Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2

To determine the relationship between quantitative Doppler parameters of portal, hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG), variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we studied forty patients with proved alcoholic cirrhosis who underwent Doppler ultrasonography, hepatic vein catheterization, and esophagoscopy. The following Doppler parameters were recorded: time-averaged mean blood velocity, volume flow of the main portal vein flow, and resistance index (RI) of the hepatic and of the superior mesenteric artery. Doppler findings were compared with HVPG, presence and size of esophageal varices, and Child-Pugh class. There was a significant inverse correlation between portal velocity and HVPG (r = -.69), as well as between portal vein flow and HVPG (r = -.58). No correlation was found between RI in the hepatic artery or superior mesenteric artery and HVPG. No correlation was found between portal vein measurements and presence and size of varices. Severe liver failure was associated with lower portal velocity and flow. In patients with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither hepatic nor mesenteric artery RI, are correlated to the severity of portal hypertension and to the severity of liver failure.     

Microsurgical technique to improve the insertion of totally implantable arterial device (TIAD) in presence of hepatic artery anomalies

In order to achieve perfusion of both lobes of the liver for hepatic arterial infusion chemotherapy, several surgical techniques can be used when the right hepatic artery arises from the superior mesenteric artery. Three of these techniques (utilization of cystic artery, end-to-side anastomosis between the right hepatic artery and proper hepatic artery, and insertion of a fine-tipped special catheter in the right hepatic artery) often require microsurgery applications.     

Changes in intestinal vascular diameter during norepinephrine vasoconstrictor escape

The hypothesis that escape from norepinephrine-induced vasoconstriction in the intestine is due to relaxation of initially constricted vessels was tested in 18 anesthetized cats. Intestinal blood flow was measured by an electro magnetic probe on the superior mesenteric artery. Intestinal submucosal and muscle arterioles and small mesenteric arteries were studied by in vivo microscopy with an image-splitting technic. Continuous recordings of mesenteric flow and vessel diameter were made during the infusion into the superior mesenteric artery of norepinephrine (NE) at a rate of 1-2 mug/min for 3 min. Mesenteric flow decreased soon after the NE infusion began but then escaped. Microscopically, arterial constriction and escape were noted in submucosal, muscle, and mesenteric vessels with a time course similar to that for flow. Arteriovenous anastomoses were not seen. These findings support the hypothesis that escape from Ne-induced vasoconstriction is due to relaxation of initially constricted vessels.     

Changes in neurotransmitters in multiple sclerosis

PURPOSE: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using non-invasive in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. METHODS: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. RESULTS: With systemic i.v. (tail vein) infusion, the 19F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0-5.5 min), and then gradually decreased. The signal for the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) gradually increased to the sixth spectrum (0-33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion. CONCLUSIONS: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic arterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully.     

Lung resection after pneumonectomy for bronchogenic carcinoma

AIMS/BACKGROUND: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short-term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D-sorbitol (S-HCl). METHODS: Twenty-five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady-state, during constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S-HCI before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was directly measured at the level of the right (Er), where TIPS was applied, and of the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t-test for paired data. RESULTS: After application of TIPS, a substantial reduction was observed in PCG (12.1+/-4.2 vs 24.8+/-4.3 mmHg; p<0.001) and Er values (20.6+/-14.8 vs 57.5+/-22.3 %; p<0.001) but not El values (47.4+/-22.0 vs 53.4+/-21.4 %; p=0.178). S-HCl measured 120 min after TIPS opening was not statistically different from pre-TIPS values (389.2+/-212.1 vs 394.6+/-152.7 ml/min; p=0.892), although S-HCl variations in Child-Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). CONCLUSION: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.     

Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels

BACKGROUND: Decompression of extrahepatic portal hypertension by directly bypassing the thrombosed portal vein has never been reported in cases of children with idiopathic (or neonatal) portal vein obstruction and cavernoma. METHODS: Seven children (15 years or younger) with portal vein obstruction requiring surgical decompression (urgently in two cases), and in whom preoperative Doppler had shown that the intrahepatic portal branches were hypoplastic but free of thrombus, were included in a pilot study. The cavernoma was bypassed by interposing a venous jugular autograft between the superior mesenteric vein and the distal portion of the left portal vein. Patients received follow-up using routine clinical parameters, upper gastrointestinal endoscopy, and Doppler ultrasound. RESULTS: The mesenterico-portal bypass restored a direct (physiological) hepatopetal portal flow. The operation resulted in effective portal decompression as demonstrated by decrease of the pressure gradient, rapid regression of clinical signs of portal hypertension, and definitive control of bleeding. CONCLUSIONS:This study shows that direct bypassing of portal cavernoma is possible and results in effective portal decompression. Restoration of the hepatic portal flow is a major advantage compared with conventional surgical shunting procedures. This new technique is potentially applicable to two thirds of children with portal vein thrombosis and should be considered when shunting procedures are indicated.     

