Non-invasive portography: a microbubble-induced three-dimensional sonogram for discriminating idiopathic portal hypertension from cirrhosis.

OBJECTIVES: The aim of this prospective study was to elucidate the efficacy of contrast-enhanced three-dimensional (3D) ultrasound with Sonazoid(®) (GF Healthcare, Oslo, Norway) as a non-invasive tool to discriminate idiopathic portal hypertension (IPH) from cirrhosis by demonstration of portal vein structure. METHODS: There were 16 patients: 11 with biopsy-proven cirrhosis and 5 with biopsy-proven IPH. Intrahepatic right portal vein images were taken by 3D ultrasound from 1 min after the injection of Sonazoid (0.0075 ml kg(-1)). Portal vein appearances were compared between 3D ultrasound and percutaneous transhepatic portography (PTP) by four independent reviewers. Sensitivity, specificity and area under the receiver operating characteristic curve (Az) of the images were used for the diagnosis of cirrhosis/IPH, and interimaging, inter-reviewer and interoperator agreement were examined. RESULTS: Sensitivity, specificity and Az of PTP for the diagnosis of cirrhosis/IPH were 63.6%/100%, 100% and 0.9 (0.71-1.0) by Reviewer I and 90.9%/100%, 100% and 1.0 by Reviewer III, respectively. Similarly, sensitivity, specificity and Az of 3D ultrasound for diagnosis of cirrhosis/IPH were 54.5%/80%, 100% and 0.96 (0.84-1.0) by Reviewer II and 72.7%/80%, 100% and 0.97 (0.9-1.0) by Reviewer IV, respectively. Diagnostic agreement between PTP and 3D ultrasound was good between Reviewers I and II (κ=0.793) and good between Reviewers III and IV (κ=0.732). Inter-reviewer agreement was good between Reviewers I and III for PTP diagnosis (κ=0.735), and good between Reviewers II and IV for 3D ultrasound diagnosis (κ=0.792). Interoperator agreement of diagnostic results was good (κ=0.740). CONCLUSION: Non-invasive visualisation of intrahepatic portal vein structure by contrast-enhanced 3D ultrasound with Sonazoid may have the potential to discriminate IPH from cirrhosis.

Therapeutic effect of balloon-occluded retrograde transvenous obliteration for gastric varices in relation to haemodynamics in the short gastric vein.

The aim of this study was to elucidate the relationship between the therapeutic effect of balloon-occluded retrograde transvenous obliteration (B-RTO) and haemodynamic features in the short gastric vein (SGV) in patients with gastric fundal varices (GV). The subjects in this retrospective cohort study comprised 34 patients who had moderate- or large-grade GV with the SGV both on retrograde venography and Doppler ultrasound. The diameter, flow velocity and flow volume in the SGV measured by Doppler ultrasound before B-RTO with 1 h balloon occlusion were compared with the therapeutic effect. Embolisation of GV was achieved in 30/34 patients (88.2%): 27 by initial B-RTO and 3 by second B-RTO. Flow velocity and flow volume in the SGV before B-RTO were significantly lower in the 27 patients with a complete effect on initial B-RTO (7.19+/-2.44 cm s(-1), p = 0.0246; 189.52+/-167.66 ml min(-1), p = 0.002) than in the 7 patients with an incomplete effect (10.41+/-5.44 cm s(-1), 492.14+/-344.94 ml min(-1)). Neither endoscopy nor contrast-enhanced CT had recurrent findings of GV in the subject during the follow-up period (94-1440 days; mean, 487.2+/-480.5 days). In conclusion, haemodynamic evaluation of the SGV using Doppler ultrasound may be useful for the prediction of the therapeutic effect of B-RTO.

Application of percutaneous ultrasound-guided treatment for ultrasonically invisible hypervascular hepatocellular carcinoma using microbubble contrast agent.

AIM: To evaluate the efficacy of contrast-enhanced ultrasound for the localization of ultrasonically invisible hypervascular lesions in the liver to facilitate percutaneous ultrasound-guided treatment. MATERIALS AND METHODS: Forty patients with 47 ultrasonically invisible hypervascular lesions (5-20mm) diagnosed on contrast-enhanced computed tomography were enrolled in the retrospective study. Contrast-enhanced ultrasound (CEUS) with Levovist was performed to localize the lesions both in the early phase and liver-specific phase. Diagnosis of was confirmed by percutaneous needle biopsy where feasible, and on the basis of on treatment outcomes or changes in computed tomography findings in those not amenable to biopsy. RESULTS: Thirty-two lesions were diagnosed as hepatocellular carcinoma (HCC). Contrast-enhanced ultrasound localized hepatocellular carcinoma in 24/32 (75%) lesions, the mean diameter (15.1+/-4.9mm), as measured using computed tomography, being significantly larger than that of the remaining eight lesions (10.5+/-2.1mm). Ultrasound-guided treatment was performed in 19 of the 24 lesions, and transarterial chemoembolization (TACE) was applied for the other five lesions because of difficult percutaneous access. Five of the eight non-visualised lesions were treated by transarterial chemoembolization, and the other three by surgical resection. The beneficial effect of CEUS was significantly greater when the reason for poor initial visualisation was the coarse liver architecture (17/17) than when it was due to adverse location (seven of 15, p<0.005). Fifteen of the CT-detected hypervascular lesions were considered to represent false positives for HCC, based on their behaviour during follow-up. CONCLUSION: Contrast-enhanced ultrasound with Levovist facilitates the application of percutaneous ultrasound-guided treatment by improving localization of ultrasonically invisible hypervascular hepatocellular carcinomas in the liver.

