Biomedical subjects
Publications and source records attributed to A Pradalier.
Thirty migraine without aura patients between attacks, 10 other during a migraine without aura attack and 30 normal subjects without headache were studied for platelet size and volume distribution using a new quantitative automated hematology analyzer (Coulter STKS). Platelet histograms, platelet counts and mean platelet volume were not significantly different in the three populations.
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Controlled studies of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of migraine attacks or for the prophylactic long-term treatment of migraine are reviewed herein. A large number of NSAIDs have been tested against a placebo or reference drug, including aspirin, indomethacin, mefenamic acid, tolfenamic acid, flufenamic acid, ibuprofen, flurbiprofen, fenoprofen, naproxen and sodium naproxen, diclofenac and lornoxicam. For the treatment of acute attacks, published studies found that the NSAIDs were significantly more effective than the placebo and at least as effective as the reference drugs. Adverse effects were absent or mild in this indication. Studies of NSAIDs as prophylactic treatment of migraine attacks are less numerous but also point to the value of this approach. However, long-term use of NSAIDs is associated with side-effects, mainly involving the gastrointestinal tract.
Alveolar macrophages from patients with asthma accumulated less cyclic adenosine monophosphate when these macrophages were exposed to isobutyl methylxanthine, salbutamol, or prostaglandin E2, compared to cells from control subjects without asthma, and the degree of the hyporesponsiveness was related to the severity of asthma. In addition, a significantly lower adenylate cyclase activity was observed in crude membrane fractions of macrophages from the group with asthma in the presence of salbutamol and prostaglandin E2. The refractoriness observed in patients with asthma is thus not accounted for by a specific beta-adrenergic desensitization at the adenylate cyclase receptor level but should rather be explained by a cyclic adenosine monophosphate-dependent postreceptor mechanism.
Many platelet abnormalities have been described in migraine, but they are now regarded as secondary phenomena rather than primary causative factors. In this study, we attempted to assess the presence of bioamine-releasing factors in the plasma of patients with common, non-dietary migraine. Blood samples were collected from 17 such patients, either during attacks (n = 9) or during attack-free periods (n = 8). Ten healthy volunteers served as controls. Release experiments were performed by adding 1 volume as controls. Release experiments were performed by adding 1 volume of migraineur's platelet-poor plasma to 1 volume of either control's whole blood (histamine release) or isolated platelets (catecholamines or serotonin release). Endogenous unconjugated bioamines were measured in whole blood and in isolated platelets from migraineurs' blood collected during and between attacks. We also measured plasma levels of histamine and of unconjugated and conjugated serotonin and catecholamines, as well as the inhibition of serotonin uptake and labelled serotonin release from controls' platelets in the presence of migraineurs' plasma collected during or between attacks. The results obtained suggest the presence of two plasma bioamine-releasing factors: a histamine-releasing factor present in migraineurs' blood during and between attacks, and a catecholamine and serotonin releasing factor present only during attacks in migraineurs' platelet-poor plasma. The latter factor is thermolabile and dialysable, with an apparent molecular weight lower than 16 kd. Gel-filtered fractions of semi-purified catecholamine-serotonin releasing factor induced the same events as the migraineurs' platelet-poor plasma from which they were obtained.
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The efficacy and safety of long-acting propranolol (LA.P), 160 mg once-daily, in the prophylactic treatment of migraine have been tested against placebo in a multicentric, double-blind, randomized study. The two groups are compared in a parallel manner over a treatment period of 12 weeks, following a 4-week placebo run-in period. Fifty-five of the 74 patients who entered the trial were included at the end of the run-in period. Forty-one patients completed the study. None of the 14 patients who withdrew from the study did so because of side effects. The statistical analysis was done according to the "intention to treat" principle. LA.P was significantly more effective than placebo in reducing the frequency of migraine attacks (p = 0.01 by variance analysis). LA.P reduced the average number of monthly crises by 48% on day 84. There was a slight but significant reduction of the systolic blood pressure and heart rate in the erect position, but there was no significant difference between LA.P and placebo regarding either the number of complaints or the number of side effects elicited out of a 17-item questionnaire. None of the observed side effects led to a withdrawal from treatment.
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Plasma pharmacokinetics of a single IV dl-propranolol dose (8 mg) were investigated in 12 obese subjects (mean +/- SD: 110.3 +/- 20.4 kg; 198.7 +/- 32.5% of ideal body weight) and compared with those of 12 healthy subjects (66.7 +/- 6.8 kg; 94.5 +/- 7.8% of ideal body weight). In obese subjects plasma alpha-1 glycoprotein acid concentrations and propranolol protein binding capacity did not differ significantly from control subjects. When compared with controls, obese subjects showed a significant increase (P less than .01) in AUC (161.0 +/- 67.0 vs 109.6 +/- 23.1 hr.micrograms/L), and significant decreases (P less than .01) in Vss (208.9 +/- 71.9 vs 318.6 +/- 91.8 L), V beta (234.3 +/- 70.4 vs 340.7 +/- 89.1 L), and total clearance (57.5 +/- 18.3 vs 75.9 +/- 15.4 L/hr). Elimination half-life was similar for the two populations (3.5 +/- 0.9 hr in obese subjects vs 3.1 +/- 0.9 hr in controls). Therefore, neither lipophilicity of propranolol nor drug plasma protein binding can explain these data. Altered hepatic function and tissue blood flow in obese subjects are proposed as an explanation for the decrease in total clearance and volume of distribution.
Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).
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Calcium ions are involved in many activities of cells, especially muscle contraction, mediator release and enzyme activities. It has been suggested that regulation of the cellular calcium could be important in the pathogenesis of asthma. In several studies, the efficiency of calcium antagonists on basophil degranulation and on asthma that is induced by pharmacological drugs (histamine, metacholine) or by exercise or allergens, has been investigated. A few studies on long-term treatment of asthma with calcium antagonists have been published. It seems that there is a place for the use of calcium inhibitors in the treatment of asthma, but it remains to fix the dosages and routes of administration and to identify the most effective products.
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