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PubMed1991

[Effect of aspirin on FMLP (formyl-meth-leu-phe)-stimulated leukocytes in patients with asthma and hypersensitivity to aspirin].

In order to determine if aspirin sensitivity effects leukocyte reaction in aspirin sensitive asthma patients the authors studied the influence of aspirin on chemiluminescence in 12 aspirin sensitive asthmatics and 13 non-aspirin asthmatics. Leukocyte suspension were carried out according to Böyum. Chemiluminescence was determined using the LKB--Wallac counter. No statistical differences in leukocyte chemiluminescence was found in both groups.

Adult↗
PubMed1985

Amplification of primary response of human platelets to platelet-activating factor: aspirin-sensitive and aspirin-insensitive pathways.

The irreversible human platelet aggregation induced by threshold concentrations of platelet-activating factor (PAF) in citrated plasma was reversed by aspirin (100 mumol/L, with 10 minutes' preincubation). The aspirin-sensitive amplification was linked to thromboxane generation, although thromboxane could be successfully replaced by cyclic endoperoxides, as suggested by the lack of effect of dazoxiben, a selective thromboxane-synthase inhibitor. The inhibitory effect of aspirin could be overcome by using 10 times higher PAF concentrations or, even more effectively, by combining threshold concentrations of both PAF and one of the other agonists studied (ADP, epinephrine, and U-46619, a stable endoperoxide analog, but not serotonin). The irreversible response obtained in both experimental conditions could also be made reversible by the use of BW 755C or nordihydroguaiaretic acid, inhibitors of both cyclooxygenase and lipoxygenase. It is concluded that the aspirin-sensitive pathway is sufficient but not necessary to amplify the primary response of human platelets to PAF. These data may be relevant to the current debate on the efficacy of aspirin in thrombosis prevention.

Arachidonate Lipoxygenases↗
PubMed1986

A comparison of enteric-coated aspirin granules with plain and buffered aspirin: a report of two studies.

Reported herein are two endoscopic studies performed to compare the gastrointestinal mucosal effects of encapsulated enteric-coated aspirin granules with several other well-known aspirin products. The first study compared the effects of Ascriptin A/D, Bayer, Bufferin, and 325 mg enteric-coated aspirin granules (325 mg Ecotrin capsules); the second study compared Anacin Arthritis Pain Formula, Arthritis Strength Bufferin, Ascriptin A/D, Bayer, and 500 mg enteric-coated aspirin granules (500 mg Ecotrin capsule). In both of these studies the Ecotrin capsule induced less stomach damage than did any of the other aspirin products tested. The Ecotrin capsule was also shown to cause less damage to the proximal duodenum than did Bayer.

Adult↗
PubMed1984

[Aspirin and gastroduodenal toxicity. A double-blind endoscopic study of the effects of placebo, aspirin and lysine acetylsalicylate in healthy subjects].

The aim of this double-blind endoscopic study was to compare the effects of placebo (group I, 5 patients), lysine acetylsalicylate (group II, 7 patients) and acetylsalicylic acid (group III, 7 patients) on the gastric and duodenal mucosa in healthy humans. Endoscopy was performed before and one hour after endoscopic instillation of aspirin (500 mg) or placebo in the stomach. Endoscopy was repeated after one week of aspirin-treatment (2 g per day) or placebo. Endoscopic findings were graded from 0 to 6 with regard to the aspect of the lesions (petechiae, erosions, ulcers) and to their number (less than 10; greater than 10). One hour after placebo instillation endoscopic findings were normal in all the patients of group I. Three and 5 patients of groups II and III, respectively, developed gastric lesions but none had duodenal lesions. At day 8 only one subject from group I had gastric petechiae. After one week of aspirin-treatment, 13 out of the 14 subjects of groups II and III developed gastric lesions and 3 in each group had duodenal lesions. The endoscopic score was significantly higher in group III than in group II for the following localisations: fundus, antrum, entire stomach, and stomach + duodenum. However the duodenal score was not significantly different between these 2 groups. It is concluded that, after a one-week treatment in normal patients, standard aspirin produces 2 fold more gastric mucosal damage than does soluble aspirin.

