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)

Peripheral arterial disease of the lower limbs is a manifestation of atherosclerosis, and may also affect other vascular territories such as the coronary and cerebral arteries. Progressive narrowing of the vessels up to total occlusion can present as intermittent claudication or pain at rest, with or without cutaneous lesions. Patients with intermittent claudication are at a low risk of amputation, and the symptom has to be regarded as a warning signal for myocardial infarction and stroke. Nevertheless, if the patient's walking distance is too limited to allow a near-normal life, symptomatic treatment to improve quality of life should be considered. Treatment may consist of walking exercise, surgical or interventional radiological revascularisation, or, in some cases, administration of vasoactive drugs. Antiplatelet agents should be administered in an attempt to limit disease progression and prevent cardiac and cerebrovascular complications, together with active measures to reduce established risk factors such as smoking, diabetes, hyperlipidaemia, and arterial hypertension. The presence of pain at rest indicates that a lower limb is jeopardised, especially when the criteria for critical ischaemia have also been met. These criteria include the presence of chronic (lasting for more than 2 weeks) symptoms of ischaemia at rest and a systolic blood pressure less than 50 mm Hg or 30 mm Hg at the ankle or big toe, respectively. In such a situation, revascularisation should be attempted whenever possible. If this is not possible or if the procedure has failed, prostacyclin administered intravenously for days or weeks is an alternative. After revascularisation, early reocclusion may be prevented by administering anticoagulants and late reocclusion by antiplatelet agents, in conjunction with eradication of risk factors. In all situations, therapeutic decision-making should be undertaken in a multidisciplinary setting and should include the following: specialists in angiology (an internist) and interventional radiology; a vascular surgeon; an orthopaedic surgeon, if necessary; and diabetes and infectious disease specialists.
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PMID:[Drug treatment strategies for peripheral obliterative arteriopathy]. 984 99

To help in determining management strategy as an alternative to amputation by using a synthetic prostacycline, a preliminary study was undertaken in 12 patients (11 men and one woman), with a mean age of 71.08 years, ie, 13 limbs evaluated at the stage of amputation. All patients were treated with a combination of iloprost and physical therapy (massage, specific exercises, cardiorespiratory training). Static transcutaneous oxygen pressure (TcPO2) was measured, with a sensitization test by verticalization and inhalation of oxygen, on day (D) D0, D15, D28, D60, D180, and D365. Results were analyzed in absolute terms and by tissue oxygenation ratio (TOR) (ratio between absolute values of TcPO2 in the foot and those of a reference chest electrode). Supine TOR and vertical TOR, with values of 36.67 and 65.08, respectively, appeared to be significantly linked to the variable "preservation of limb". At 1 year, seven limbs were preserved (53.85%) while amputation had been scheduled for all the patients treated. Evidence was found in all patients who kept their limb of stability (7.69%) and a decrease in (30.77%) or disappearance of pain (15.38%) at 1 year.
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PMID:Prognostic aspects of TcPO2 in iloprost treatment as an alternative to amputation. 1022 63

Acute cholecystitis is associated with increased gallbladder prostanoid formation and the inflammatory changes and prostanoid increases can be inhibited by nonsteroidal anti-inflammatory agents. Recent information indicates that prostanoids are produced by two cyclooxygenase (COX) enzymes, COX-1 and COX-2. The purpose of this study was to determine the COX enzymatic pathway in gallbladder mucosal cells involved in the production of prostanoids stimulated by inflammatory agents. Human gallbladder mucosal cells were isolated from cholecystectomy specimens and maintained in cell culture and studied in comparison with cells from a well differentiated gallbladder mucosal carcinoma cell line. COX enzymes were evaluated by Western immunoblotting and prostanoids were measured by ELISA. Unstimulated and stimulated cells were exposed to specific COX-1 and COX-2 inhibitors. In both normal and transformed cells constitutive COX-1 was evident and in gallbladder cancer cells lysophosphatidyl choline (LPC) induced the formation of constitutive COX-1 enzyme. While not detected in unstimulated normal mucosal cells and cancer cells, COX-2 protein was induced by both lipopolysaccharide (LPS) and LPC. Unstimulated gallbladder mucosal cells and cancer cells produced prostaglandin E2 (PGE2) and prostacyclin (6-keto prostaglandin F1alpha, 6-keto PGF1alpha) continuously. In freshly isolated normal gallbladder mucosal cells, continuously produced 6 keto PGF1alpha was inhibited by both COX-1 and COX-2 inhibitors while PGE2 levels were not affected. Both LPS and LPC stimulated PGE2 and 6 keto PGF1alpha formation were blocked by COX-2 inhibitors in freshly isolated, normal human gallbladder mucosal cells and in the gallbladder cancer cells. The prostanoid response of gallbladder cells stimulated by proinflammatory agents is inhibited by COX-2 inhibitors suggesting that these agents may be effective in treating the pain and inflammation of gallbladder disease.
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PMID:Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2. 1032 26

