Postmarketing surveillance of zopiclone in insomnia: analysis of 20,513 cases.

The subjective response to the prescription drug zopiclone, an hypnotic agent belonging to the cyclopyrrolone family, was assessed under the usual conditions of prescription of an hypnotic in general practice. The study included 20,513 insomniac outpatients with at least two of the following symptoms: sleep onset latency longer than 1 hour, more than two nocturnal awakenings, early morning awakening 1 hour or more before scheduled time, total sleep time of less than 6 hours, complaint of tiredness on awakening. Insomniac patients were treated with zopiclone and followed for 21 consecutive days within the context of a follow-up surveillance study. The population was predominantly female (62.6%), and the mean age was 52.3 years. The dosage of zopiclone prescribed at the inclusion visit was 7.5 mg per day in 87.5% of the cases and 3.75 mg per day in 10.5%. A total of 93.8% of the patients completed the survey. Spiegel questionnaire improved during the 21-day survey, and 9.2% of the patients reported at least one adverse event that led to treatment discontinuation in only 2.8% of the population. No serious or unexpected adverse events were reported.

Treatment of acute hepatitis C with interferon alpha-2b: early initiation of treatment is the most effective predictive factor of sustained viral response.

AIM: To evaluate the efficacy of early interferon alpha-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison. PATIENTS: Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus. RESULTS: There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1-7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 +/- 31 days) than in relapsers or non-responders (88 +/- 52 days) (P = 0.016). CONCLUSIONS: Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.

Cardiac beta-adrenoceptor sensitivity and Parkinson's disease.

Certain clinical manifestations of Parkinson's disease (PD) (speech or/and balance disturbances) are not linked to brain dopamine deficiency. The purpose of the present study was to search for a possible relationship between those so-called "non-dopamine-dependent" extrapyramidal manifestations and the sensitivity of cardiac beta-adrenoceptors. Fourteen patients aged 51 to 69 were included in the study after having given their informed consent. Any factor or pathology susceptible to modify receptor sensitivity entailed exclusion. In the absence of a reference model for measuring the reactivity of central beta-adrenoceptors, a computation of the isoprenalin dose necessary to increase the resting heart rate by 20 bpm was used as an index for beta-adrenergic system reactivity. In addition to that test, other parameters were recorded: disease duration, motor status scale (Columbia), some cognitive functions (MMS and image differed recall). The cardiac beta-receptor decrease in reactivity to isoproterenol is correlated to PD duration (r = 0.8, P less than 0.001). Conversely, the sensitivity of these receptors appeared to be unrelated to the extrapyramidal severity of the disease, hence to the degree of the so-called "non dopamine-dependent" disturbances. Furthermore, such results raise the meaning of the impairment of peripheral aminergic receptors in the cognitive disturbances linked to ageing and/or PD.

[Ten years of clinical experience with clozapine about 170 patients]. / Dix ans d'expérience clinique de la clozapine portant sur 170 patients.

