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Resume Un debat est en cours sur l’integration du jeu pathologique dans le spectre des addictions sur le modele de la dependance aux substances. Dans cette perspective, notre objectif etait de faire le releve systematique des similitudes et differences entre ces deux maladies, de les classer puis de les analyser, a partir de l’expertise de l’Inserm sur les jeux de hasard et d’argent. Les aspects communs releves portaient sur les caracteristiques epidemiologiques, les criteres diagnostiques du DSM-IV, l’association de ces troubles, leurs caracteristiques neurobiologiques, des cas de guerisons spontanees et les aspects communs des prises en charge. Les differences concernaient une prevalence du trouble de l’humeur plus elevee chez les joueurs pathologiques, les facteurs de risque intrinseques au jeu, les erreurs cognitives du joueur pathologique (notamment le chasing ), les specificites des therapies cognitivo-comportementales centrees sur ces erreurs et celles de la prise en charge sociale des joueurs pathologiques. Neanmoins, notre analyse critique de ces elements pourtant rapportes comme specifiques au jeu pathologique a mis en valeur des points communs avec la dependance aux substances. Les phenomenes de craving et de perte de controle non discutes dans l’expertise pourraient aussi constituer des elements cles en faveur du regroupement de ces troubles.

Resume Des lors qu’un nouveau medicament est susceptible d’etre commercialise, la question de l’evaluation du progres therapeutique se pose en deux temps. Tout d’abord quelle est la quantite de progres therapeutique attendu ? Ce premier temps necessite de confronter aux besoins therapeutiques les resultats issus des etudes cliniques sur lesquelles reposent l’autorisation de mise sur le marche, afin d’anticiper le progres therapeutique attendu. Ensuite survient l’evaluation du progres therapeutique effectif. Celui-ci s’inscrit dans le suivi de l’usage du medicament, et sera issu de donnees d’observations en population. Destine a etre confronte au pari et aux incertitudes initiales (en termes de benefice et de risque), ces objectifs et les methodes mises en oeuvre doivent etre determines avant que le medicament ne soit mis a la disposition de la collectivite.

When a candidate drug is likely to become available to prescribers and healthcare policy makers, evaluation of therapeutic progress moves forward in two stages. First, the level of expected therapeutic progress must be established. This first stage requires the determination of therapeutic needs and the comparison of these against the results of the clinical studies that will form the basis of the marketing authorisation of the drug. This determination helps anticipate the therapeutic progress that is attributable to the approved use of the new drug. The second stage of the process, the evaluation of the actual therapeutic progress, involves therapeutic drug monitoring and bases itself on observation. Since such observational data are intended to challenge the initial hypotheses and uncertainties (in terms of benefits and risks), goals and methods must be laid out before the drug becomes available to the general public.

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate since proven treatments are available. In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves.

Similarities and differences between pathological gambling and substance dependence: a clarification. A critical analysis of a French review of the international literature on gambling.The integration of pathological gambling in the spectrum of addictive disorders modeled by substance dependence is currently discussed.To perform a systematic review of the similarities and differences between pathological gambling and substance dependence, and to classify and analyze them, based on the data collected by a previously published French systematic analysis of the international literature on pathological gambling.We established a checklist of each comparison of pathological gambling with substance dependence within the report. Then, every entry was classified as similarity or difference, analyzed and discussed.Similarities retrieved were epidemiological characteristics (gender, age, socio-demographic characteristics of subjects), diagnostic criteria from DSM-IV (five criteria in common), frequent co-occurrence of pathological gambling and substance dependence, neurobiological and genetic characteristics, cases of spontaneous recovery, and similarities of therapeutic care. Differences retrieved were a more elevated prevalence of mood disorders and suicide among pathological gamblers, intrinsic risk factors related to gambling activity (delay between bid and result, gambling device, big win), cognitive distortion of pathological gamblers (notably chasing), specificities of cognitive behavioral therapies focused on these cognitive distortions, and specificities of social care of pathological gamblers.Pathological gambling shared many similarities with substance dependence, but also some differences. However, our critical analysis of these elements, reported to be specific to pathological gambling, showed significant commonalities with substance dependence. Also, the existence of key symptoms of substance dependence such as craving and loss of control in pathological gambling was not discussed in the review, although other data suggest a common ground. These could be key elements to group together pathological gambling and substance dependence within the addictive disorders.

