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Lactitol vs. lactulose in the treatment of chronic recurrent portal-systemic encephalopathy.

To compare the efficacy and patient acceptability of lactitol vs. lactulose in chronic recurrent portal-systemic encephalopathy (PSE), 25 cirrhotic patients with a history of repeated episodes of hepatic encephalopathy who required chronic administration of lactulose were included in a controlled cross-over clinical trial in which patients received, at random, lactitol (at an initial dosage of 10 g/6 h) or lactulose (15 ml/6 h, 66% w/v, containing 10 g of lactulose) during a 3 month period and then crossed-over to the alternative treatment for the following 3 months. Doses were adjusted to obtain two bowel movements per day. During the study period the daily protein intake was 40-60 g. Clinical and analytical data (including ammonia levels) were obtained, an EEG and the number connection test were performed and the PSE index was determined before treatment and monthly until the end of the treatment. No significant differences were found between the effects of lactitol and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better tolerated than lactulose (P = 0.02), the taste of which was assessed as being too sweet and provoking nausea. In conclusion, lactitol is a good alternative to lactulose for patients with chronic recurrent PSE, especially in those who do not tolerate the excessive sweetness of lactulose.

Clinical Trials as Topic↗

Beneficial effect of carbohydrate maldigestion induced by a disaccharidase inhibitor (AO-128) in the treatment of chronic portal-systemic encephalopathy. A double-blind, randomized, controlled trial.

BACKGROUND: The most widely used treatment of portal-systemic encephalopathy (PSE) is the administration of oral, non-absorbable disaccharides. Theoretically, the inhibition of intestinal disaccharidases should induce malabsorption of disaccharides and increase delivery of undigested carbohydrates to the colon, thus stimulating the effects of lactulose and other non-absorbable disaccharides (that is, lactitol and lactose). AO-128 is an N-substituted derivative of valeolamine, an aminocyclitol that selectively inhibits intestinal disaccharidases. This study was performed to investigate whether AO-128 could be used as adjuvant therapy for the treatment of mild PSE in cirrhotic patients. METHODS: A double-blind, randomized, controlled trial was performed in 35 cirrhotic patients with PSE. Patients were given a 2-week treatment consisting of AO-128 (2 mg three times daily) or an identical placebo. The following features of PSE syndrome were assessed in a semiquantitative fashion before and after I and 2 weeks of therapy: mental state, asterixis, number connection test (NCT), venous blood ammonia concentration, electroencephalogram (EEG), and overall PSE index (PSEI). More patients receiving AO-128 than patients receiving placebo showed >40% improvement in the PSEI (83% versus 35%; P < 0.05). The mean stool pH decreased from 5.8+/-0.3 to 5.5+/-0.3 (P < 0.004) after AO-128 treatment, whereas no changes were observed in the placebo group. The EEG and nitrogen balance did not show significant changes in any of the two groups. A significant improvement was seen in the NCT performance after AO-128 (from grade 2.0+/-1.04 to grade 1.25+/-0.87; P < 0.05). Seven patients treated with AO-128 developed diarrhea, as compared with none in the placebo group (P < 0.05). CONCLUSION: These results suggest that AO-128 may be useful in the treatment of PSE, although further studies are required to establish the benefit of AO-128 and determine adequate individual doses.

Cyclohexanols↗

[The portal system].

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Cardiovascular System↗

Transjugular intrahepatic portal systemic shunt for the management of symptomatic cirrhotic hydrothorax.

OBJECTIVE: To investigate the safety and effectiveness of performing transjugular intrahepatic portal systemic shunt (TIPS) for the management of symptomatic cirrhotic hydrothorax in patients with advanced cirrhosis. METHODS: TIPS was performed by standard technique after portal vein patency had been established by ultrasound. Portal-hepatic vein pressure gradient was determined before and after placement of the shunt. A portal-hepatic vein gradient of less than 12 mm Hg was the treatment goal. RESULTS: Five patients underwent TIPS placement over an 11-month period. Despite use of diuretics, the patients had required a median of seven thoracenteses (range 2-11) for control of symptoms preceding placement of the shunt. A TIPS was placed without serious complications in all five patients. In two patients, insertion of the shunt was associated with no further need for thoracentesis. The other three patients had recurrent need for thoracentesis. These three patients were found to have occluded shunts which were rendered patent by angioplasty and/or urokinase. Subsequently, two required no further thoracentesis, whereas, in the other patient, the need for thoracentesis was decreased dramatically. CONCLUSIONS: TIPS appears to be a safe and useful technique for the management of patients with symptomatic cirrhotic hydrothorax that is refractory to medical therapy. Recurrence of the pleural effusion after placement of TIPS may be an indication of shunt occlusion.

