Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study.

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

BACKGROUND: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. METHODS AND RESULTS: Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. CONCLUSIONS: Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.

Simultaneous intracoronary ultrasound and Doppler flow studies distinguish flow-mediated from receptor-mediated endothelial responses.

Abnormalities in vascular endothelial function, which occur early in atherosclerosis, may play an etiologic role in the development of the disease or represent a marker for the extent of atherosclerosis. Endothelial dysfunction, usually characterized by demonstration of decreased endothelium-dependent vasorelaxation, may be a sensitive and specific method to detect vascular disease in its earliest stages. In this context, separation of abnormalities in receptor-mediated and flow-mediated endothelium-dependent vasodilatory responses may allow for the most accurate characterization of endothelial dysfunction. In 35 patients undergoing routine annual cardiac catheterization after heart transplantation, changes in epicardial lumen area and coronary blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously using an intravascular ultrasound (IVUS) catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed for distinction between receptor-mediated and flow-mediated endothelium-dependent vascular responses. Peak flow with the endothelium-independent resistance vessel dilator adenosine occurred at 18+/-2 sec; the maximal lumen area response occurred later, at 43+/-11 sec (P < 0.001). Acetylcholine, an endothelium-dependent small- and large-vessel vasodilator, caused an immediate increase in both flow and lumen area, but a second peak of dilation was observed, and maximal area occurred 46 sec after maximal flow (54+/-14 vs. 100+/-26 sec, P < 0.001). Simultaneous IVUS and Doppler flow measurements after infusion of vasoactive agents allows for distinction between and evaluation of the relative contribution of agonist-mediated and flow-mediated responses, which may offer important and unique insights into coronary endothelial function.

Discordant epicardial and microvascular endothelial responses in heart transplant recipients early after transplantation.

BACKGROUND: Cardiac allograft vasculopathy represents the leading cause of death in heart transplant recipients who survive more than 1 year. Functional endothelial abnormalities are sensitive measures of the early development of cardiac allograft vasculopathy, but the relative importance of large and small coronary vessel abnormalities has not been evaluated. The purpose of the study was to distinguish between large and small coronary endothelial dysfunction in patients early after heart transplantation and to test the hypothesis that microvascular endothelial responses can be preserved in the presence of epicardial endothelial dysfunction. METHODS: Changes in epicardial lumen area and coronary artery blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously by use of an intravascular ultrasound catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed distinction between large and small coronary vascular responses. In 19 patients studied early after transplantation, adenosine (16 and 32 microg), acetylcholine (5.4 and 54 microg), and nitroglycerin (200 microg) were infused, with continuous intravascular ultrasound imaging and Doppler velocity measurements. RESULTS: Acetylcholine induced paradoxical epicardial vasoconstriction in 12 of 19 patients (73% +/- 6% of baseline); vasodilation occurred in 7 (108% +/- 3%). In spite of this constriction, coronary artery flow increased in all 19 patients, to the same extent in patients with constriction and those with dilation (239 +/- 26 vs 193 +/- 20, p = 0.38). Adenosine and nitroglycerin increased area (107% +/- 1% and 112% +/- 3%) and flow (258% +/- 17% and 197% +/- 11%) in all patients. None of the area or flow responses correlated with the degree of intimal thickening. CONCLUSIONS: Acetylcholine increased coronary artery flow early after transplantation, indicating preserved microvascular responses in spite of epicardial vasoconstriction. Simultaneous measurement of area and velocity responses, by permitting evaluation of the relative contribution of epicardial and microvascular vessels, may offer unique insights into coronary endothelial function.

Sudden death in idiopathic dilated cardiomyopathy.

Approximately 30% of deaths among patients with IDCM are sudden. Although ventricular tachyarrhythmias are responsible for many of these deaths, bradyarrhythmias may also play a significant role. Patients with a previous history of sustained ventricular arrhythmias are at high risk for sudden death. In patients without prior symptomatic ventricular arrhythmias a history of unexplained syncope, severely impaired right ventricular hemodynamics, frequent spontaneous ventricular ectopy or NSVT, and inducible SMVT may help identify those at greatest risk of dying suddenly. With the exception of angiotensin-converting enzyme inhibitor therapy, attempts at pharmacologic prevention of sudden death have had limited efficacy. The implantable defibrillator offers promising results in survivors of previous sustained ventricular arrhythmias; its prophylactic use in other high-risk subgroups is the subject of active investigation.

[Evaluation of reduction of NSAID consumption after local treatment with a heparin-heparinoid combination in patients with osteoarthritis]. / Indagine sulla riduzione del consumo di FANS dopo terapia locale con un'associazione eparina-eparinoide in soggetti sofferenti di gonartrosi.

The efficacy of treatment with a heparin-glucuronilglucosaminoglycane association for external use was tested, in a double blind design, on clinical symptomatology and consumption of analgesic drugs (FANS) in patients affected with painful osteoarthritis of the knee. In the course of a 3-week treatment, the following parameters were evaluated: a) concerning the symptoms, intensity of spontaneous pain and of pain induced by both passive mobilization of the joint and walking; b) concerning the analgesic treatment, reduction of FANS consumption (expressed as percentage of basal dose) and of intensity of side effects. In the FANS + heparin-glucoronilglucosaminoglycane-treated group, the following were found with respect to the control group: a) higher reduction of pain intensity, statistically significant as far as pain on walking is concerned and higher increase in passive mobility of the joint; b) notable reduction of FANS consumption and intensity of side effects. The possible therapeutic mechanisms are discussed on the basis of both the characteristics of the employed drugs and the pathophysiology of painful osteoarthritis of the knee.

[Behavior of cardiorespiratory parameters in ischemia induced in the lower limbs. I) Monolateral ischemia]. / Comportamento di alcuni parametri cardiorespiratori in ischemia provocata degli arti inferiori. I) Ischemia monolaterale.

The subject of present research has been to study the effects of ischemia determining pain and cardiorespiratory modifications observed during and after isometric contraction of a quadriceps muscle subjected to a constant load. Therefore, in the same lower limb used for the previous test; an ischemia has been caused and protracted for the same amount of time. During and after the test the pain's intensity, VE, HR and VO2 have been noted. The obtained results have been subjected to statistic survey which has not proved significant variations of the studied cardiorespiratory parameters. Moreover pain has not arise during the test. A supposition that in those conditions only a little quantity of active metabolites can, be made. They conclude, therefore, that ischemia is a modest component in the cardiorespiratory modifications' determinism obtained with a test of isometric contraction of a quadriceps muscle subjected to a constant load.

[Behavior of cardiorespiratory parameters in ischemia induced in the lower limbs. II) Prolonged bilateral ischemia]. / Comportamento di alcuni parametri cardiorespiratori in ischemia provocata degli arti inferiori. II) Ischemia bilaterale protratta.

On the aim to evaluate the influence of ischemia in the modifications of some cardiorespiratory parameters during and after an isometric contraction of he quadriceps muscle subjected to a constant load, the authors have been studied the behaviour of VE, VO2, HR and intensity of pain on subject which has had ischemia on both lower limbs. The results have been used for a statistic survey. During the test any VO2 meaningful variations have not been observed, while a VE and HR linear increase has been noticed. Furthermore pain has not appeared. Absence of pain, HR decrease and fast VE and VO2 increase, has been observed after the test. They conclude that a large area of ischemia for a sufficiently long time produce a small variations in some of the cardiorespiratory parameters studied. It is so prove that muscular work and not the ischemia is the principal component in the production of metabolites that cause the pain and also the cardiorespiratory modifications.