A haptic system consists of an articulated mechanical structure with motors and position sensors, as well as embedded electronics allowing force feedback. It is driven by a haptic interface, which enables the user to interact with an image in a virtual reality application, through the sense of touch. Thus, it is a hybrid dynamic system, which contains subsystems with continuous dynamics and subsystems with discrete dynamics that interact with each other. This paper develops a hybrid dynamic system model of the system, which takes into account the different sampling periods of the desired regulation, and the interaction between continuous, switching and discrete subsystems. It is interesting when very short electrical transients coexist with very long mechanical ones.

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate. Rather, studies of superiority, equivalence, or non-inferiority have been recommended. Such studies require very large sample sizes, and the burden of osteoporotic fracture in a trial setting is substantially increased. Studies of equivalence cannot be unambiguously interpreted because the variance in effect of active comparator agents is too large in osteoporosis. If fracture studies are required by regulatory agencies, there is still a requirement for placebo-controlled studies, although perhaps of shorter duration than demanded at present.

The French drug surveillance system is characterized by: a network of thirty one regional drug surveillance centres, located to provide convenient proximity to health care professionals; a causality assessment method, compulsory for all persons involved in drug surveillance, to assess the causal relationship between an adverse effect and one or more drugs; if necessary, an additional evaluation of the causal relationship will be performed using pharmaco-epidemiology methods; a Technical committee and a National Commission of Drug Surveillance which centralize and assess all the data in order to provide a consensual advice to the relevant authorities on necessary measures, to prevent, or reduce a drug related adverse effect; in the case of an inquiry, the drug surveillance department of the pharmaceutical company and the network of regional drug surveillance centers will pool their data with the aim to exchange information and ideas.

Il aura fallu attendre 2010 pour que soit menée en France la première étude de prévalence des troubles liés à la pratique des jeux de hasard et d’argent [1]. Si cette enquête a indiqué que les problèmes de jeu touchaient environ 1,3 % de la population adulte, elle ne décrivait que partiellement les caractéristiques associées. Il est cependant essentiel de disposer d’informations pouvant expliquer qu’une pratique récréative devienne hors de contrôle. L’étude JEU a cette ambition. Impliquant 7 centres hospitaliers français, elle a débuté en 2009 et a permis de recruter 628 sujets ayant joué au moins une fois au cours de l’année écoulée, qui seront suivis pendant les 5 années suivantes. Répartis en 3 groupes (« joueurs non problématiques = JNP », « joueurs problématiques sans soin = JPNS » et « joueurs problématiques avec soins = JPS »), l’un des objectifs de cette étude est de comparer leurs caractéristiques respectives. Lors du suivi de la cohorte, l’évolution de ces variables sera mise en perspective avec l’évolution de la pratique et du recours à des soins spécifiques. Une partie des résultats issus de la description des 3 groupes sera présentée ici. Des régressions logistiques multivariées, comparant 2 à 2 les groupes, ont été réalisées. Elles indiquent que, par rapport aux JNP, les JP jouent plus fréquemment, ont un score de distorsions cognitives plus élevé et un score de détermination plus faible. Par rapport aux JPNS, les JPS sont plus jeunes, plus fréquemment actifs, plus nombreux à jouer sur Internet, avec un jeu pathologique plus sévère et un risque suicidaire plus important. Cette étude permet de dresser le tableau des joueurs, en particulier ceux pour lesquels la pratique devient problématique. Des hypothèses au sujet des facteurs favorisant et limitant l’accès aux soins sont discutées.

Si les points communs sont nombreux entre le poker et les autres jeux de hasard et d’argent (JHA), les professionnels du soin et de la recherche spécialisés dans le jeu pathologique sont de plus en plus nombreux à insister sur la nécessité de prendre en compte les spécificités de ce jeu, afin de mettre en place des actions de prévention et de soins plus adaptées et donc plus efficaces. Nous avons mis en place la cohorte multicentrique JEU qui a pour objectif principal d’explorer les déterminants des transitions de la pratique de jeu (émergence des problèmes de jeu, recours à des soins, rechute, etc.). Un objectif secondaire de cette cohorte était de décrire et de comparer les différents types de jeu de prédilection. Les résultats présentés ici concernent une régression logistique multivariée permettant de comparer les joueurs de poker (n = 78) aux autres joueurs de la cohorte (n = 537), dans deux sous-populations distinctes : les joueurs non problématiques et les joueurs problématiques. Les joueurs (problématiques ou non problématiques) de poker se distinguent des autres joueurs par un score d’illusion comportementale sur le jeu (GABS-attitude) plus élevé, une initiation au jeu plus précoce et une pratique du jeu moins ancienne. De plus, les joueurs non problématiques de poker se distinguent des autres joueurs non problématiques par une mise maximale en un jour plus élevée, un score de coopération (TCI) plus élevé et moins de troubles anxieux. Par ailleurs, les joueurs problématiques de poker se distinguent des autres joueurs problématiques par le fait de jouer plus sur Internet et un score de transcendance (TCI) moins élevé. Ces résultats seront discutés en termes d’implications pour la prévention, la recherche et les soins dans cette population particulière de joueurs.

