RESUMEN

Clinical benefit in oncology patients can only be derived from coordinated and successive experimental trials. The following consensus thus emerged from the working party: The assessment of tolerance during clinical trials requires the actuarial rate of acute adverse events (AE) to be registered and the development of epidemiological structures involved in long-term assessment of AE. Experimental trials have to be assessed according to descriptive epidemiological data (generated in France and Europe) and completed with observational studies on post-marketing medical practice. The principle of an a priori authorization given by the Afssaps for gene and cell therapy trials was legalised in October 2001. The working group spoke strongly in favour of authorizing early trials only validating the process, and for reasonable objectives in terms of viral security assessment of annex therapeutic products. With regard to the development of new antiproliferative agents, the active dose (or optimal biological dose) replaces the maximal tolerable dose. Early efficacy criteria could be biological and specific. With cumulative subacute rather than acute toxicity, these agents can not be properly evaluated with a short term benefit/risk ratio as is done for cytotoxic drugs. Elderly people constitute a fragile, heterogeneous and increasing population, in whom adequate assessment of anticancer agents is mandatory. It is important to promote controlled clinical trials in children and to systematically monitor them over a very long period of time. Only rare tumours may be considered as orphan situations. Finally, a list of all clinical trials conducted in oncology should be made by the Afssaps, with the help of the FNLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) who have already begun this work.

Asunto(s)

RESUMEN

As far as communication of the evaluation of risk benefit assessment of medications is concerned, validated and interpreted data only have to be taken into account. Free access to information by the public has to be considered seriously and there is now a real and strong demand. This situation has to be viewed in parallel with the huge development of websites communicating information on health issues. This report summarizes the discussion between the authorities and pharmaceutical companies and reports the different concrete proposals that emerged.

Asunto(s)

RESUMEN

'Alicaments' ('ali' for 'aliment' = 'food' in French, and 'cament' for medicament = drug), is an inappropriate term to designate a developing domain: functional foods, in other words health claims in nutrition. It is not easy to delineate the frontier between foods and drugs; this results in some regulatory problems. The key question is the evaluation of health claims. In this report, we synthesize the discussions of a workshop bringing together specialists from the food industry and nutritionists, scientists and representatives of public health departments.

Asunto(s)

RESUMEN

The availability of new drugs for Alzheimer's disease, with different pharmacological profiles, leads to a redefinition the relevant methodology for developing drugs in this indication, including the inclusion/exclusion criteria, the duration of the studies, and therefore, the relevant guidelines. This was the purpose of the Giens Round-table devoted to the new methodology for drug development in Alzheimer disease.

Asunto(s)

Asunto(s)

RESUMEN

Voluntary sequential ambulatory recording is a diagnostic method of recording per-critical electrocardiographs in symptomatic patients with the aid of a portable solid-state technology recorder. In order to assess the value of this technique in the detection of arrhythmias, a multicenter study was performed in 1,287 symptomatic patients suspected of having paroxysmal arrhythmias (palpitations in 86.5% of cases). The quality of the sequential ambulatory recording was judged to be good in 54.9% and mediocre in 40.2% of cases: only 4.9% of recordings were uninterpretable. This technique allowed identification of a cardiac arrhythmia related to symptoms in 42.5% of the 1,091 cases which were analysed; sustained supraventricular tachycardia (11.7%), ventricular extrasystoles (14.9%) and simple sinus tachycardia (9.5%) were the principal abnormalities. The per-critical recording was negative in 57.5% of patients, suggesting a purely functional origin of symptoms in these cases. Atrial fibrillation was more common in hypertensive patients (11.3% vs 5.5% in normotensives, p less than 0.01) as were ventricular extrasystoles (23.1% vs 13% in normotensives, p less than 0.001). Voluntary sequential ambulatory recording seems to be a technique well adapted to the detection of symptomatic arrhythmias and a useful complement to Holter recording.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

An ajmaline test was conducted in 120 patients with a history of disorders of consciousness : Adams-Stokes syndrome (n = 49), loss of consciousness (n = 42), or lipothymia (n = 29). Four types of response were observed after ajmaline : VH less than 80 ms (n = 63); VH between 80 and 100 ms (n = 19); VH greater than 100 ms (n = 17); distal block (n = 21). One hundred and fifteen of these patients were followed-up for from three to six years (mean 56 months). Pacemakers had been fitted in 46 of them. Atrioventricular block was eventually detected in 37 patients but was excluded in the other 78 cases, either because the syncope attacks did not recur or because another cause was demonstrated. The predictive value of the ajmaline test was confirmed by the subsequent course of the disorders. Based on only clinical findings, diagnosis was confirmed in 42 p. cent, excluded in 12 p. cent, and impossible to define in 46 p.cent of cases. After the ajmaline test, diagnosis was confirmed in 79 p.cent, excluded in 6 p.cent, and impossible to define in 15 p.cent. The risk of atrioventricular block can be evaluated as 1-6 p.cent when the increase in VH is less than 80 ms, 35.3 p.cent when the increase is between 80 and 100 ms, 62.5 p.cent when it is greater than 100 ms, and 100 p.cent when there is a distal block. The indications for fitting a pacemaker depend upon the results of this test. If contra-indications are respected (recent history of an infarct, cardiac failure, marked enlargement of the heart), complications are rare, being observed in less than 3 p.cent of cases.