Giant cell tumour of the retropharynx

INTRODUCTION: Few pancreatic carcinomas (5-22%) are resectable at the time of diagnosis because this lesion is seldom diagnosed in an early stage. Unresectability is mainly due to the presence of metastases to the liver, peritoneum and lymph nodes and to tumor spread especially to the portal mesenteric trunk where it can invade, compress, reduce, or occlude the vessels. We investigated the diagnostic yield of multiplanar and 3D spiral CT in the assessment of pancreatic carcinoma resectability. MATERIAL AND METHODS: Twenty-seven patients with histologically confirmed pancreatic head cancer were submitted to spiral CT and color Doppler US in the Surgical Clinic I of the Bologna University. The examination results were correlated with the intraoperative findings of careful inspection and palpation and of US studies of the pancreatic mass and adjacent structures. The tumors were classified in relation to some CT parameters: tumor size (T), infiltration of the stomach (S) and/or duodenum, lymph nodes (N) or distant (M) metastases, involvement of vascular structures (V), particularly of portal or superior mesenteric vein, or superior mesenteric artery. Five grades of vascular involvement were considered. The results of these techniques were correlated with intraoperative findings from careful inspection and palpation and with US studies of the pancreatic mass and adjacent structures. RESULTS: Spiral CT revealed vascular involvement in 19 of 27 cases (70.4%): involvement of portal and superior mesenteric vein was found in 14 (73.6%), superior mesenteric vein was involved in 2 (10.6%), the portal vein in one (2%) and, finally the portal, superior mesenteric vein and superior mesenteric artery in 2 cases (10.6%). The spiral CT results were confirmed intraoperatively in 26 of 27 cases (96.3%); spiral CT did not reveal hepatic metastasis only in one case. Spiral CT with multiplanar reconstructions had very high specificity and sensitivity (100%) in the assessment of vascular involvement, while color Doppler US had the same specificity but lower sensitivity (84.2%). Spiral CT was less sensitive (80%) in the detection of liver metastases. CONCLUSIONS: We believe that spiral CT is currently the best technique for pancreatic carcinoma staging, providing useful information for correct surgical planning.     

Hepatic response to increased exogenous supply of plasma amino acids by infusion into the mesenteric vein of Holstein-Friesian cows in late gestation

The hepatic responses of late gestation, dry dairy cows to acute (6 h) infusions of an amino acid (AA) mixture (Synthamin; 0.0, 1.1, 2.2, 4.4, 8.8 and 17.6 mumol/min) into the mesenteric vein were determined. Neither blood flow nor O2 consumption across the portal-drained viscera (PDV) and liver was significantly altered by infusion. Similarly, there were no effects on net absorption, or hepatic removal, of acetate, propionate, butyrate or NH3. Glucose PDV appearance was unchanged but hepatic glucose production increased (P = 0.032) by 0.2 mumol/min per mumol/min of AA infused. Additional extraction of alanine, glycine (both infused) and glutamine (not infused) by the liver was sufficient to account for most of the extra C required for glucose synthesis. The N that would be liberated from these glucogenic AA would also account for a large proportion of the increase in urea-N produced in response to the AA infusion. This supports the concept of a correlation between gluconeogenesis and ureagenesis. Furthermore, the amide-N liberated from the extracted glutamine would contribute up to 0.17 of hepatic NH3 flux and assist in balancing N inputs into the carbamoyl phosphate and arginosuccinate entry points of the ornithine cycle. Rates of fractional extraction of the various AA by the liver were best fitted by linear equations, indicating that even at the highest rates of administration (approximately twice maximal physiological absorption) the transport systems were not saturated. Hepatic fractional extractions of infused essential AA were highest for methionine (0.83) and phenylalanine (0.87) with the lowest proportion removed observed for valine (0.25), leucine (0.30), lysine (0.31) and isoleucine (0.49). For the non-essential AA, the highest apparent fractional extractions were for glycine (0.73), arginine (0.79) and tyrosine (0.63) followed by alanine (0.54), proline (0.47) and serine (0.37). Hepatic removal of AA-N exceeded the increase in urea-N formation such that, at the highest rate of infusion, approximately 10 mmol/min of the extracted AA was apparently available for hepatic anabolism, more than is required to account for assumed increases in liver mass and export protein synthesis. Similarly, the amount of AA available for peripheral tissue protein gain, when assessed against phenylalanine supply as the limitation, would be the equivalent of a maximum of 0.5 g protein retained/min (6 mmol AA-N/min). This would provide sufficient AA for replenishment of peripheral (muscle) protein stores plus support of the placenta and fetus.     