In borderline and permanent hypertensives after rapid i.v. injection of dl-propranolol 0.2 mg/kg plasma levels were measured and were fitted to a two-compartment open-model. In borderline patients, characterized by a high basal cardiac output (CO), plasma levels were always lower than in permanent hypertensives. The biological half-life was reduced and the central volume of distribution, volume of distribution at pseudo-equilibrium and total clearance (TC) were markedly increased. In the overall population, there was a significant positive correlation between CO and TC. Rapid achievement of a predetermined plateau in each group constituted experimental proof of the validity of the two-compartment open-model for kinetic analysis of propranolol i.v. If kinetic parameters from permanent hypertensive were applied to borderline hypertensives a lower plateau was obtained. Thus, in so far as beta-blockade is related to plasma level of propranolol, an increased intravenous dose may be required in patients with high CO.

Total effective compliance, hemodynamic parameters, extracellular fluid volume, cardiopulmonary (CPBV) and total blood (TBV) volumes were determined in 32 men, including 14 normotensive controls and 18 sustained essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid Dextran infusion. In normotensive controls, compliance was 2.08 +/- 0.09 ml/mm Hg/kg and was positively correlated with plasma (r = 0.79) and extracellular fluid (r = 0.84) volumes. In hypertensives, compliance was significantly reduced (1.49 +/- 0.06 ml/mm Hg/kg; P is less than 0.001) and was correlated negatively with the CPBV/TBV ratio (r = -0.75) and positively with the plasma volume/interstitial fluid volume ratio (r = 0.84). These results suggest that in normotensives, there is a regulatory mechanism between volume and compliance and that this contributes to maintaining filling pressure and cardiac output within normal ranges. In hypertensives, the reduced compliance could participate in the maintenance of normal values of cardiac output and extracellular fluid volume by influencing the partition of intravascular and extracellular fluid volumes.

1. Resting plasma dopamine β-hydroxylase (DBH) activity and haemodynamic parameters were studied in untreated borderline (twenty-nine) and permanent (twenty-seven) essential hypertensive patients. DBH was also measured in sixty-three apparently healthy subjects. 2. Mean DBH values were not significantly different between the groups. 3. Cardiac output, cardiopulmonary blood volume and the cardiopulmonary blood volume/total blood volume ratio (CPBV/TBV) were significantly higher in borderline than in permanent hypertensive patients. 4. In borderline hypertensive patients, plasma DBH activity was directly correlated with diastolic arterial pressure and with values of cardiac output, cardiopulmonary blood volume and CPBV/TBV ratio. No such correlations could be observed in the permanent hypertensive group. 5. These results suggest that plasma DBH activities in borderline hypertension mainly depend on the sympathetic activity responsible for the haemodynamic variations. Contrariwise, plasma DBH activities in permanent essential hypertensive patients appear to reflect other factors.

Extracellular fluid volume (EFV), total blood volume (TBV), and renal indices were determined in 53 permanent essential hypertensive patients with normal renal function and balanced sodium intake and urinary output. In comparison with normal subjects, hypertensives had normal EFV values while TBV and the TBV/EFV ratio were significantly reduced (p less than 0.001). In hypertensives, a significant negative relationship (r = -0.40; p less than 0.005) was observed between the TBV/EFV ratio and diastolic arterial pressure. No correlation existed between TBV and diastolic pressure, whereas EFV (and also interstitial fluid volume) was positively related to diastolic arterial pressure (r = +0.41; p less than 0.005). Extracellular fluid volume and interstitial fluid volume were both directly correlated to the renal filtration fraction (r = +0.45; p less than 0.005). The study suggests that, in the disturbed partition of the extracellular fluid of hypertensives, changes in the interstitial space are involved and are related to variations in the renal indices.

A quality assurance system for clinical trials entails the definition, prior to the trial, of a number of procedures (the "good clinical practices") ensuring that it will be correctly conducted and the verification that these procedures have been respected. Setting up a clinical trial quality assurance system involving the manufacturer, university staff and public authorities should result in trials that are better performed. The role and responsibilities of each party are discussed, together with the consequences to be expected from the introduction of good clinical practices in France.

