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J Allard

Publications and source records attributed to J Allard.

At least 19 recordsLinked to original sources
PubMed2002

Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer.

PURPOSE: To determine the effect of elevation of serum HER-2/neu on response to hormone therapy. PATIENTS AND METHODS: Seven hundred nineteen metastatic patients with estrogen receptor-positive (ER(+)), progesterone receptor-positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels. RESULTS: Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with non-elevated and 23% in 217 patients with elevated serum HER-2/neu levels (P <.0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with non-elevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P <.0001). CONCLUSION: Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.

Aged↗
PubMed2002

Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug.

An exclusive central site of action for the proerectile effect of apomorphine, including not only the brain but also the spinal cord, is supported by extensive experimental data. Assuming that the mechanisms of action of apomorphine are similar in humans and animal models, its use for the treatment of erectile dysfunction (ED) validates the emerging idea that erectile response could be enhanced by acting directly within the central nervous system (CNS). It also emphasized the key role of the dopaminergic system in the control of erection. As exemplified with the clinical development of apomorphine, targeting the CNS does not rule out the occurrence of undesirable side effects. Because the rare event of syncope induced by apomorphine is not well understood, further research should be conducted to explore its possible mechanisms. In clinical practice, however, approved doses of apomorphine SL are well tolerated. It is noteworthy that no modification of sexual desire was observed with apomorphine. Indeed, drugs acting within the CNS may more likely interact with sexual desire than peripherally acting drugs, and care should be taken to assess this point in the future. Although our knowledge of the control of penile erection by the CNS is restricted, there are many potential sites for CNS-acting ED drugs. New centrally acting therapy for ED should concentrate on receptor targets more specific to erectile command. Clinical efficacy of new centrally-acting compounds will assess the well-founded purpose of this rationalization.

Animals↗
PubMed2001

Does histologic grade have a role in the management of head and neck cancers?

PURPOSE: High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. RESULTS: There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). CONCLUSION: Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Aged↗
PubMed2001

Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people.

BACKGROUND: The administration of many drugs concurrently to elderly patients is a well-known problem in geriatrics and involves numerous risks. One way to reduce polypharmacy is to provide information to physicians in order to modify their prescribing practices. The main objective of this study was to evaluate the impact of an intervention program that targeted physicians with the aim of reducing the number of potentially inappropriate prescriptions (PIPs) given to elderly patients. METHODS: A randomized controlled trial was carried out among community-dwelling elderly people in Sherbrooke, Que. The participants were 266 patients over 75 years of age (experimental group: n = 136, control group: n = 130). A team comprising 2 physicians, a pharmacist and a nurse reviewed the list of drugs and the diagnoses of a subgroup of the experimental group in a case conference. Suggestions were formulated and mailed to the patients' physicians together with relevant scientific documentation justifying the recommendations. The main outcome measure was the number of PIPs. RESULTS: The mean number of PIPs per patient declined by 0.24 in the experimental group (n = 127) and by 0.15 in the control group (n = 116). The decline in PIPs was even larger in the experimental group that had case conferences (n = 80), in which the mean number of PIPs per patient declined by 0.31. However, this difference between the experimental group and the control group was not statistically significant in the intent-to-treat analysis. The number of drugs prescribed was not modified by the intervention, nor were the results of the global assessment of the patients' drug profiles. INTERPRETATION: This study suggests that the intervention program had no effect on the prescribing of PIPs.

Activities of Daily Living↗
PubMed2001

Covalent intermediate trapped in 2-keto-3-deoxy-6- phosphogluconate (KDPG) aldolase structure at 1.95-A resolution.