Effects of sesquiterpenoids from "Oriental incenses" on acetic acid-induced writhing and D2 and 5-HT2A receptors in rat brain.

Six sesquiterpenoids, namely jinkoh-eremol, agarospirol, alpha- and beta-santalols, dehydrocostus lactone and costunolide, isolated from oriental incenses inhibited acetic acid-induced writhing in mice. The incidence of writhing produced by jinkoh-eremol, alpha-santalol and costunolide were revealed by administration of naloxone (mu-, kappa- and delta-antagonists). Inhibitory activities of alpha-santalol on opioid receptors were shown only by the delta antagonist, but not by the mu- and kappa-antagonists. The delta2-antagonist, but not the delta-antagonist, inhibited the activity of alpha santalol. The mechanism of inhibitory activity on the opioid receptor by alpha-santalol was different from that of morphine. Alpha-santalol was shown to be the most potent of the six as an antagonist of dopamine D2 and serotonine 5-HT2A receptor binding. The effect of alpha-santalol, was the same as that of chlorpromazine as an antipsychotic agent, although alpha-santalol was less potent than chlorpromazine.

Effect of jinkoh-eremol and agarospirol from agarwood on the central nervous system in mice.

Agarwood (Jinkoh in Japanese), one of the Oriental medicines, is used as a sedative. The benzene extract of this medicine showed a prolonged effect on the hexobarbital-induced sleeping time, and hypothermic effects in terms of rectal temperature, a suppressive effect on acetic acid-writhing, and a reduction of the spontaneous motility in mice. By repeated fractionation, oral administration in mice, and pharmacological screening, the active principles, jinkoh-eremol and agarospirol, were obtained from the benzene extract. They also gave positive effects on the central nervous system by peritoneal and intracerebroventricular administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased by them, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-administered mice. Therefore, jinkoh-eremol and agarospirol can be considered to be neuroleptic.

Effect of dehydrocostus lactone and costunolide from Saussurea root on the central nervous system in mice.

Saussurea root (Mokko in Japanese; root of Saussurea lappa, Compositae) is an aromatic stomachic and sedative in Oriental medicine. Four extracts of saussurea root were obtained by successively extracting with benzene, chloroform, methanol and water. Each of these extracts was tested for effects on the central nervous system (CNS) of mice by intraperitoneal administration, i. e. potentiation of hexobarbital sleeping time, body temperature alterations, antinociceptive effects, and spontaneous locomotor activity changes. The benzene extract was the most active and was then separated further into five fractions, 1,2,3,4, and 5 by column chromatography. Fraction 2 was shown to be the most active in the aforementioned assays. From this fraction dehydrocostus lactone and costunolide were isolated as the CNS active constituents. They were both active by the intraperitoneal, intragastric and intracerebroventricular routes of administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased following their administration, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-treated mice. These results show that dehydrocostus lactone and costunolide can be considered as neuroleptics by resemblance of their pharmacological activities to chlorpromazine.

Effect of α-santalol and ß-santalol from sandalwood on the central nervous system in mice.

Sandalwood (Byakudan in Japanese; Santalum album L.) is used as a popular sedative in Oriental medicine. Extracts of the wood of Santalum album were obtained by successively extracting with benzene, chloroform, methanol and water. Each of these fractions was tested for activity on the central nervous system of mice following intraperitoneal administration, i.e. potentiation of hexobarbital sleeping time, body temperature alterations, antinociceptive and spontaneous motor activity changes. The benzene extract was active in these assays and was then separated further into fractions 1, 2 and 3. Fraction 2 was shown to be the most active in the aforementioned assays, α- and ß-Santalols were isolated from this active fraction as the major CNS active constituents. They were both active by the intragastric and intracerebroventricular routes of administration. Thus, it can be considered that α- and ß-santalols contribute to the reputed sedative effect of sandalwood preparations in Oriental medicine. Additionally, α- and ß-santalols significantly increased the levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid and/or 5-hydroxyindoleacetic acid in the brain of mice, and chlorpromazine did the ones of homovanillic acid and 3,4-dihydroxyphenylacetic acid. These results showed that α- and ß-santalols could be considered as neuroleptic by resemblance to the pharmacological activities of chlorpromazine.

Effects of agarwood extracts on the central nervous system in mice.

Agarwood (Jinkoh in Japanese) is an Oriental medicine for use as a sedative. Neuropharmacological studies have been conducted with the extracts of petroleum ether, benzene, chloroform, and water from agarwood (Aquilaria sp.; probably Aquilaria malaccensis Benth.) in mice. The benzene extract showed a reducing effect in spontaneous motility, a prolonging effect on hexobarbiturate-induced sleeping time, a hypothermic effect in terms of rectal temperature, and a suppressive effect on acetic acid-writhing by oral administration. Fr. 1 of the three fractions which were obtained from the benzene extract by column chromatography was found to produce more positive effects on these neuropharmacological tests than the original benzene extract. These facts suggest that the benzene extractable compounds of agarwood possess potent central nervous system depressant activities.