A retrospective review of all patients presenting to a tertiary referral center with acute nontraumatic upper limb ischemia between January 1992 and June 1997 was undertaken to examine the role of intraarterial thrombolysis in the management of such cases. Twenty-one patients were identified in the radiology and vascular surgery departments' registers. Twenty (95%) underwent angiography, demonstrating subclavian artery occlusion in four, axillary in two, brachial in 13, and one at the digital level. Intraarterial thrombolysis was attempted in 12 patients. There were three technical failures, all requiring embolectomy. Six had complete lysis and resolution of their symptoms. One patient had partial lysis but experienced no further rest pain. Thrombolysis was unsuccessful in two cases with one subsequently requiring embolectomy and the other surgical bypass. Three patients had surgical intervention as their primary procedure with two favorable outcomes and one ending in above-elbow amputation. Five patients were treated conservatively with heparin, resulting in three partial and two full recoveries. One patient experienced complete resolution of symptoms with an intravenous prostacyclin infusion. Both electrocardiograms (ECG) and echocardiograms (ECHO) were of limited diagnostic aid, and long-term warfarin anticoagulation was prescribed to all patients. There was no recurrence of upper limb ischemia at a median follow up of 18 months. Intraarterial thrombolysis is an effective first line treatment for acute nontraumatic upper limb ischemia in selected cases.
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PMID:Management of acute nontraumatic upper limb ischemia. 1049 97

The aim of this retrospective, study was to assess the tolerance and therapeutic effect of a stable prostacyclin (iloprost) analog in severe forms of permanent lower limb ischemia. Ninety consecutive unselected patients, in Leriche and Fontaine stages III or IV, turned down for vascular surgery after angiography and treated with iloprost for 28 days were enrolled in the study. Patients were followed up clinically (ischemic pain, trophic changes, walking distance) and with transcutaneous oxymetry (D28). Long-term assessment (mean 2 years) was expressed as rates of death, major amputation and "patients alive with limb". There were no manifestations of intolerance to iloprost. At two months, 42 out of 90 patients (47%) were considered as responders because of a lack (n=36) or significant decrease (n=6) in pain, reduction of trophic lesions and conservative walking. At long term (6 months, one and two years) we observed that 10 (11%), 17 (20%) and 22 (25%) patients respectively had died, 24 (27%), 26 (30%) and 28 (32%) patients underwent major amputation, but 60 (68%), 54 (62%) and 49 (56%) patients still alive with their limb and conservative walking. No predictive factors were noted, but diabetic patients without microangiopathy or recent bypass occlusions (respectively 43% and 56% out of patients were alive with limb at 6 months) were associated with bad results. This retrospective study, despite its limitations, underlines the good tolerance to, and effectiveness of iloprost in non surgical chronic critical ischemia. However, no predictive criterion of long-term effectiveness could be established, except initial clinical severity and clinical change one month after treatment.
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PMID:[Tolerance and therapeutic results of iloprost in obliterative arteriopathy in lower limbs at the severe chronic ischemia stage. A retrospective study of 29 consecutive cases]. 1070 32

Inflammatory signs, such as heat, redness, swelling and pain, have been described from the Greek era. In these phenomena various endogenous active substances, i.e., inflammatory mediators, could cause and manifest vascular dilatation, a vascular permeability increase and sensitization of pain receptors, etc. In order to evaluate the roles of inflammatory mediators, we have studied the time courses of inflammatory reaction along with detection of various active substances directly or indirectly in the experimental animal model of pleurisy, such as rat carrageenin-induced, and zymosan-induced pleurisy. These pleurisies showed almost similar time courses of pleural exudate accumulation and neutrophil migration. However, mediators detected in the exudates of such pleurisies were different; in carrageenin-induced pleurisy bradykinin and prostacyclin (PGI2) caused exudate formation, while zymosan-induced pleurisy showed early degradation of mast cells and activation of complements, followed by an increase in platelet activating factor (PAF). In both pleurisies TNF alpha, IL-1, IL-6 and CINC (cytokine-induced neutrophil chemoattractant) appeared similarly in the exudates to cause chemoattractant for neutrophils. TNF alpha and IL-1 could stimulate to produce IL-6 and IL-8. While prostaglandins may regulate cytokine production via a cellular cAMP-dependent mechanism. Thus one should consider the time for application of anti-inflammatory drugs, such as cyclooxygenase inhibitor, indomethacin, since it causes increases in TNF alpha and IL-1 production by reducing PGI2 and prostaglandin E2 (PGE2) levels. In conclusion, inflammatory reaction has its own automatic regulation mechanism through complex cross talks between inflammatory mediators.
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PMID:[Evaluation of time course and inter-relationship of inflammatory mediators in experimental inflammatory reaction]. 1082 9