2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase catalyzes the reversible cleavage of KDPG to pyruvate and glyceraldehyde-3-phosphate. The enzyme is a class I aldolase whose reaction mechanism involves formation of Schiff base intermediates between Lys-133 and a keto substrate. A covalent adduct was trapped by flash freezing KDPG aldolase crystals soaked with 10 mM pyruvate in acidic conditions at pH 4.6. Structure determination to 1.95-A resolution showed that pyruvate had undergone nucleophilic attack with Lys-133, forming a protonated carbinolamine intermediate, a functional Schiff base precursor, which was stabilized by hydrogen bonding with active site residues. Carbinolamine interaction with Glu-45 indicates general base catalysis of several rate steps. Stereospecific addition is ensured by aromatic interaction of Phe-135 with the pyruvate methyl group. In the native structure, Lys-133 donates all of its hydrogen bonds, indicating the presence of an epsilon-ammonium salt group. Nucleophilic activation is postulated to occur by proton transfer in the monoprotonated zwitterionic pair (Glu-45/Lys-133). Formation of the zwitterionic pair requires prior side chain rearrangement by protonated Lys-133 to displace a water molecule, hydrogen bonded to the zwitterionic residues.

Aldehyde-Lyases↗
PubMed2001

Outcome of patients treated with cobalt and 6 MV in head and neck cancers.

BACKGROUND: Since 1992, we have been using a 6-MV linear accelerator instead of a cobalt machine. The aim of the study is to evaluate the impact of this on neck control, particularly on postoperative patients in which subcutaneous tissues are at risk. METHOD: A retrospective study including all of 1,452 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All stages and subsites of the head/neck were included. Local and neck control were evaluated by the Kaplan Meier method, and comparisons were made between the cobalt and the 6-MV subgroups with a subsequent Cox analysis. For neck control analysis, the postoperative patients were divided in low and high risk (extracapsular extension [ECE], >two nodes, or T4). RESULTS: Radical radiotherapy: A better local control (LC) is observed with 6 MV than with cobalt, but neck control was similar. Postoperative radiotherapy: A better LC is observed with 6 MV. In high-risk patients, the neck control was higher for the cobalt group (79%) vs 60% for the 6-MV group (p = .09 and .03 in a Cox model). CONCLUSION: In postoperative patients at high risk for neck relapse, cobalt seems to give a better neck control. We are currently doing a prospective study in which a bolus is added for half the treatment when patients at high risk for neck relapse are treated with 6 MV.

Adult↗
PubMed2001

Central nervous system agents in the treatment of erectile dysfunction: how do they work?

Drugs acting within the central nervous system (CNS) that reduce the sympathetic antierectile flow and enhance the parasympathetic proerectile flow to the penis may restore penile erection in cases of erectile dysfunction of both psychogenic and organic origin. The best characterized of such drugs is the dopaminergic agonist apomorphine, which acts on the hypothalamus and, perhaps, the autonomic nuclei in the spinal cord. Other drugs that target the CNS and have been registered and tested are the a(2)-adrenoceptor antagonists yohimbine and delequamine, the alpha-melanocyte-stimulating hormone agonist melanotan II, and the serotonin reuptake inhibitor trazodone. Androgens also may influence sexual behavior by acting within the CNS, notably by modifying the neurotransmitter system targeted by these drugs. Our knowledge of the mode of action of CNS drugs comes mainly from experiments on rodents. Consequently, explanations regarding the way they work in humans are only speculative.

Animals↗
PubMed2001

Nutritional assessment of the lung transplant patient: body mass index as a predictor of 90-day mortality following transplantation.