In experiments in which blood was cross-circulating in rats, the blood pressure of the recipient dropped while that of the donor rose, following the increase of the circulating blood volume, produced by infusion either of saline or blood. The phenomenon was almost imperceptible when binephrectomized animals were used. In experiments in which the blood-bathed organ technique was used, prostaglandin-like substances were detected, released during the rise of the blood pressure, produced by the same stimulus (the expansion), in anaesthetized rats. A significant difference was found between the prostaglandin-like substances detected using the blood-bathed organ technique, in normal rats (5.387 ng per ml of blood plus or minus 0.288 = SEM) and those detected in binephrectomized rats (3.202 ng per ml of blood plus or minus 0.330, p smaller than 0.025). The biologically active substances detected in 25 ml of blood collected during expansion, while the assay organs showed a prostaglandin-like activity, were found to have the chromatographic behaviour and the bioassay properties of PGA, PGE and PGF series. A great quantity of the biologically active substances, having the chromatographic behaviour and the bioassay properties of PGA, PGS and PGF was detected in the rat renal medulla. Sufficient quantities of the released prostaglandin-like substances could escape the pulmonary vascular bed in this species of animal. It was concluded that a great quantity of the released prostaglandin-like substances came from the kidney and their release by this particular mechanism suggested that they play an important homeostatic role on the blood pressure, blood volume, and sodium and water balance regulation.

A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (-18%) and lasted longer (12 h) after 60 mg than after 20 mg (-11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration--time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r = 0.61, p less than 0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.

The electrophysiological properties of Mexiletine were investigated by endocavitary His Bundle recording and programmed electrical stimulation of the heart in 30 patients. Differing dosage (2, 2.7 and 3.4 mg/kg) were given intravenously in 3 groups of 10 patients. The effects on the length of the sinus cycle, conduction intervals and cardiac refractory periods were observed and the following results obtained : 1. Sinus rhythm increased at all dosages but this effect was much more pronounced with 3.4 mg/kg dosage (--12.8% +/- 2.81% : : % shortening of sinus cycle with respect to the basal cycle +/- SD, p less than 0.005); 2. Atrioventricular nodal conduction time (A-H interval) decreased, the effect being more marked with the larger dose regimes; 3.His-Pirkinje conduction time (H-V interval) unaltered except in 3 cases where it increased by 5 ms after injection of 2.7 mg/kg; 4. Relative refractory period of His-Parkinje system shortened, this effect also being more pronounced with the larger doses ( --3.75 +/- 0.25% :2.7 mg/kg, p less than 0,001; -- 7 +/- 1.46% 3.4 mg/kg, p less than 0.005). In conclusion, the changes observed in the His-Purkinje system after mexiletine were similar to those of Lignocaine and Diphenylhydantoin. The drug also appears to have a marked vagal inhibitory effect as shown by the acceleration of the sinus rhythm and reduced atrioventricular conduction times.

The purpose of this study was to investigate the effectiveness and safety of enalapril in elderly people. A double-blind, randomized, placebo-controlled trial was carried out in 32 subjects aged from 75 to 97 years (mean: 86 years) with blood pressure values equal or superior to 160/90 mmHg. After 8 weeks of treatment with enalapril in doses of 20 to 40 mg/day, the systolic pressure was lowered from 190 +/- 16 to 151 +/- 19 mmHg (P less than 0.0001) and the diastolic pressure from 102 +/- 7 to 85 +/- 11 mmHg (P less than 0.0001). Systolic and diastolic pressures were also significantly reduced in subjects under placebo (from 183 +/- 16 to 165 +/- 21 mmHg, P less than 0.001; and from 101 +/- 9 to 91 +/- 13 mmHg, P less than 0.001, respectively), but the degree of reduction was significantly superior with enalapril (systolic: 39 +/- 25 vs 18 +/- 19 mmHg, P less than 0.005; diastolic: 17 +/- 13 vs 11 +/- 12, P less than 0.001); blood pressure was inferior to 160/90 mmHg in 67% of the subjects treated, as against 35% of those under placebo. Two patients under enalapril died: one on the 27th, the other on the 47th day of treatment. No relation could be established between these deaths and the drug, and this figure of 2 is not significantly different for the number of deaths expected over the same period in a population of that age-group. Among the patients under placebo, one had pulmonary embolism on the 34th day and another had a sudden increase in blood pressure on the 6th day, requiring discontinuation of treatment. It is concluded that enalapril administered alone is effective and well tolerated. Long-term studies are needed to find out whether this angiotensin-converting enzyme inhibitor is superior to a diuretic as initial treatment of arterial hypertension.