(1) Iloprost, a vasodilatory prostacyclin analogue administered by infusion, is indicated for second-line therapy in patients with severe ischaemia of the lower limbs, when surgical revascularisation fails or is contraindicated. (2) In thromboangiitis obliterans the clinical file on iloprost has remained inadequate since the product was first released. (3) A meta-analysis of 6 clinical trials giving conflicting results in patients with stage III or IV lower-limb arterial disease favoured iloprost. But the results of this meta-analysis are uninterpretable because of methodological biases. It is not known what effects iloprost has in the short term (on pain and skin damage) or in the long term (on the risk of amputation). (4) The iloprost dose must be adjusted individually according to adverse effects linked to vasodilation.
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PMID:Iloprost: new indication. Not adequately assessed. 1084 61

Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal anti-inflammatory drugs, specific COX-2 inhibitors do not inhibit platelet activation. However, these agents significantly reduce systemic production of prostacyclin. As a result, theoretical concerns have been raised that specific COX-2 inhibitors could shift the hemostatic balance toward a prothrombotic state. Patients with connective tissue diseases (CTD), who may be predisposed to vasculopathy and thrombosis, often have arthritis or pain syndromes requiring treatment with antiinflammatory agents. Herein we describe 4 patients with CTD who developed ischemic complications after receiving celecoxib. All patients had a history of Raynaud's phenomenon, as well as elevated anticardiolipin antibodies, lupus anticoagulant, or a history compatible with antiphospholipid syndrome. It was possible to measure a urinary metabolite of thromboxane A2 in 2 of the patients as an indicator of in vivo platelet activation, and this was markedly elevated in both. In addition, the patients had evidence of ongoing inflammation as indicated by elevated erythrocyte sedimentation rate, hypocomplementemia, and/or elevated levels of anti-DNA antibodies. The findings in these 4 patients suggest that COX-2 inhibitor-treated patients with diseases that predispose to thrombosis should be monitored carefully for this complication.
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PMID:Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors. A report of four cases. 1135 60

Currently available drug therapies for patients suffering severe ischaemia with rest pain and trophic lesions of the limbs remain unsatisfactory. Also vascular reopening procedures are suitable in only about half of the patients. In atherosclerotic disease when the vascular endothelium is damaged prostacyclin synthesis is decreased and thromboxane A2 production increases. Prompted by this knowledge of the importance of prostacyclin in pathogenesis of atherosclerotic disease an attempt was made to employ PGI2 clinically--for treatment of advanced forms of peripheral arterial atherosclerotic disease. Favourable effects of the stable analogue of prostacyclin (Iloprost), were reported in various studies, which included patients with peripheral atherosclerotic arterial disease, thromboangiitis obliterans and Raynaud's phenomenon. The use of Iloprost resulted in a significantly superior response than other drugs and placebo in terms of alleviation of rest pain, ulcer healing and decrease of amputation rate of ischaemic limbs. Therefore prostacyclin provides a therapeutic option in patients with advanced forms of arterial disease--including critical ischaemia.
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PMID:Possibilities for clinical use of prostacyclin in vascular disease. 1100 43

Inhibition of prostaglandin biosynthesis via inhibition of the fatty acid cyclooxygenase (COX) is the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). This results in an inhibition of the inflammatory and pain-producing activities of prostaglandins at a site of tissue injury but also in inhibition of prostaglandin production in the gastrointestinal tract (GI) and platelets, i.e. sites where endogenous prostaglandins are possibly involved in control of physiological functions. The discovery of two COX isoenzymes, COX-1 and COX-2, and the detection of their separate function and regulation, has initiated the search for new and putatively more selective inhibitors of prostaglandin biosynthesis. Specifically, selective inhibitors of COX-2 were developed in order to improve the anti-inflammatory and analgetic specificity and potency of the compounds and to reduce side-effects in the GI tract. Available experimental and clinical data of selective COX-2 inhibitors, including flosulide, celecoxib or rofecoxib, suggest improved gastric tolerance as compared to conventional, non-selective NSAIDs. However, experimental evidence suggests that both, the analgetic and anti-inflammatory action of COX-inhibitors, might also require inhibition of COX-1. COX-2-selective compounds at anti-inflammatory doses might have other side-effects, and for example reduce vascular prostacyclin production. Evidence is accumulating that COX-2 might not only be considered as a putatively detrimental enzyme but rather a highly regulated enzyme that also contributes to tissue protection and is even constitutively expressed in healthy human stomach mucosa. This paper reviews some of these newer aspects of COX-2-selective inhibitors in clinical use and discusses their possible benefits and risks.
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PMID:Cyclooxygenase-2 inhibition and side-effects of non-steroidal anti-inflammatory drugs in the gastrointestinal tract. 1103 62


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