Adult↗

Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy.

PURPOSE: To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). METHODS: Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. RESULTS: After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. CONCLUSION: Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.

Aged↗

Arginine sensors in the hepato-portal system and their reflex effects on pancreatic efferents in the rat.

To investigate the possible existence of arginine sensors in the liver and their reflex effects, afferent discharges from the hepatic branch of the vagus nerve and efferent discharges from the pancreatic branches of the splanchnic and vagus nerves were recorded. Intraportal injection of arginine increased afferent discharge rate of the hepatic branch of the vagus nerve, slightly depressed the efferent discharge rate of the pancreatic vagal branch, and increased the efferent discharge rate of the pancreatic splanchnic branch. The results suggest the existence of arginine sensors in the hepato-portal system that exert reflex regulation of the pancreatic neuroendocrine system.

Animals↗

[Correlation between the width of lingual vein and the changes of hemodynamics of portal system in patients with primary liver cancer].

OBJECTIVE: To explore the correlation between the width of lingual varix and changes of hemodynamics of portal system in patients with primary liver cancer so as to supply the data for the forecast of portal hypertension by observing lingual varix. METHODS: The diameter of lingual vein (Dlv) was measured by vernier caliper as dependent variable, and the diameters and indexes of hemodynamics of portal vessels were measured by Doppler as independent variables, then a multipe stepwise analysis was performed. RESULTS: The diameters of portal vein (Dpv) and splenic vein (Dsv) entered the formula Dlv (mm) = 0.185 + 0.311 Dsv (mm) + 0.236 Dpv (mm) when the entry and removal values were alpha(in)=0.10 and alpha(out)=0.15, respectively. CONCLUSION: The width of lingual vein is closely correlated with the diameters of portal vein and splenic vein in patients with primary liver cancer.

Adult↗

[Changes of blood supply from portal system after transcatheter arterial chemoembolization in huge hepatocellular carcinoma].

OBJECTIVE: Blood supply changes of the portal venous system to the tumor mass before and after transcatheterarterial chemoembolization(TACE) in a series of 22 patients with huge hepatocellular carcinoma were monitored to study the necessity of intervention via portal vein. METHODS: Twenty-two selected patients with huge hepatocellular carcinoma were enrolled in the study. Elscint double helical CT was used to scan liver during the maximum concentration of contrast medium in portal venous system. CT Angiography and MIP(Maximum Intensity Projection) were used to image formation of the portal venous system. RESULTS: The technique of scan and image formation were excellent to evaluate the attribution of portal venous blood supply to HCC. The portal venous blood supply was mainly the tumor periphery distribution (P < 0.01). After treatment of TACE, the portal venous blood supply to tumor periphery increased significantly (P < 0.05), and some did appear signs of enriched blood supply around the tumor. Negative correlation between the degree of reduction in tumor and portal venous blood supply to the tumor periphery before TACE was evident. CONCLUSION: The attribution of portal venous blood supply to HCC was in the tumor periphery, and regression of tumor after TACE was affected by portal venous blood supply to the tumor, thus it is reasonable to suggest interventional therapy via portal vein.

Adult↗

Portal systemic shunt through the renal vein.

BACKGROUND: Despite the semi-routine use of color Doppler sonography for evaluating portal circulation abnormalities, there is a relative paucity of detailed color Doppler findings of portal systemic (P-S) shunt through the renal vein (P-SR shunt). METHODS: We reviewed the color Doppler findings of 18 patients with P-SR shunt to determine its clinical significance and appropriate scanning techniques for diagnosing accurately P-SR shunt. RESULTS: The splenorenal shunt was imaged as a highly tortuous vessel at the splenic hilum, which then coursed backward behind the spleen. Splenic vein flow was reversed or very slow. The gastrorenal shunt originated from the splenic vein, coursed backward, and joined the left renal vein. Flow direction in the splenic vein was always hepatopetal. The P-S shunt through the right renal vein originated from duodenal or jejunal varices, coursed posterolaterally, and joined the right renal vein at the renal hilum. CONCLUSION: Familiarity with these color Doppler findings will help increase the diagnostic confidence of P-SR shunt by color Doppler sonography.