The authors describe a clinical trial of 170 patients who received clozapine over a ten year period between September 1989 and September 1999. It is a retrospective study, describing individual responses. Each patient was his own control before and with treatment. The study also compared individuals within the group of patients whose treatment was stopped and those whose treatment was continuing at the time of the study. Data was collected by analysing all patients' records and by direct enquiry of prescribers. Diagnosis was according to DSM IV criteria. Assessment included: socio-epidemiological data (sex, age, marital status and family situation, education, military and professional status, level of benefits and social support); data related to the illness (age of onset, age at first contact with a psychiatrist, diagnosis, level of hospital contact); data concerning prescriptions of drugs (indications, average dose, duration of treatment, side effects, reason for stopping and other drugs taken at the same time); 170 patients were prescribed clozapine: 96 of them were continuing to take clozapine at the time of the study while 74 patients had stopped. The characteristics of the two groups are described. They show the severity of the illnesses concerned: early onset of illness and early psychiatric care, the absence in many patients of a partner or family, their low level of employment, high dependence on social assistance. Concerning diagnostic criteria, the range of diagnoses included mostly paranoid schizophrenia, then unclassified schizophrenia then schizoaffective disorders. The indication of clozapine prescription was in the majority of the cases (87%) an inefficiency of classical neuroleptic therapy. The average dose was 401 mg per day: 388 mg for the group continuing treatment; 417 for the group which had stopped their treatment. For the patients who continued taking clozapine, the average time of treatment was just over 4 years, with a maximum of 110 months. The tolerance of clozapine was good, with 35% not suffering any side effects. Neutropenia was the commonest side effect (4.1% - a higher incidence than previously reported with one case only of agranulocytosis (0.59%). The other adverse effects were in accordance with known data: sedation affected 22.4% of patients; hypersalivation 13.5%; postural hypotension 7.6%; malocclusion 7.6%; weight gain (>5 kg) 7.1%. Treatment was stopped for side effects in 17.1% of patients; for ineffectiveness in 14.7% and 3% of patients died during treatment (their death attributed to clozapine) from seizures, intestinal obstruction or agranulocytosis. Clozapine significantly reduced the need for other associated psychotropic drugs. 25.3% of all patients were on monotherapy when on clozapine compared with 6.5% before (31.2% compared with 3.1% for those patients continuing treatment). The need for supplementary medication to reduce side effects was much less. However 22% of patients taking clozapine at the time of the study are still on an anticholinergic drug. On the basis of the analysis of 5 successive terms of treatment lasting 12 months, we have shown that for each patient: clozapine significantly reduces the length of hospitalisation compared with standard neuroleptics; it allows for out patient management and continuing integration in the community; the critical length of treatment for the group of patients studied with regard to the need for hospitalisation is 18 months. For patients whose treatment with clozapine was stopped, we noted that with the continued input from the team of carers even after clozapine was stopped, patients who had been seriously ill for long period of time continued to improve.

[Complete neuroleptic withdrawal in patients with schizophrenia with intense symptoms and resistant to treatment]. / Sevrage neuroleptique complet chez des patients schizophrènes présentant une symptomatologie intense et résistant au traitement.

We report 2 studies evaluating the effects of a complete and progressive neuroleptic withdrawal on the symptomatology of 2 groups of 10 young chronically ill schizophrenic inpatients. In a preliminary open study, we compare the psychiatric symptomatology during a 4-week-period before the beginning of withdrawal and during a similar period following the end of withdrawal. We observe the significative improvement of the blunted affect, the deterioration of an aspecific psychiatric symptomatology (including irritability, excitement, hostility) and the non-modification of the specific schizophrenic symptomatology (in its 3 main components: positive signs, negative signs, disorganization). The second study (a double blind one) reports the effects of a complete neuroleptic withdrawal maintained during a longer period (8 weeks): 1. The improvement of the blunted affect is transiently observed during the 2 first weeks after the end of withdrawal but not after this time. 2. The deterioration of the aspecific psychiatric symptomatology by opposition to the non-significative modification of the specific schizophrenic symptomatology is a fact confirmed by this second study. Even if we can not exclude that the influence of neuroleptic withdrawal on the specific psychotic symptoms may require a longer time frame than 8 weeks to detect, this dichotomic evolution raises the problem of the specific action of neuroleptics in this particular category of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The HepCar registry: report on a one-year registration program of hepatocellular carcinoma (HCC) in Belgium. What is daily practice in HCC?