Cyclosporin is a nephrotoxic immunosuppressant metabolized in the liver and requiring drug monitoring. Numerous pharmacokinetic and pharmacodynamic drug interactions have occurred with this compound. Some of them are well substantiated while others are merely suspected. The major interactions must definitely be prevented of corrected, whereas the others need no more than careful drug monitoring.

The effects of a single oral dose of enalapril (20 mg) on blood pressure (BP), heart rate (HR) plasma renin activity (PRA) aldosterone (PA), converting enzyme inhibition (CEI) and enalaprilat (E, active metabolite) were investigated during 96 h in 3 groups of 5 hypertensive patients with (1) normal renal function (creatinine clearance: Clcr greater than 80 ml.min-1); (2) moderate chronic renal failure: 80 greater than or equal to Clcr greater than 30 ml.min-1; (3) severe chronic renal failure: 30 greater than or equal to Clcr greater than 10 ml.min-1. Results are as follows (mean +/- SEM): (Table: see text) CEmax: maximal plasma concentration; TEmax: delay corresponding to CEmax; TE 1/2: plasma elimination half-life; AUCE: area under plasma level versus time curve. a: p less than 0.01; b: p less than 0.001; versus (1). In the 3 groups, CEI reached 87-94% as early as the 3rd h; however, at 96 h, CE1 was higher in (3) than in (1) and (2): 77.6 +/- 3.3% versus 6.0 +/- 1.6 and 17.7 +/- 4.8 (p less than 0.001 respectively). In (3). PRA increased at the 1st h and remained elevated: at 96 h, delta PRA was + 3.0 +/- 2.9 ng.ml-1 -.h-1 in (3) versus + 0.10 +/- 0.06 and + 0.25 +/- 0.17 ng.ml-1.h-1 .n (1) and (2) [(3) versus (1): p less than 0.01]; delta PA was lower in (3): -4.56 +/- 2.01 ng. 100 ml-1 versus -0.54 +/- 0.31 and -2.50 +/- 0.38 ng. 100 ml-1 [(3) versus (1): p less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

The decrease of sympathetic activity by the beta-blocking drug, as demonstrated by the decreased electric activity of the splanchnic nerve and by the decreased urinary catecholamine reponse to tilt as well as by the decreased levels of plasma dopamine beta-hydroxylase exists not only in hypertension with elevated PRA but also in hypertension with normal or low PRA. In these latter cases the antihypertensive effect is better explained by the decrease in the sympathetic nervous system activity than by the decrease of PRA. This effect seems to be indirect and probably, as suggested by Lewis, as a result of damping sensory input to the central nervous system from the heart, whose capacity to respond to exercice and stress is blunted by beta-adreno-receptor blockade.

Fifteen patients with hypertension due to phaeochromocytoma and 35 controls with essential hypertension were studied to assess the diagnostic value of urinary and plasma biochemical determinations in phaeochromocytoma. In every case of phaeochromocytoma the urinary concentration of vanillylmandelate, metanephrines, or adrenaline plus noradrenaline was diagnostic of the disease irrespective of whether the patient was normotensive or hypertensive at the time. Plasma determinations of adrenaline and noradrenaline, however, gave falsely negative results on three occasions. These findings suggest that urinary biochemical determinations--particularly of metanephrines--are more reliable than plasma catecholamine measurements as a test for phaeochromocytoma. The test is particularly useful in patients with intermittent hypertension.

Plasma renin activity and extracellular fluid volume were determined in 34 normotensive and in 35 sustained essential hypertensive patients with normal renal function, balanced sodium intake and urinary output. In normotensives, plasma renin activity was negatively correlated to extracellular fluid volume (r = 0.54; p = 0.001). The 95% confidence limits of the normotensive curve was used as nomogram to classify the hypertensive patients into two groups: those (23 cases) that fell within the limits of the normal curve (group I) and those (12 cases) that were below these limits (group II). In comparison with group I, group II was characterized by: (i) similar values for age, blood pressure, inulin clearance and extracellular fluid volume and (ii) significantly but lower values (p less than 0.001) for plasma renin activity with maintenance of the relationship between extracellular fluid volume and renin. The study strongly suggests that (i) the hypertensives of group I had no abnormal regulation of the renin-angiotensin system in comparison with the control subjects and (ii) the hypertensives of group II had an extracellular fluid volume-renin relationship set for lower values of renin.