Adult↗
PubMed1984

Decreased sensitivity to tartrazine after aspirin desensitization in an asthmatic patient intolerant to both aspirin and tartrazine.

An aspirin- and tartrazine-sensitive asthmatic patient underwent a desensitization to the adverse effects of aspirin by oral aspirin challenges. After a month of daily aspirin ingestion, the patient's reactivity to tartrazine, tested by oral challenge, was observed to the blunted. This report suggests that desensitization to the adverse effects of aspirin might protect the patient against the adverse effects of tartrazine.

Adult↗
PubMed1982

A double-blind study comparing benoxaprofen, aspirin, and benoxaprofen plus aspirin in patients with rheumatoid arthritis.

Ten patients with rheumatoid arthritis completed a study that consisted of 30-day treatment periods with aspirin, benoxaprofen, and benoxaprofen plus aspirin. There were two-week placebo washouts between each treatment. The patients were evaluated biweekly for 15 variables. Each variable was compared for each period; a pooled index was calculated on three combinations of variables. The benoxaprofen-plus-aspirin combination was significantly better than aspirin and better than benoxaprofen alone. This study indicates that combining nonsteroidal anti-inflammatory drugs which inhibit different sites of the inflammatory response (i.e., benoxaprofen, an inhibitor of the directional migration of monocytes, with aspirin, a potent inhibitor of prostaglandin synthesis) may be advantageous in treating patients with rheumatoid arthritis.

Adult↗
PubMed1993

Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hypertension. Italian study of aspirin in pregnancy.

Meta-analysis of data from several controlled trials has shown that low-dose aspirin reduces the risk of pregnancy-induced hypertension (PIH) and intrauterine growth retardation (IUGR) in women at high risk of these disorders. We have assessed the efficacy of low-dose aspirin in women judged to be at moderate risk. Women were included on prophylactic criteria--age under 18 or over 40 years, mild or moderate chronic hypertension (diastolic pressure between 90 and 110 mm Hg), nephropathy with normal renal function and blood pressure, history of PIH or IUGR, and twin pregnancy--or therapeutic criteria--PIH or early signs of IUGR in current pregnancy. Eligible women were randomly assigned treatment with 50 mg aspirin daily until delivery (583) or no treatment (523); 18 and 46 women, respectively, were lost to follow-up. The groups were well matched for baseline characteristics. We found no differences between the no-treatment and aspirin groups in numbers of spontaneous (5 vs 2) or therapeutic (1 vs 2) abortions, stillbirths (14 vs 13), perinatal mortality (35.7 vs 28.6 per 1000 births), mean birthweight (2858 [SD 729] vs 2874 [795] g), proportion of infants with birthweights below the 10th centile (95 [18.3%] vs 117 [19.0%]), or births before 37 weeks' gestation (184 [35.6%] vs 209 [33.9%]). Nor did the groups differ in the frequency of PIH with or without proteinuria (51 [15.2%] vs 81 [19.3%]). There was no difference in mean birthweight between the treatment groups in separate analyses according to criteria for trial entry and week of gestation at randomisation. Our study gives little support to the notion that low-dose aspirin is beneficial in women at moderate risk of PIH or IUGR.

Adolescent↗
PubMed1977

Aspirin and gastric ulceration: light and electron microscopic observations in a model of aspirin plus stress-induced ulcerogenesis.

The gastric mucosa of rats given aspirin orally and concomitantly exposed to mild (cold) stress conditions has been examined under the electron microscope. In this model of gastric ulceration greater involvement is seen of the parietal and zymogen cells than is evident after aspirin treatment alone (which leads to mucosal erosions but not ulceration per se). Evidence of considerable autolytic and proteolytic activity is seen in aspirin-plus-stress-treated animals developing in ulceration. Little damage was observed in animals exposed to these mild stress conditions. The synergistic interaction between aspirin and stress could have its basis in greater sensitizing of parietal and zymogen cells to damage not seen in aspirin-treated animals.