INTRODUCTION: Due to a rise in HCV induced liver cirrhosis, hepatocellular carcinoma becomes more prevalent in Western European countries. The HepCar registry is an initiative in which patients with hepatocellular carcinoma, their treatment and follow up are registered. MATERIALS AND METHODS: Belgian physicians were asked to report all new cases of hepatocellular carcinoma which were seen between January 2003 and December 2003. Reporting was done on a voluntary basis. Data reported were: demographic figures, the nature of the underlying liver disease, presentation characteristics of the tumour, laboratory findings and choice of therapy. Every six months, a reminder was sent to determine survival. RESULTS: 131 patients (94 male/37 female) were reported. Mean age was 63 years +/- 13. Underlying liver disease was HCV (n = 54, 41%), HBV (n = 22, 17%), alcoholic liver disease (n = 39, 30%) and miscellaneous (n =16, 12%). Diagnosis of hepatocellular carcinoma was made by surveillance in 47 (36%) patients. After logistic regression, survival was 5 times better for patients inside the Milan criteria (one lesion less than 5 cm in diameter or less than 3 nodules each less than 3 cm in the absence of vascular invasion and metastasis). DISCUSSION: Tumours inside the Milan criteria have a better survival. The majority of the patients have an underlying cirrhosis as background for the development of a HCC.

TIPS for refractory ascites: neither hemlock nor panacea. The Montreal experience and review of the literature.

Refractory ascites worsens the end-stage course of decompensated cirrhosis. Transjugular intrahepatic portasystemic shunt (TIPS) has been proposed to treat this condition with erratic success, inducing controversial reports on the risk-benefit ratio associated to this technique. In order to assess the usefulness of TIPS for this indication, this paper updates some definitions concerning the refractory ascites. We also analyze the main complications of TIPS and review some physiopathological pathways, taking peculiar interest in the Montreal experience.

Endoscopic therapy of Barrett's oesophagus: critical review.

Barrett's oesophagus is known as one of the most important risk factor of oesophageal adenocarcinoma. Because of the increasing incidence of these latter, many endoscopic methods such as argon plasma coagulation, photodynamic therapy or endoscopic mucosal resection are now in evaluation in order to eradicate Barrett's oesophagus or to treat dysplasia and early cancers arising from this metaplasia. The aim of this paper is to comment these techniques and discuss their usefulness.

Chronic lymphocytic leukemia with portal hypertension and without liver involvement: a case report underlining the roles of increased spleno-portal blood flow and "protective" sinusoidal vasoconstriction.

We report the case of a 72-year-old woman with well-controlled chronic lymphocytic leukemia (CLL) and splenomegaly who developed portal hypertension with bleeding oesophageal varices in the absence of liver fibrosis or regenerative nodular hyperplasia at surgical wedge liver biopsy. The hepatic venous pressure gradient (HVPG) was elevated and splenectomy resulted in both its normalisation and the regression of oesophageal varices. This case shows the potential for an increased spleno-poral flow to generate severe portal hypertension likely through a "protective" sinusoidal vasoconstriction.

Pharmacology of the memory process.

Rather than reviewing once again the published literature on drugs which are capable of modifying the memory process, the authors stress the methodological difficulties which impede the development of such products. At the moment, substances which act on neurotransmission systems, and in particular cholinergic and gabaergic agents, seem to be good candidates. The choice of the molecule to be studied in man depends on the neurochemical physiopathology of the memory disorder which one seeks to correct. For this reason, one tries to select an animal model of memory which is closest to the clinical situation pertaining to man on which the tested molecule might act favorably.

Oesophageal self expanding metal stents. Preliminary report about covered and non-covered types.

OBJECTIVE: The aim of this study was to evaluate the effectiveness and complications rate of covered and non-covered self expanding metal stents in the palliative treatment of oesophageal dysphagia. DESIGN: In this retrospective non-randomized study, we evaluated 11 non-covered and 17 covered stents of different types. RESULTS: Grade of dysphagia and improvement after treatment were similar in both groups, all the seven fistulas were sealed by covered stents. Covered stents seem to be safer regarding the rate of life-threatening complications and reinterventions. In contrast to published studies, bleeding was our major complication with death related in half of these patients. Aorto-Oesophageal fistula was proved by autopsy in two of them. CONCLUSIONS: Covered stents lead to less drawbacks than non-covered ones and seem to be recommended in the palliation of oesophageal dysphagia even in the absence of fistula.