Hepatic artery: effect of a meal in healthy persons and transplant recipients

Thirty healthy volunteers and 12 liver allograft recipients (two with cirrhotic changes seen at microscopy) were given a standard meal. Doppler sonography of the right and left hepatic arteries, the superior mesenteric artery, and the portal vein was performed. The change in hepatic arterial resistance was evaluated with the resistive index (RI). After the standard meal, portal venous flow increased in both the healthy volunteers and allograft recipients (more so in the latter group). Superior mesenteric arterial RI decreased in all subjects. A postprandial increase in hepatic arterial RI, likely reflecting constriction of the hepatic artery, was seen in both groups. It was absent in the two patients with recurrent transplant cirrhosis. These results show the importance of examining hepatic arterial flow in the fasting subject, since high resistance after a meal may be falsely interpreted as a sign of disease. Absence of a postprandial change in resistance of the hepatic artery could signal abnormal liver function.     

Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats

Tetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flow and the degree of portal-systemic shunting were measured after an overnight fast. The portal venous pressure and protal tributary blood flow were significantly decreased, while portal territory as well as hepto-collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, the the tetrandrine group. Mean arterial pressure, heart rate, portal-systemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long-term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemina in portal hypertensive rats without affecting the portal-systemic shunting.     

Angiokeratoma circumscriptum]

A case of superior mesenteric artery branch aneurysm is described. A 43-year-old female patient was hospitalized after the incidental discovery of a low echogenic mass next to the superior mesenteric artery trunk. A selective superior mesenteric arteriography confirmed aneurysms of the inferior pancreaticoduodenal artery and an aortogram demonstrated occlusion of the celiac trunk. Bypass between the abdominal aorta and the common hepatic artery and resection of aneurysms were performed. The possible etiology and operative procedure are discussed.     

Influence of corticotropin-releasing factor on pancreatic and islet blood flow in different regions of the rat pancreas

Corticotropin-releasing factor (CRF) has previously been shown to selectively dilate the mesenteric vascular bed, without affecting other vascular beds. Pancreatic blood flow and islet blood flow were therefore measured separately with a microsphere technique in the two regions of the rat pancreas perfused by the superior mesenteric artery (SMA) or celiac artery (CA) respectively. Intravenous infusion of CRF (0.25 microgram/kg b.w./min) caused an increase in both whole pancreatic blood flow and islet blood flow in the region of the pancreas perfused by the SMA. The fraction of whole pancreatic blood flow diverted through the islets in this part of the pancreas was, however, unaffected by CRF infusion (approximately 10%). CRF did not change either pancreatic or islet blood flow in the CA-perfused part of the pancreas, and did not affect the release of insulin.     

99mTc-MIBI used for diagnosis of portal hypertension: an experimental study

The authors investigated the relationship between portal-systemic shunting and portal pressure in 16 CCl4-induced cirrhotic wistar rats by 99mTc-MIBI photography of heart and liver. Based on radio-counts taken at 30 minutes after 99mTc-MIBI was given per rectum 8 rats or medial clonic vein 8 rats, heart radio-counts/liver radio-counts (H/L) and portal-systemic shunting index (SI) were recorded. It was shown that 1. H/L and SI of the two cirrhotic groups were greater than those of normals (P < 0.001); 2. H/L in cirrhotic rats by rectum 99mTc-MIBI administration was more closely related to free portal pressure (FPP, r = 0.83, P < 0.01) than in those by venous route (r = 0.74, P < 0.05) and its regressive formation FPP (kPa) = 0. 24 + 4.06 (H/L) was deduced and used to calculate portal pressure of cirrhotic rats. The very good relationship between the calculated and measured portal venous pressure was shown in a group of 12 cirrhotic rats (r = 0.85, P < 0.01). These findings suggested that the rectum administration of 99mTc-MIBI may be a useful method in calculating portal pressure and portal-systemic shunting in portal hypertensive patients.     

Doppler sonographic diagnosis of severe portal vein pulsatility in constrictive pericarditis: flow normalization after pericardiectomy

This case report describes the noninvasive assessment of hepatic and portal vein hemodynamics in a patient with constrictive pericarditis before and after pericardiectomy. Doppler sonography of the hepatic veins demonstrated a typical W-shaped pattern with pronounced late diastolic flow reversal that disappeared after surgery. Preoperatively, we observed severe pulsatility of the portal vein with flow reversal in systole; after pericardiectomy, portal venous flow was normal. We concluded that the high right atrial pressure in this patient might have led to increased hepatic venous outflow resistance, with subsequent trans-sinusoidal shunting between the hepatic artery and portal vein causing severe portal vein pulsatility. After pericardiectomy and a decrease in right atrial pressure, portal vein flow normalized.     