BACKGROUND: It is well documented that malnourished and/or obese surgical patients have increased morbidity and mortality post-operatively. Only a few studies investigating the effect of nutritional status on mortality are available pertaining to the transplant population. Since limited data are available on the nutritional status and its effects on mortality in the lung transplant population, we sought to ascertain whether there is an association between mortality and preoperative nutritional status. METHODS: We examined mortality during the first 3 months after transplantation. Patients were grouped by body mass index (BMI) categories as < 17 kg/m(2), 17 to < 20 kg/m(2), 20 to 25 kg/m(2) (reference group), > 25 to 27 kg/m(2), and > 27 kg/m(2). Additional risk factors retrieved from the pre-transplant records included age, gender, diagnosis, energy requirements, protein requirements, protein and caloric intake, and weight history. Logistic regression for univariate and multivariate analysis for mortality used recipient age, gender, disease category, pre-transplant cytomegalovirus (CMV) serology, transplant type (single or bilateral), and donor age, gender, and CMV serology. RESULTS: The likelihood estimates or odds ratios (ORs) of the risk of death within 90 days of lung transplantation for the BMI categories compared to the reference group were 3.7 for BMI < 17 kg/m(2) (p = 0.085), 1.6 for BMI < 17 to 20 kg/m(2) (p = 0.455), 3.5 for BMI > 25 to 27 kg/m(2) (p = 0.069), and 5.0 for BMI > 27 kg/m(2) (p = 0.003). CONCLUSIONS: In patients with a pre-transplant BMI < 17 kg/m(2) or > 25 kg/m(2) the risk of dying within 90 days post-transplant was increased. In patients with a pre-transplant BMI of > 27 kg/m(2) the risk was significantly higher in than the reference group.

Adult↗
PubMed2001

Spinal proerectile effect of apomorphine in the anesthetized rat.

Considering the presence of dopaminergic receptors in the lumbosacral spinal cord, we tested whether apomorphine could exert a proerectile effect by acting at the spinal level. Intracavernous (ICP) and blood pressures (BP) were measured in anesthetized rats. ICP rises were quantified (duration, percentage of ICPmaximum/meanBP (ICPmax/BPx100), area under ICP curve (AUC/BP) and sum of AUC/BP after intravenous (i.v.) and intrathecal (i.t.) injections of apomorphine alone or in presence of i.t. oxytocin (10 ng). Both 10 and 30 microg i.v. apomorphine dosings elicited erectile events evidenced by ICP rises. Upon the 30 microg i.v. injection, duration of ICP rises were increased from 25+/-10 to 69+/-18 s (P<0.001), ICPmax/BPx100 from 21+/-3 to 50+/-14% (P=0.001), AUC/BP from 3+/-1 to 14+/-6 s (P=0.002) and sum of AUC/BP from 5+/-7 to 34+/-35 s (P=0.021). Upon 30 microg i.t. injections of apomorphine at the lumbosacral level, the number of ICP rises was increased from 0.2+/-0.4 to 3.0+/-1.5, ICPmax/BPx100 from 16+/-9 to 43+/-12 and sum of AUC/BP from 1+/-3 to 31+/-15 s compared to vehicle injection (P<0.05 for all parameters). Injection of 30 microg i.v. or i.t. apomorphine non-significantly enhanced the number and amplitude of the ICP rises induced by 10 ng i.t. oxytocin. However, the enhancement of the amplitude of the ICP rises elicited by i.t. oxytocin was more pronounced with i.t. apomorphine than with i.v. apomorphine. These results suggest the existence of a spinal site of action for apomorphine which may (1) participate to generation of erection and (2) exerts a facilitator effect on erection of supraspinal origin.

Animals↗
PubMed2001

Dopamine and sexual function.

The use of the D1/D2 dopamine receptor agonist apomorphine SL for the treatment of erectile dysfunction provides a strong support in favour of a participation of the dopaminergic system in the control of sexual function. However, the exact involvement of dopamine in sexual motivation and in the control of genital arousal in humans is unknown. In contrast, experimental data suggest an implication of dopamine at all these stages of the copulatory behaviour in rodents. The release of dopamine at the level of the nucleus accumbens, which is innervated by the mesolimbic dopaminergic pathway originating in the ventral tegmental area, is positively implicated in the pre-copulatory or appetitive phase in male rats. There is also a permissive role in the copulatory or consumatory phase for dopamine released at the level of the median pre-optic area, which receives projection from the dopaminergic incertohypothalamic pathway within the hypothalamus. It is noteworthy that these participations of the dopaminergic system are not specific to sexual behaviour but rather reflect the more general involvement of dopamine in the regulation of cognitive, integrative and reward processes. Due to its role in the control of locomotor activity, the integrity of the nigrostriatal dopaminergic pathway is also essential for the display of copulatory behaviour. Somehow more specific to sexual function, it is likely that dopamine can trigger penile erection by acting on oxytocinergic neurons located in the paraventricular nucleus of the hypothalamus, and perhaps on the pro-erectile sacral parasympathetic nucleus within the spinal cord. The counterpart of such regulation of the genital arousal by dopamine has not yet been established in females. In conclusion, the central dopaminergic system is a key element of the control of sexual function.