[Unexpected origin of recurrent ascites: apropos of 2 cases]. / Origine inattendue d'une ascite récidivante: á propos de 2 cas.

The authors report the cases of two patients suffering from ascites attributed for several years to a non pericarditic aetiology. The first patient presented with a diagnosis of right cardiac failure secondary to a right myocardial infarction. Cardiac catheterisation, magnetic resonance imaging and transoesophageal echocardiogram allowed to establish the diagnosis. In the second case, ascites was attributed to cirrhosis. Presence of pericardial calcifications, visible on a chest X-Ray led to suspect constrictive pericarditis. In both cases, ascites contained a high protein level. A pericardectomy allowed a favourable outcome in both cases. Thus, a diagnosis of constrictive pericarditis must be evoked in face of ascites of unclear origin and a normal cardiac size.

Osseointegration of Brånemark fixtures using a single-step operating technique. A preliminary prospective one-year study in the edentulous mandible.

The aim of the present prospective clinical study was to analyze the feasibility of inserting Brånemark fixtures according to a one-stage procedure including transmucosal healing and to subsequently evaluate the predictability of osseointegration as well as the potential of such implants for stabilizing complete overdentures in the edentulous mandible. Five patients (2 women, 3 men), completely edentulous in the mandible and with a mean age of 60 years, volunteered for this study. Two fixtures of various length (10-20 mm) and 3.75 mm in diameter were inserted in the lower canine regions. A standard surgical procedure including a midcrestal incision was used. After the placement of the fixtures, healing abutments, which are normally used during second-stage surgery, were inserted instead of the usual cover screws. Three months after implant placement a clinical and radiographic examination was performed to confirm the presence or absence of osseointegration of the fixtures prior to exchanging the healing abutments with the spherical attachments. Finally, different clinical (Plaque Index, Bleeding Index, probing depth, Periotest mobility) and radiographic (bone loss, peri-implant radiolucency) parameters were recorded 9 months after loading of the fixtures by means of a complete mandibular overdenture, retained by two ball attachments in the canine regions. All fixtures were perfectly stable (mean Periotest values of -2) and presented favorable peri-mplant soft tissue conditions, and no patient was complaining about any particular symptom. As far as retention and stability of their implant supported overdenture was concerned, the participants without exception considered the therapeutic result as being perfectly adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

The rationale for using ursodeoxycholic acid in chronic liver disease.

The authors make a review of the literature and of their personal experience about the possible mechanisms of action and the beneficial therapeutic effects of ursodeoxycholic acid in primary biliary cirrhosis. They postulate that owing to its hydrophilic properties, ursodeoxycholic acid is more efficiently absorbed by the ileum than the other bile acids, so replacing the other bile acids in the bile acid pool, and that ursodeoxycholic acid is less toxic for hepatocytes than the other bile acids accumulating in the plasma and is also a choleretic.

Mesenterico-left intrahepatic portal vein shunt: original technique to treat symptomatic extrahepatic portal hypertension.

UNLABELLED: MESENTERICO-LEFT INTRAHEPATIC PORTAL VEIN SHUNT: Original technique to treat symptomatic extrahepatic portal hypertension. OBJECTIVE: Revascularization of the intrahepatic portal system as decompressive surgery for chronic extrahepatic portal hypertension. SUMMARY BACKGROUND DATA: In patients with extrahepatic portal hypertension (portal trunk thrombosis in presence of a normal liver), shunt surgery is indicated when patient is bleeding from varices at a site not accessible for the endoscopist. Although surgical portal decompression is an efficient procedure, there is a risk of depriving the liver from the splanchnic venous flow and a risk of developing porto-systemic shunt related side effects. METHOD: A shunt was created between the superior mesenteric vein and the umbilical portion of the left portal vein. This technique allows to bypass the thrombosed portion of the portal vein but avoiding dissection of the cavernoma in the liver hilum and related risk of intraoperative hemorrhage. RESULTS: The procedure was successfully performed in one adult patient considered unshuntable in view of classic surgical procedures and in whom sclerotherapy was unsuccessful. This operation achieved an effective decompression of the splanchnic venous system. CONCLUSION: Rerouting the venous splanchnic flow through the liver was possible. It had the major physiological advantage of restoring the normal hepatic vascularization. It also avoided putting the patient at risk of developing porto-systemic shunt related side effects. This option should be considered when shunt procedures are indicated in patients with extrahepatic portal hypertension.