Animals↗
PubMed2003

Randomised comparison of uterine artery Doppler and aspirin (100 mg) with placebo in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 2).

OBJECTIVE: To assess the effectiveness of a pre-eclampsia prevention strategy based on routine uterine artery Doppler flow velocity waveform examination during the second trimester of pregnancy, followed by a prescription for 100 mg aspirin in the case of abnormal Doppler findings. DESIGN: Multicentre randomised controlled trial. SETTING: Eleven centres in the north of France and one in Belgium. POPULATION: One thousand and eight hundred and fifty-three nulliparous women recruited between 14 and 20 weeks of gestation. METHODS: Randomisation either to undergo a uterine Doppler examination between 22 and 24 week of gestation or to take a placebo. Women with abnormal Doppler waveforms received 100 mg of aspirin daily from Doppler examination through 36 weeks. MAIN OUTCOME MEASURES: Pre-eclampsia was defined as hypertension (> or = 140 and/or 90 mmHg) associated with proteinuria (> or = 0.5 g/L). RESULTS: One thousand two hundred and fifty-three women (67%) were randomised into the systematic Doppler group and 617 (33%) into the placebo group. Of the 1175 patients in the Doppler group who underwent this examination, 239 (20.3%) had abnormal uterine artery Doppler and received a prescription for aspirin. Despite the aspirin prescription, the frequency of pre-eclampsia did not differ between the systematic Doppler group and the placebo group (28 of 1237 [2.3%] vs 9 of 616 [1.5%]; RR = 1.55, 95% CI 0.7-3.3). Furthermore, the groups did not differ in the frequency of children who were very small for their gestational age (< or =3rd centile) or for perinatal deaths. Compared with patients with normal Doppler findings, those with abnormal Doppler were at high risk of pre-eclampsia (RR = 5.5, 95% CI 2.5-12.2) and of giving birth to a small-for-gestational-age child (RR = 3.6, 95% CI 1.6-8.1). CONCLUSION: Despite its sensitivity in screening for pre-eclampsia, routine uterine Doppler in the second trimester cannot be recommended for nulliparous patients.

Adult↗
PubMed2001

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS).

BACKGROUND: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation. OBJECTIVE: Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation. METHODS: A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications. RESULTS: The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003). CONCLUSION: The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.

Administration, Oral↗
PubMed1986

The interaction of noise and aspirin in the chick basilar papilla. Noise and aspirin toxicity.

The possible synergism between noise and aspirin for causing cochlear damage was examined histologically. Six chicks fed aspirin for five days and five chicks fed a normal diet only were paired and placed in sound chambers. They were exposed to a 1500-Hz tone at 115 dB sound pressure level for eight hours. The mean serum salicylate level just before noise exposure was 24 mg/dL (1.74 mmol/L). Ten days later they were killed, and the temporal bones were processed. Hair cell counts were made at 100-microns intervals throughout the length of the basilar papilla (cochlea). The noise produced a discrete cochlear lesion centered about 30% of the distance from the base to apex. The addition of aspirin did not significantly alter the extent or location of this lesion. One aspirin-fed chick had a unilateral middle ear effusion, and a striking shift in the center of damage toward the apex was noted in this cochlea.

Animals↗
PubMed1983

Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole.

Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.

Aspirin↗
PubMedDate not supplied

The role of aspirin-triggered lipoxins in the mechanism of action of aspirin.

Few drugs have treated so many diseases, provided us with so much understanding of their pathogenesis, and tested our scientific creativity over the last 100 years as much as aspirin. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase (COX 2)-derived prostanoids, fatty acid metabolites that modulate host defense and regulate the cardiovascular system. However, the inhibition of COX 2 enzyme activity and prostaglandin synthesis has never fully explained aspirin's repertoire of anti-inflammatory effects, leaving many questions pertaining to its true mechanism of action unanswered. Here, data from a series of comparatively recent experiments exploring aspirin's unique ability to acetylate the active site of inducible COX 2 and generate a family of lipid mediators called the epi-Lipoxins will be discussed in light of their ability to exert profound modulatory effects on the innate and adaptive immune systems.