Animals↗
PubMed2001

Vaginal physiological changes in a model of sexual arousal in anesthetized rats.

The understanding of the pathophysiology of female sexual dysfunction suffers from the lack of a convenient model for the study of female genital sexual response. In this study, systemic arterial blood pressure (BP) as well as partial oxygen tension, temperature, and blood engorgement of the vagina [using laser-Doppler flowmetry in arbitrary units (AU)] were measured in anesthetized, ovariectomized (1 wk before the start of the experiment) female rats. Vaginal sexual arousal was replicated by electrical stimulation of the pelvic nerve (PNS). PNS induced reproducible increases in the different vaginal parameters (from baseline value, respectively: 16 +/- 10 to 30 +/- 12 mmHg; 34.9 +/- 0.6 to 36 +/- 0.6 degrees C; 450 +/- 196 to 1,500 +/- 360 AU; P < 0.05, paired t-test) and BP (90 +/- 7 to 123 +/- 13 mmHg, P < 0.05, paired t-test). Vaginal vascular resistance was significantly decreased during PNS (from 0.23 +/- 0.15 to 0.08 +/- 0.02 mmHg/AU). Vaginal wall tension was also measured with a force transducer. PNS induced an increase in vaginal wall tension (1.0 +/- 0.2 g), followed by a decrease under the prestimulation value. Intravenous atropine sulfate (1 mg/kg) injection abolished the increase in vaginal wall tension without significantly affecting vaginal vascular resistance. Intravenous vercuronium bromide (2 mg/kg) injection abolished the decrease in vaginal wall tension. Concomitant electrical stimulation of the paravertebral sympathetic chain inhibited vaginal response induced by PNS. Electrical stimulation of the medial preoptic area of the hypothalamus induced a response qualitatively equivalent to PNS with a significant decrease of vaginal vascular resistance. These data support that vaginal contractions involve both smooth and striated muscles and indicate that neural control of vaginal sexual arousal have great similarities in male and female rats.

Anesthesia↗
PubMed2001

ACE inhibitor-induced angioedema of the intestine: Case report, incidence, pathophysiology, diagnosis and management.

A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema of the intestine (AIAI) occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound) is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

Abdominal Pain↗
PubMed2001

Dopamine and male sexual function.

The use of the D1/D2 dopamine receptor agonist apomorphine for the treatment of erectile dysfunction provides strong support in favor of a participation of the dopaminergic system in the control of sexual function. However, the exact involvement of dopamine in the control of sexual motivation and genital arousal in males is unknown. Experimental data in male rats suggested an implication of dopamine in sexual motivation as well as in copulatory performance. Specific tests allowing assessment of sexual motivation showed that the release of dopamine at the level of the nucleus accumbens (innervated by the mesolimbic dopaminergic pathway) and the medial preoptic area of the hypothalamus (innervated by the dopaminergic incertohypothalamic pathway) positively regulated the anticipatory/motivational phase of copulatory behavior. A permissive role of dopamine released at the level of the median preoptic area of the hypothalamus in the display of copulatory behavior has also been demonstrated. It is noteworthy that these participations of the dopaminergic system are not specific for sexual behavior but rather reflect the involvement of dopamine in the regulation of cognitive, integrative and reward processes. Because of its role in the control of locomotor activity, the integrity of the nigrostriatal dopaminergic pathway is also essential for the display of copulatory behavior. Somehow more specific to sexual function, it is likely that dopamine can trigger penile erection by acting on oxytocinergic neurons located in the paraventricular nucleus of the hypothalamus, and perhaps on the pro-erectile sacral parasympathetic nucleus within the spinal cord. In conclusion, central dopamine is a key neurotransmitter in the control of sexual function.

