Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints.
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PMID:Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester. 1077 54

Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints.
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PMID:Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester. 1044 Sep 96

This work was undertaken by the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) as a demonstration project in developing clinical guidelines relevant to palliative care from a pragmatic approach to literature review and grading of clinical evidence. CANCERLIT and Embase were searched for relevant papers written in English, published since 1980. Each study identified was rated against agreed criteria for levels of evidence. Most studies were not specifically designed to define speed of response, and were not undertaken in palliative care patients. Thus, careful reading and grading of each study was necessary. Sufficient evidence was identified to make recommendations for clinical practice in a palliative care population of patients, and areas for future research have been identified. Bisphosphonates appear to have a role in managing pain from metastases which has been refractory to conventional analgesic management and where oncological or orthopaedic intervention is delayed or inappropriate.
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PMID:Using bisphosphonates to control the pain of bone metastases: evidence-based guidelines for palliative care. 1121 75

Unintentional dural puncture is the most frequent cause of postdural puncture headache (PDPH) in epidural anesthesia and analgesia. Conservative treatments of PDPH include bed rest, oral analgesics, and hydration. When conservative measures fail, epidural blood patch is an effective substitute. However, epidural blood patch carries some risks, such as subdural hematoma, pneumocephalus, exacerbation of PDPH and new dural puncture. Many patients may refuse the procedure due to the risks involved. We describe a female patient who had her PDPH successfully treated with epidural saline delivered by a patient-controlled analgesia device (Abbott Pain Management-APM) without molestation of her daily activities.
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PMID:Management of postdural puncture headache by epidural saline delivered with a patient-controlled pump--a case report. 1723 68

A task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) was convened to produce some up-to-date, evidence-based, practical, clinical guidelines on the management of cancer-related breakthrough pain in adults. On the basis of a review of the literature, the task group was unable to make recommendations about any individual interventions, but was able to make a series of 12 recommendations about certain generic strategies. However, most of the aforementioned recommendations are based on limited evidence (i.e., case series, expert opinion). The task group also proposed a definition of breakthrough pain, and some diagnostic criteria for breakthrough pain.
Eur J Pain 2009 Apr
PMID:The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. 1921 83