Sparing a replaced common hepatic artery during pancreaticoduodenectomy

A patient with a replaced common hepatic artery originating from the superior mesenteric artery successfully underwent a pylorus-sparing pancreaticoduodenectomy for chronic pancreatitis. This anomalous vessel was discovered by preoperative angiography but at operation the artery coursed ventral to the head of the pancreas, not, as one would predict, through the substance of the pancreas or dorsal to the pancreatic head and lateral to the portal vein. To our knowledge, this is the first case of a replaced common hepatic artery in this position reported in the English literature. Preservation of the entire blood supply to the liver and biliary tree is important to prevent biliary fistula after a Whipple procedure, and, in some cases, hepatic ischemia. In this case the artery was slightly larger and in the same position as the gastroduodenal artery, predisposing the patient to significant potential morbidity with a standard dissection.     

Significance of selective arteriographic patterns in the celiac axis and superior mesenteric artery in portal hypertension

Selective celiac and superior mesenteric arteriographies were performed in patients with portal hypertension. An arterioarterial (A-A) shunt between the superior mesenteric artery and the celiac axis via pancreatic arcades was found in fifteen of forty-three patients with associated massive splenomegaly. A mild A-A shunt disappeared after portacaval anastomosis alone, whereas a prominent A-A shunt was reduced but persisted. The persisting A-A shunt disappeared after splenectomy. These findings led us to suggest that the paucity of the blood flow in the common hepatic artery concomitant with increased splenic arterial flow to the massively enlarged spleen may result in a compensatory supply to the liver from the superior mesenteric artery via the shunt.     

The ratio of reduced glutathione/oxidized glutathione is maintained in the liver during short-term hepatic hypoxia

Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.     

Antioxidant status and dialysis: plasma and saliva antioxidant activity in patients with fluctuating urate levels

PURPOSE: The aim of this study was to clarify the clinical usefulness of combined CT during arterial portography (CTAP), and CT arteriography (CTA), for the diagnosis of hepatocellular carcinoma. MATERIALS AND METHODS: CTAP and CTA were performed in 58 patients with a combined 144 hepatocellular carcinoma (HCC) lesions. Arterial vascular access was obtained through bilateral punctures of the femoral artery with selective placement of catheters in the hepatic artery and superior mesenteric artery. CT scans were performed first during injection of contrast media into the superior mesenteric artery, followed by repeated imaging of the liver during injection of contrast media into the hepatic artery. Delayed CT (DCT) was also obtained 5 min after CTA. RESULTS: The detection rates for all 144 lesions were 73.6% with conventional contrast enhanced CT, 90.3% with CTAP, 95.8% with CTA, 87.5% with DCT, and 98.6% with combined CTAP and CTA. Of early HCC lesions (n = 18), 88.9%, 33.3%, 77.8%, 100%, and 88.9% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively. Of classical HCC lesions (n = 126), 71.4%, 98.4%, 98.4%, 85.7%, and 100% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively. CONCLUSION: Combining CTAP and CTA improved the radiologist's ability to detect lesions with confidence and to differentiate perfusion abnormalities of HCCs.     

Interaction versus independence of startle-modification processes in the rat

The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.     

Regional pharmacokinetics of 5-fluorouracil in dogs: role of the liver, gastrointestinal tract, and lungs

The purpose of this study was to determine the presence and extent of pulmonary elimination for 5-fluorouracil (FUra). A secondary aim was to characterize the relative importance of the liver, gastrointestinal tract, splanchnic region, and lungs toward the overall elimination of FUra. A total of 10 mixed-breed male and female dogs were used in these acute studies in which FUra was administered through a cephalic vein. Six dogs were studied at sequentially escalated dose rates of 0.125, 0.250, 0.500, 0.750, and 1.00 micromol/min/kg (8-fold range); four dogs were studied at sequentially escalated dose rates of 0.0625, 0.250, 0.750, 1.50, and 2.00 micromol/min/kg (32-fold range). Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (i.e., portal vein, carotid artery, hepatic vein, and pulmonary artery), perfusion rates were measured (hepatic artery, portal vein, and cardiac output), and pharmacokinetic parameters were directly assessed. Pulmonary elimination of FUra was conclusively demonstrated. Although only 17% of the drug was extracted by the lungs at the lowest dose rate, pulmonary clearance (16.0 ml/min/kg) was on the order of splanchnic clearance (13.5 ml/min/kg), or larger. As the dose rate increased, pulmonary clearance was more easily saturated than splanchnic clearance. Thus, it appears that at increasing dose rates, the splanchnic region becomes a more significant pathway, whereas the lungs have a reduced role in the overall elimination of FUra.