Animals↗
PubMed2000

A moderate and unspecific release of cysteinyl leukotrienes by aspirin from peripheral blood leucocytes precludes its value for aspirin sensitivity testing in asthma.

Aspirin-induced asthma (AIA) is a clinical syndrome related to cysteinyl leukotriene overproduction in airways. The confirmation of the diagnosis requires inconvenient provocation tests with acetyl salicylic acid (ASA). A study was performed to evaluate whether measurement in vitro of cysteinyl leukotrienes (cys-LTs) release by isolated peripheral blood leucocytes, stimulated with ASA, can be of use for diagnosis of AIA. A cellular allergen stimulation test, CAST, was adapted to measure leukotriene release from leucocytes of 32 aspirin-tolerant and 26 aspirin-intolerant asthmatics. The cells were stimulated with Lys-ASA, N-formyl-methionyl-leucyl-phenylalanine (fMLP), or both fMLP and Lys-ASA, in a buffer containing IL-3, and results compared with human leukaemia cell line (Hl-60) response to Lys-ASA. Cys-LTs were measured in cell supernatant fluids by ELISA. ASA had a rather week stimulatory effect on cys-LTs release in both groups of patients. Contrary to some previous studies, no significant differences were found between cys-LTs release by leucocytes from AIA and ATA, or by differentiated Hl-60 cells. Measurement of cysteinyl-leukotriene release by peripheral blood leucocytes pre-treated with aspirin has no value for diagnosis of AIA.

Adult↗
PubMedDate not supplied

Is aspirin "the weakest link" in cardiovascular prophylaxis? The surprising lack of evidence supporting the use of aspirin for cardiovascular disease.

It is currently fashionable to prescribe aspirin, long-term to people with or at high risk of vascular events due to atherosclerosis. There is a moderately conclusive evidence for a short-term benefit after an acute vascular event. However, there is remarkably little evidence that long-term aspirin is effective for the prevention of vascular events and managing side effects may be expensive. Reductions in nonfatal vascular events may reflect an ability of aspirin to alter cosmetically the presentation of disease without exerting real benefit. Cardiovascular medicine appears prone to fads and fashions that are poorly substantiated by evidence. The current fashion for prescribing aspirin is reminiscent of the now discredited practice of widespread prescription of class I anti-arrhythmic drugs for ventricular ectopics. We should learn from experience.

Aspirin↗
PubMed1994

Effect of various antithrombotic regimens (aspirin, aspirin plus dipyridamole, anticoagulants) on the functional status of patients and grafts one year after coronary artery bypass grafting.

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.

Acenocoumarol↗
PubMed1995

Early and late onset asthmatic responses following lysine-aspirin inhalation in aspirin-sensitive asthmatic patients.

Inhalation of aerosolized lysine-aspirin (L-ASA) has been described as an alternative diagnostic method in aspirin-sensitive asthma. To further understand the pathogenetic mechanism of aspirin-sensitive asthma, we performed L-ASA (Inyesprin) bronchoprovocation test (BPT) in 51 asthmatic patients (45 non-atopic and six atopic asthma). Twenty-six patients showed significant bronchoconstriction after the inhalation of L-ASA. Bronchoprovocation test produced immediate asthmatic responses in 13 cases as well as dual asthmatic responses in four cases, whose late onset asthmatic response was noted at 4-7 h after L-ASA inhalation. We conclude that L-ASA bronchoprovocation might be a useful method for the diagnosis and investigation of aspirin-sensitive asthma. However, L-ASA inhalation can also induce late onset asthmatic responses.

Adult↗
PubMed2005

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity.

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.

Administration, Oral↗