that BEC2 alone is not highly immunogenic, we have carried out sequential clinical trials exploring the use of two immunological adjuvants, BCG and QS21, administered with BEC2. Melanoma patients free of disease after surgical resection but at high risk for recurrence were immunized either with BEC2/BCG (14 patients) or BEC2/QS21 (6 patients). All patients developed high-titer IgG antibodies against BEC2, demonstrating that both adjuvants effectively enhanced the immunogenicity of BEC2. Anti-GD3 antibodies were induced in 3 of 14 patients immunized with BEC2/BCG; no patient immunized with BEC2/QS21 developed detectable anti-GD3 antibodies. After a median follow-up of 2.4 years, 71% of the patients immunized with BEC2/BCG remain alive and 64% are free of disease. In patients immunized with BEC2/BCG, no apparent association was observed between class II HLA type and either development of anti-GD3 antibodies or survival. We are encouraged by the results with BEC2/BCG, which suggest that further enhancement of the immune response to BEC2 will result in more frequent anti-GD3 antibody responses among immunized patients.
Surveys of nurses' knowledge of cancer pain management were conducted in five countries: Australia, Canada, Japan, Spain, and the United States. The results reveal that, in all countries, serious knowledge deficits exist that could adversely affect the care of patients with cancer pain. It appears, however, that the longer a country has been engaged in efforts to educate health-care professionals and the public and to establish palliative care programs, the more likely are nurses from that country to possess correct information about cancer pain. Nevertheless, survey results in all countries strongly suggested the need to continue aggressive measures to educate nurses, who are the cornerstone of palliative care.
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The SecA protein is an essential, azide-sensitive component of the bacterial protein translocation machinery. A SecA protein homolog (CPSecA) now identified in pea chloroplasts was purified to homogeneity. CPSecA supported protein transport into thylakoids, the chloroplast internal membrane network, in an azide-sensitive fashion. Only one of three pathways for protein transport into thylakoids uses the CPSecA mechanism. The use of a bacteria-homologous mechanism in intrachloroplast protein transport provides evidence for conservative sorting of proteins within chloroplasts.
Nuclear encoded thylakoid lumen proteins are imported into the chloroplast storma and further directed across thylakoid membranes by lumen targeting domains. Recently, we showed that there are two protein-specific pathways for transport into the lumen. This was unexpected in that lumen targeting domains have similar properties, all containing bacterial signal peptide motifs. Nevertheless, sequence homology analysis suggests that pathway specificity is determined by elements in the lumen targeting domain. To test this, we constructed and analyzed chimeric proteins in which transit peptides from proteins transported by one pathway were fused to the mature domains of proteins directed by the other. We also investigated the transport characteristics of a previously unexamined protein whose pathway was predicted by sequence similarity analysis. Our results confirm that lumen targeting domains contain pathway sorting elements and further indicate that distinct energy and stroma requirements for transport are pathway characteristics, unrelated to the passenger protein. These findings suggest the operation of two mechanistically different translocators.
The citrus tristeza closterovirus (CTV) RNA genome was cloned as cDNA generated from both CTV-specific double-stranded RNA and genomic RNA, and the sequence of the 3' 7292 nucleotides was determined. The sequenced portion contained eight open reading frames potentially encoding, in the 5' to 3' direction, proteins with the apparent molecular weights of 65, 61, 27, 25 (capsid protein, CP), 18, 13, 20, and 23 kDa, and a potential noncoding region of 277 nucleotides. The 65-kDa protein is a viral homolog of cellular hsp70 heat shock proteins (hsp), the 61-kDa protein is distantly related to the hsp90 proteins, and the 27-kDa protein is a diverged copy of the CP. Database searches did not identify any protein sequences of significant similarity to the remaining four ORFs downstream of the CP. A specific four-gene module consisting of the hsp70 protein, the hsp90-related protein, the diverged copy of the CP, and the CP itself was found to be common in organization between CTV and beet yellows closterovirus. All four proteins in this module were highly conserved, indicating that these viruses probably have evolved from a common ancestor.
This article reports the results of a survey of 204 persons with chronic nonmalignant pain who were members of a national self-help organization. The survey evaluated the organization, explored the perceived effect of pain on quality of life, and assessed experiences with and perceptions of health-care providers. Response rate was 40%. Of survey respondents, 50% reported inadequate pain relief. Respondents identified depression as one of the worst problems caused by their chronic pain: 50% reported that they had considered suicide due to feelings of hopelessness associated with their pain, 51% reported taking only as much medication as prescribed, and 44% reported taking less medication than prescribed. Further investigation is needed to describe the personal impact of chronic nonmalignant pain.