[Anxiolytic agents and hypnotic drugs in Bretagne. Pharmaco-epidemiological study]. / Les anxiolytiques et les hypnotiques en Bretagne. Etude pharmaco-épidémiologique.

A pharmacoepidemiological survey was carried out in a rural region of France (Brittany) with the help of 54 general practitioners, all of whom belong to a clinical research group. The aim of the survey was 3-fold: to determine the frequency (incidence and prevalence) of anxiolytic and hypnotic drug prescriptions, the sociological characteristics of these drug consumers, and the indications and reasons for prescribing this class of drugs. The population of hypnotic drug and sedative consumers was strikingly dominated by women, 60 years old and over, retired or without a profession. Prescription analysis revealed that these drugs were essentially benzodiazepines whose prevalence and incidence were 17 and 1.76%, respectively. A high frequency of prescription renewals (78%) and an elevated percentage of long-term treatments (more than 9 years) were also noted. Insomnia and dependence are the two main "risk factors" for drug treatments lasting more than one year.

Haemodynamic adaptation two months after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients.

BACKGROUND AND AIMS: In portal hypertensive patients, transjugular intrahepatic portosystemic shunt (TIPS) acutely increases cardiac output and exaggerates peripheral vasodilatation. It has been suggested that the worsened hyperdynamic state may progress to high output heart failure. The aim was to evaluate the acute and short-term haemodynamic adaptation to this procedure. METHODS: Systemic, splanchnic, and pulmonary haemodynamics were studied in 15 cirrhotic patients under stable haemodynamic conditions before placement of TIPS, then 15-30 minutes after and two months later. For inclusion in the final analysis, an uneventful post-TIPS at two months follow up and a stable portacaval gradient were required. The following variables were measured or calculated: portacaval gradient; cardiac index (thermodilution); systolic and diastolic mean arterial, atrial, pulmonary arterial, and wedged pulmonary capillary pressures; heart rate; and total peripheral and pulmonary vascular resistances. Blood flow in the shunt was measured using duplex Doppler ultrasound. RESULTS: The portacaval gradient decreased by 56% and remained stable thereafter. Shunt blood flow was unchanged when measured immediately after TIPS and two months later. Immediately after TIPS there was a pronounced increase in cardiac index (+32%; p < 0.05) in association with a decrease in peripheral and pulmonary vascular resistance (-21%; p < 0.05 and -14%; NS). Two months later, whereas the initial rise in cardiac index was attenuated, peripheral vascular resistances remained similar and pulmonary vascular resistances decreased further (-33%; p < 0.05) compared with immediate post-TIPS values. CONCLUSIONS: Hyperdynamic circulation worsened immediately after TIPS, with a progressive adaptation during follow up. The mechanisms of post-TIPS induced haemodynamic changes include an abrupt volume load resulting from splanchnic decompression and an increased delivery of gut derived vasodilators to the systemic circulation. The persistence of decreased peripheral and pulmonary vascular resistances despite the reduction in high cardiac output two months after TIPS suggests that vasodilatation is not solely a compensatory response to a TIPS induced increased preload. Vasodilatory substances shunted away from the liver probably play an important part in this phenomenon.

Treatment of refractory ascites using transjugular intrahepatic portosystemic shunt (TIPS): a caution.

Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic patients, who then require repeated large-volume paracentesis. In this prospective study we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4 +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients following TIPS. Ascites recurrence associated with shunt stenosis was observed during follow-up in eight patients; revision could be undertaken in five of them and resulted in good control of ascites. In responders, a marked decrease in plasma aldosterone and renin activity, a reduction in serum creatinine, and a rise in urinary sodium excretion were observed. Creatinine and inulin clearances improved significantly; PAH clearance remained unchanged. However, new-onset or worsening hepatic encephalopathy was seen in 14 patients. Severe disabling chronic encephalopathy occurred in five patients; it could be reversed successfully by balloon occlusion of the shunt in three. The cumulative survival rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control refractory ascites in a majority of patients but is associated with a high rate of chronic disabling HE. In addition, the survival rate is poor. Randomized trials are needed to evaluate the exact role of TIPS in the management of refractory ascites. It is unlikely to improve survival but can ameliorate quality of life in nontransplant candidates and be useful as a bridge to transplantation, in particular, to improve denutrition associated with longstanding tense ascites.

New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature.

A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities. To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31). Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia. This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym "cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and migraine" (CADASILM) is proposed to better describe this particular subvariety of CADASIL.

Changes in plasma endothelin-1 and Big endothelin-1 induced by transjugular intrahepatic portosystemic shunts in patients with cirrhosis and refractory ascites.

BACKGROUND/AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor that may be involved in the pathogenesis of splanchnic and renal hemodynamic changes associated with portal hypertension. The aim of this study was to measure the concentration of ET-1 and of its precursor Big endothelin-1 (Big ET-1) in the systemic circulation as well as in the splanchnic and renal venous beds and to evaluate changes after the relief of portal hypertension following transjugular intrahepatic portosystemic shunt placement. METHODS: Plasma concentrations of ET-1 and of Big ET-1 were measured in the vena cava, renal vein, hepatic vein and portal vein in ten patients with cirrhosis and refractory ascites before and 1-2 months after transjugular intrahepatic portosystemic shunt. The porto-caval gradient, creatinine clearance, plasma aldosterone and renin activity, as well as daily urinary sodium excretion were measured at the same time. RESULTS: The plasma concentration of ET-1 and Big ET-1, respectively, in peripheral blood of normal volunteers were 0.28 +/- 03 and 3.95 +/- 0.34 pg/ml; the concentrations of both peptides were higher in patients with cirrhosis, both in vena cava (0.61 +/- 0.14 and 10.01 +/- 1.47 pg/ml), hepatic vein (0.62 +/- 0.13 and 13.93 +/- 1.77 pg/ml), portal vein (1.21 +/- 0.12 and 17.84 +/- 1.98 pg/ml) and renal vein (0.76 +/- 0.12 and 14.21 +/- 1.55 pg/ml). Moreover ET-1 and Big ET-1 concentrations were more elevated in the portal vein than in the vena cava (+98% and +70%) and slightly higher in the renal vein as compared to the vena cava (+25% and +42%). After transjugular intrahepatic portosystemic shunt, a rise in creatinine clearance and urinary sodium excretion (+49%; and +53%) was observed together with a marked reduction in plasma aldosterone and renin activity (-59% and -49%). ET-1 and Big ET-1 concentrations remained unchanged in the vena cava whereas a significant reduction of ET-1 and Big ET-1 occurred both in the portal vein (-43% and -44%) and in the renal vein (-53% and -29%). Portal vein and renal vein concentrations of both peptides became similar to vena cava levels. CONCLUSIONS: Splanchnic and renal hemodynamic changes occurring in patients with cirrhosis and refractory ascites could be related to the production of ET-1 by splanchnic and renal vascular beds. This was abolished by transjugular intrahepatic portosystemic shunt, which could explain the exacerbation of systemic vasodilation and the improvement in renal perfusion observed after the procedure.