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)

Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.
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PMID:Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease. 770 72

Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients (23%) had progressive disease (PD). The median survival time was 10 months for all patients, 22 months for patients with partial remission and 5 months for patients with progressive disease. Many patients with tumour-related pain whose tumours were affected in terms of PR, MR, NC were free of pain during treatment with this regimen (22/36 patients). The common toxicities observed were fever (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical modulation of 5-FU with FA and IFN-alpha has some positive effects in the treatment of pancreatic cancer of moderate toxicity.
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PMID:Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial. 781 23

Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy. The protocol was generally well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment-related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN-alpha 2b in refractory myeloma.
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PMID:Recombinant interferon-alpha 2b and high dose methyl prednisolone in relapsed and resistant multiple myeloma. 814 32

The efficacy of r-interferon alpha 2a (IFM) versus acyclovir (ACV) and vitamin therapy in the treatment of herpes zoster is reported. A total of 305 patients were randomly divided into 3 groups. One million units of IFN were administered i.n. once a day for 6 days in 223 cases, oral ACV 200 mg five times daily for 7 days in 34 cases, and vitamin B12, B1 and B2 therapy at conventional doses for 7-14 days in 48 cases. The results showed that both IFN and ACV could reduce pain in patients with herpes zoster and cut the total duration of symptoms, in comparison with vitamin therapy (P < 0.01). In the IFN group, 45 patients (20.2%) experienced side effects, including mild fever in 35 cases (15.7%) and a slightly depressed leukocyte count or increased serum ALT level (3 cases each). In the ACV group, one complained of discomfort in the gastroenteric tract, and another patient reported lumbodynia.
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PMID:Treatment of herpes zoster: recombinant alpha-2a-interferon versus acyclovir and vitamin therapy. Clinical Study Group on Interferon. 827 20

This investigation is devoted to the study of the time-course of a cytokines panel (IL-4, IL-6, IFN-gamma, GM-CSF) in plasma samples from migraine patients. The data obtained during challenged migraine crises was compared to the baseline values. Time-data series analysis showed a fall after a challenge test for IL-4 and IL-6 plasma levels and an opposite trend for gamma-IFN and GM-CSF levels. The implication of this phenomenon in dietary migraine is not readily evident. There may possibly be an activation of this cytokine network together with the well-known impairment in the neuropeptidergic system, considering the close links between interleukins and other cytokines and the neuro-mediators of pain, such as histamine and 5-HT.
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PMID:Disruption of the immunopeptidergic network in dietary migraine. 829 90

A Case of drug-induced immune hemolytic anemia during alpha-interferon (alpha-IFN) therapy for renal cell carcinoma is reported. A 61-year-old woman was admitted to Tochigi cancer center for the treatment of left renal cell carcinoma. She underwent left radical nephrectomy. From 7th post operative day, alpha-IFN (6 x 10(6) IU) was administered every other day. Diclofenac and indomethacin were administered for pain and high fever induced by alpha-IFN. Hemoglobinuria was first noted on 20th post operative day. Immune hemolytic anemia was suspected by blood examinations including Coombs' test, serum haptoglobin, serum LDH and serum GOT. alpha-IFN therapy and administration of diclofenac and indomethacin were discontinued and prednisolone therapy (50 mg daily) was begun. Hemoglobinuria disappeared by 5 days and laboratory data became in normal range by 3 weeks. Drug-induced immune hemolytic anemia was diagnosed by the process of laboratory data, especially of direct Coombs' test. Though drug-induced immune hemolytic anemia is a rare adverse side effect during alpha-INF therapy for renal cell carcinoma, it seemed an important complication.
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PMID:[A case of drug-induced immune hemolytic anemia during alpha-interferon therapy for renal cell carcinoma]. 870 50

Patients with advanced adenocarcinomas of the pancreas have an exceptionally poor prognosis. Modest activity has been demonstrated with single agents (response rates of 25% at best with 5-fluorouracil [5-FU] and mitomycin). Better results have not been obtained by combination chemotherapy. Improvements in the palliation have been achieved by treatment with 5-FU, folinic acid (FA), and interferon-alpha-2A (IFN-alpha) weekly in the context of a phase II trial. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR), and 28 (49%) had no change of disease (NC). The median survival time was 10 mo for patients with progressive disease. Twenty-two out of 36 patients with tumor-related pain whose tumors were affected in terms of PR, MR, and NC became free of pain during treatment. Fever (56%), nausea (37%), and diarrhea (33%) were common toxicities observed. Therefore, biochemical modulation of 5-FU with FA and IFN-alpha shows some positive effects in the treatment of pancreatic cancer with moderate toxicity.
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PMID:Chemotherapy in advanced pancreatic cancer. 912 72

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76

A 59-year-old man with chronic myelogenous leukemia (CML) had a white-blood-cell (WBC) count of 55,400/microliter when admitted in July 1997, and was placed on oral hydroxyurea (HU) of 1,500 mg/day. Treatment with 600 MU/day of interferon alpha (IFN alpha) was started on August 5. HU was discontinued when the patient's WBC count dropped to 8,100/microliter on August 18. However, HU was resumed about a month later, after his WBC count increased to 10,100/microliter, but discontinued when the patient started to complain of chills, high fever, and bilateral femoral pain. HU treatment was initiated again one week later, after the patient's WBC count had begun rising but ceased again after he experienced chills, high fever, and bilateral femoral pain. The patient's myogenetic enzymes were found to be increasing the following day, and a lymphocyte stimulation test (LST) with HU showed a high stimulation index of 41.7%. The elevation of myogenetic enzymes and the results of the LST suggested that myositis due to HU was the cause of the patient's clinical manifestations. His myositis spontaneously disappeared after HU was discontinued. Although the patient is no longer receiving HU, IFN alpha has brought his CML under control. To our knowledge, this is the first reported case of myositis caused by HU.
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PMID:[Myositis caused by hydroxyurea in a patient with chronic myelogenous leukemia]. 979 2

Intralesional therapy is a less invasive method for the treatment of Peyronie's disease. The objective of this study was to evaluate intralesional injections of interferon alpha 2B (IFN-alpha-2B) as an effective alternative to the surgical treatment of Peyronie's disease. Twenty-one patients with Peyronie's disease were evaluated by use of penile duplex Doppler ultrasonography for cavernosal blood flows, degree of penile curvature, and plaque size. A questionnaire was given to all patients to assess sexual function. Each patient then received biweekly intralesional injections of 1 x 10(6) units of IFN-alpha-2B in 10 ml of normal saline over a period of 6 months. There was no placebo control group in this study. At the conclusion of the study, penile duplex Doppler imaging was repeated. A questionnaire was completed by all patients to assess changes in sexual function after treatment. Twenty patients completed the study, with all men reporting subjective softening of their plaques. Nine of 10 patients initially reporting penile pain with erection (90%) had resolution of their phallalgia while on study protocol. Thirteen patients (65%) had significant improvement in curvature, ranging from 20 to 90%. Seventeen patients (85%) demonstrated an objective 10 to 80% decrease in plaque size. Biweekly intralesional injections of Peyronie's plaques with IFN-alpha-2B resulted in a significant improvement in penile curvature, diminished pain, and reduced plaque size, and resulted in a subjective improvement in sexual function.
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PMID:A pilot study demonstrating clinical benefit from intralesional interferon alpha 2B in the treatment of Peyronie's disease. 1045 84


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