Asunto(s)

Asunto(s)

RESUMEN

Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.

Asunto(s)

RESUMEN

Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases.

Asunto(s)

RESUMEN

Cardiac output (isotopic dilution method) and systolic time intervals were studied in 11 sustained and 8 borderline essential hypertensive patients, before and after intravenous administration of atenolol, a potent beta-blocking agent. Atenolol decreased significantly (p less than 0.01) cardiac output and heart rate. In borderline hypertensives, the preejection periods were significantly reduced. Atenolol prolonged the preejection periods more significantly (p less than 0.01) in borderline than in permanent hypertensives. Non invasive hemodynamic technics enabled the cardiac performance to be evaluated in hypertensives and the contribution of neurogenic factors in borderline hypertension to be estimated.

Asunto(s)

RESUMEN

1 Hepatic blood flow was determined before and during (+)- and (+/-)-propranolol plasma concentration plateaus in 19 patients with suspected renal hypertension and normal liver function. 2 Hepatic blood flow significantly decreased (P less than 0.001) during (+/-)-propranolol administration and remained unchanged during (+)-propranolol administration. 3 Hepatic extraction ratio was 74 +/- 1% (+/-)-propranolol and 79 +/- 2% for (+)-propranolol. 4 Total propranolol clearances were determined during the steady-state achieved by a constant infusion. A highly significant positive relationship was observed (r = +0.86; P less than 0.01) between hepatic blood flow and (+)-propranolol clearance. The slope of the curve was 1.05 +/- 0.27. 5 The result implies that the total clearance of (+)-propranolol constitutes an accurate estimation of basal hepatic blood flow in subjects with normal liver function.

Asunto(s)

Asunto(s)

RESUMEN

Blood pressure, renal blood flow, total blood volume (TBV), plasma renin activity, and vascular reactivities to angiotensin and norepinephrine were studied in 48 normotensive subjects and 106 essential, sustained, hypertensive patients with normal renal function, balanced sodium intake, and urinary output. A significant negative pressure-volume relationship was observed in normal subjects. Among the hypertensive patients, some were inside the 95% confidence limits of the normal curve and the others were above, indicating a disturbance in the pressure-volume relationship. A quantitative evaluation of the pressure-volume disturbance was proposed and discussed. The blood pressure of each hypertensive patient corresponded to two different blood volume values: the renal valve and the theoretical value extrapolated from the normal curve. The difference between the two values was called deltaTBV and was positive in hypertensive patients. The deltaTBV value was negatively correlated with the renal blood flow, the creatinine clearance, the plasma renin activity, and the vascular reactivities to angiotensin and norepinephrine (P less than 0.0001). The parameters were not correlated with the real blood volume. This study demonstrates quantitatively a pressure-volume disturbance in essential hypertension. This disturbance is strongly correlated with the renal function and the renin-angiotensin system changes.

Asunto(s)

RESUMEN

Central hemodynamics were determined in 202 men including 101 normotensive and 101 permanent essential hypertensive patients of the same age. Cardiac output was identical in the two groups while blood pressure and total peripheral resistance were significantly different. Strong differences between the two groups are revealed by a systematic correlation study: (i) correlations of blood pressure (with respectively heart rate and total blood volume) were significant in the normotensive group but not in the hypertensive group; (ii) correlations of cardiac output (with respectively heart rate and total blood volume) were significant in both groups; (iii) correlations of renal blood flow (with respectively cardiac output and blood pressure) were significant in the hypertensive group but not in the normo tensive group. This study provided evidence that the volume and neural pressure controls are impaired in hypertensive patients while the cardiac output control is maintained and, suggested the existence of adaptive mechanisms involving the kidney in the maintenance of normal cardiac output in permanent essential hypertensive patients.

Asunto(s)

RESUMEN

Cardiac output, cardiopulmonary (CPBV) and total (TBV) blood volumes, vascular reactivity to norepinephrine and dopamine B hydroxylase (DBH) were determined in 41 borderline hypertensives patients in comparison with 28 normal subjects. Cardiac output (P less than 0.001) and CPBV/TBV ratio (P less than 0.01) were significantly increased. The ratio was directly correlated to the pressor-response to norepinephrine (P less than 0.01) and the DBH level (P less than 0.005). The results suggest that sympathetic overactivity plays a dominant role in the cardiac output elevation of borderline hypertensive patients.

Asunto(s)

Asunto(s)

RESUMEN

The pressor-response to norepinephrine was determined in the whole body circulation of 15 normal subjects and 86 untreated essential hypertensive patients. The slope, the threshold-dose and the critical-dose were calculated from the log dose-response curve. In the overall population (101 subjects) a slight correlation (r = +0.20 less than 0.05) was observed between the basal diastolic arterial pressure and the threshold-dose. In contrast, highly significant parabolic correlations (r = +0.46 less than 0.00001) were observed between the diastolic arterial pressure and the slope or the critical dose. When diastolic arterial pressure was above 100 mmHg, the slope increased while the blood pressure increased. This result suggests either a decreased sympathetic tone or an adaptative structural change of the arterial wall. When diastolic arterial pressure was under 100 mmHg, the slope decreased while the blood pressure increased. This observation points to an enhanced sympathetic activity in mild blood pressure.

Asunto(s)