Animals↗
PubMed2001

Non-AT(1)-receptor-mediated protective effect of angiotensin against acute ischaemic stroke in the gerbil.

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.

Acute Disease↗
PubMed2000

Use of oligonucleotide arrays to analyze drug toxicity.

The advent of oligonucleotide arrays allows the simultaneous analysis of the expression of thousands of genes. This powerful technology, highly dependent on advanced analysis tools, can transform the level of information currently available on the mechanisms underlying drug-related toxicity. It is now possible to analyze the global transcriptional response to a drug and determine the global pathways associated with the effects of this agent. This analysis can be performed on samples from patients that developed a toxic effect, on cells exposed to the toxic agent, and in animal models of toxicity. Especially useful is the comparison of transcriptional responses in animals susceptible to drug-induced disease with those of genetically modified animals that are resistant to this effect. This analytic strategy allows the delineation of specific mechanisms relevant and specific to drug-induced toxicity and thus might lead to novel therapeutic interventions in these toxic reactions.

Animals↗
PubMed1999

Edg-2 in myelin-forming cells: isoforms, genomic mapping, and exclusion in Charcot-Marie-Tooth disease.

Edg-2 is an heptahelical receptor whose spatio-temporal distribution during rat brain development is consistent with a role in the control of myelination. We have now identified two splice variants of Edg-2 mRNA in rat brain that encode two receptor isoforms differing by a stretch of 18 amino acids in the NH2-terminal extracellular tail of the receptor. Prenatally (i.e., before oligodendrocyte myelination), the two variants detected by selective in situ hybridization are equally abundant, vary in parallel, and remain restricted to proliferative zones in the brain. Postnatally, the long isoform becomes predominant in myelinating structures, where its abundance increases sharply during the period of myelination. In the adult human brain, only the long variant was detected, while in situ hybridization showed it selectively expressed in the white matter and in clusters of cells showing features of oligodendrocytes of the temporal cerebral cortex. Consequently, the human Edg-2 gene was studied to assess its possible contribution in inherited neuropathies. The coding sequence was found to be contained in three exons and to map to chromosome 9q31.3-32 by using radiation hybrid panel and Yeast-Artificial Chromosomes. Two intragenic bi-allelic polymorphisms and a rare mutation were identified. As a first application to molecular genetic studies, they were used to exclude the Edg-2 gene in six families with phenotype of demyelinating Charcot-Marie-Tooth disease of unknown origin.

Adult↗
PubMed1999

Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and sodium homoeostasis in cirrhotic patients with refractory ascites.

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could potentially decrease systemic arterial vasodilatation, possibly due to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function and renal sodium handling were assessed in vasodilated cirrhotic patients with refractory ascites treated with a transjugular intrahepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement served as controls for the sodium handling effects of ursodeoxycholic acid. From 1 month post TIPS, seven patients were studied before, after 1 month of treatment with ursodeoxycholic acid (15 mg.day-1.kg-1) and at 1 month follow-up. Lipid peroxidation products were used as indices of its antioxidant effects. Ursodeoxycholic acid caused a significant reduction in sodium excretion in both groups (P<0.05). This, in the post-TIPS patients (urinary sodium excretion: 35+/-8 mmol/day at 1 month versus 93+/-21 mmol/day at baseline, P<0.05), was due to a significant increase in sodium reabsorption proximal to the distal tubule (P<0.05), without any significant changes in systemic, renal or forearm haemodynamics, or in liver function. No significant change in lipid peroxidation products was observed. We conclude that: (i) in cirrhotic patients with refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium retention in cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic acid in cirrhotic patients with ascites.

Adult↗