Adult↗

[The formation of the insulo-acinar portal system in the pancreas of human fetuses].

In human fetuses 12-20-week-old peculiarities in creation and development of the pancreatic hemo-microcirculatory bed have been studied in connection of its incretory part formation. The vascular glomerulus begins to form on the 12th-14th week as transformation of capillaries of the exocrinic parenchyma into the glomerular capillaries, which, on their getting out of the glomeruli, turn into vessels. The latter participate in formation of the insulo-acinar portal system. Certain structures have been revealed for adaptation of an elevated volume of the blood stream in the glomeruli place, where the glomerular microvessels pass into the acinar anastomoses. The latter perform shunting of the glomerular capillaries with the arteriole, which brings blood, enriched in insular hormones, to distantly situating acinar cells.

Gestational Age↗

Effect of pentobarbital anaesthesia on intestinal absorption and hepatic first-pass metabolism of oxacillin in rats, evaluated by portal-systemic concentration difference.

The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the difference in the drug concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F(H)), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CL(H)) was significantly decreased, resulting in an apparent small change in CL-CL(H) which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in F(H). It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism.

Anesthesia↗

First-pass of GTS-21 on canine gut wall and liver determined by portal-systemic concentration difference.

To clarify the cause of the canine individual variability of plasma concentration after oral administration of GTS-21 [(E)-3-(2,4-dimethoxybenzylidene)-3,4,5,6-tetra-hydro-2,3'-bipyridine dihydrochloride], we evaluated the absorption ratio (F(A)), intestinal availability (F(G)), and hepatic availability (F(H)). The bioavailability (F) was evaluated from the ratio of the area under the plasma concentration versus time curves after oral and intravenous administration. Three isoflurane anaesthetised dogs were fitted with an electromagnetic flow probe attached to the portal vein and cannulated through the portal and the femoral veins. After intraduodenal administration of GTS-21, both plasma concentrations were determined simultaneously. F(A) x F(G) was calculated from the portal-systemic concentration difference taking into consideration the blood-plasma partition ratio. F(A) was calculated from the residual drug contents of the small intestine. F(H) was calculated by dividing F by F(A) x F(G). The F values were 0.072, 0.021, and 0.037, indicating an individual variability of ca. threefold. The F(A) values were close to 1, and the F(G) values ranged from 0.449 to 0.461. Accordingly, the F(H) values were estimated at 0.170, 0.047, and 0.083. GTS-21 was completely absorbed but lost by first-pass effects of passage through the gut wall and liver. The first-pass effect of liver is larger than that of the gut wall, and dominates the individual variability in plasma concentration.

Animals↗

Glycine sensor in the hepato-portal system and their reflex effects on pancreatic efferents in the rat.

We earlier reported the existence of vagal arginine, alanine, and leucine sensors in the liver which modulate amino acid-induced pancreatic hormone secretion. To determine the possible existence of glycine sensors in the liver and their reflex effects, afferent discharges from the hepatic branch and efferent discharges from the pancreatic branch of the vagus nerve were recorded. Intraportal administration of 0.1, 1, and 10 mM of L-glycine solution (0.1 ml) depressed the afferent discharge rate of the hepatic branch of the nerve in a dose-dependent manner, and increased the efferent discharge rate of the pancreatic vagal branch. The results suggest the existence of glycine sensors in the hepato-portal system that exert reflex regulation on the pancreatic vagus nerve activity.

Animals↗

[Portal hypertension in children. Follow-up after portal systemic shunts (author's transl)].

The retrospective study of 115 children in whom a successful portosystemic shunt was carried out for portal hypertension, provides the following conclusions: 1) Patency of the shunt must be checked by esophageal endoscopy, six months postoperatively. A patent shunt can be expected when the size of the spleen and/or thrombocytopenia improve in the early post-operative period. Early ultrasound examination is also very useful in that respect. 2) None of the children with extrahepatic portal vein obstruction or congenital hepatic fibrosis presented with clinical signs of portal systemic encephalopathy (PSE). 3) Eight of 30 children with cirrhosis presented with one or more clinical episodes of PSE. Some were transient allowing for a normal diet to be resumed later on. 4) It is thus advisable to give children with cirrhosis a low protein diet in the months after surgery. Protein content of the diet can usually be increased progressively over a period of one to two years. 5) Whenever splenectomy is necessary, it is mandatory to prevent pneumococcal infections with the pneumococcal vaccine and daily treatment with oral penicillin.

Adolescent↗