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Biomedical subjects

I S Benjamin

Publications and source records attributed to I S Benjamin.

At least 19 recordsLinked to original sources
PubMed1999

Localisation of hepatic vascular resistance sites in the isolated dual-perfused rat liver.

The locations of the vascular resistance sites which regulate vascular tone in the hepatic arterial and portal venous vasculatures of the rat liver were identified using a new, in vitro, dual-perfused liver preparation. Twelve livers of male Wistar rats were perfused via the hepatic artery and portal vein at fixed flow and at physiological pressure. Dose-related vasoconstriction to injections or infusions of noradrenaline was measured as transient or sustained increases in perfusion pressure, respectively, in the hepatic arterial and portal venous vasculatures. Direct injections/infusions of noradrenaline refer to those administered into the vasculature from which pressure was recorded, e.g., the effects of hepatic arterial (direct) injections/infusions of noradrenaline upon hepatic arterial perfusion pressure. Indirect injections/infusions of noradrenaline were those administered to the adjacent afferent vasculature, e.g., the effects of portal venous (indirect) injections of noradrenaline upon hepatic arterial perfusion pressure. The converse applies for recordings of portal venous perfusion pressure. The -log(M) ED50 values to direct (hepatic arterial) and indirect (portal venous) injections in the hepatic artery were 4.25+/-0.20 and 3.40+/-0.10, respectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (hepatic arterial) injections in the portal vein were 3.91+/-0.08 and 3.85+/-0.11, respectively, and were not significantly different (P > 0.05, Student's unpaired t-test). Similarly, the -log(M) ED50 values to direct (hepatic arterial) and indirect (portal venous) infusions in the hepatic artery were 5.28+/-0.11 and 3.75+/-0.12, respectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (hepatic arterial) infusions in the portal vein were 5.31+/-0.19 and 5.70+/-0.16, respectively, and were not significantly different (P > 0.05, Student's unpaired t-test). These results demonstrated that there is little transfer of noradrenaline from the portal venous to the hepatic arterial resistance sites, but significant transfer from the hepatic artery to the portal venous suggesting that; (a) the portal venous resistance sites are located at the sinusoidal or post-sinusoidal level; and (b) the hepatic arterial resistance sites are located at the pre-sinusoidal level.

Animals↗
PubMed1998

Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation.

The introduction of laparoscopic cholecystectomy has been associated with a rise in the number of reported bile duct injuries (0.3%-0.8%). Significant vascular injuries are rare (0.16%), but may lead to life-threatening complications. We present a case report of a patient undergoing transplantation for a laparoscopic cholecystectomy injury.

Adult↗
PubMed1998

Cholecystokinin receptors in human pancreatic cancer cell lines.

Recent studies have suggested that cholecystokinin (CCK) receptors may play a role in the development and growth of pancreatic cancers. We detected the expression of mRNA encoding CCK-A and CCK-B receptors in eight human pancreatic tumour cell lines using reverse transcription-polymerase chain reaction (RT-PCR), but not by RNase protection assays. The K-ras gene, which can be activated by G-coupled protein receptors such as CCK receptors, was mutated in codon 12 in five of the cell lines. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) phosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfected with human CCK-B receptor (NIH3T3CCK-BR) showed increased proliferation and phosphorylation to the peptides. Also, radioligand binding studies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia PaCa-2 cells, CCK receptors may not play a crucial role in supporting cell growth.

3T3 Cells↗
PubMed1998

The dependence of hepatic function upon sufficient oxygen supply during prolonged isolated rat liver perfusion.

It is unclear how the omission of a perfusate oxygen carrier may influence data derived from prolonged in vitro liver perfusions. The effects of reduced perfusate oxygen content upon liver function tests conducted in livers from male Sprague-Dawley rats perfused for 6 h, were studied using diluted rat blood (PCV = 10%) (group 1) and compared to lines perfused with Krebs' buffer (group 2). Perfusate and bile samples were withdrawn at the start and at hourly intervals following the commencement of perfusion for biochemical analysis of aspartate-serine transaminase, alkaline phosphatase, bilirubin, urea and potassium concentrations, and also for perfusate gas measurements for calculations of hepatic oxygen uptake. There were no significant differences between the initial perfusion pressures of 11.4+/-1.6 and 15.7+/-2.4 mm Hg at the start of perfusion (group 1 versus group 2, respectively). Maintenance of comparable perfusion pressures at the start of perfusion, however, resulted in a significant difference in the fixed flow rate between the two groups of 1.9+/-0.1 and 2.6+/-0.2* ml/min/g liver and resulted in significantly higher perfusion pressures in group 2 than in group 1 after 6 h of perfusion (18.2+/-2.0 versus 8.7+/-1.7 mmHg, respectively). Bile volume production was significantly greater in group 1 than in group 2, at 784+/-84 vs 458+/-75 microl/h** respectively. Hepatic oxygen uptake (HOU) was significantly greater in group 1 than in group 2, and maximal at 0.93+/-0.13 vs 0.32+/-0.08** micromol/min/g, respectively. Bile concentrations of bilirubin and potassium were significantly greater in group 1 than in group 2, 23.0+/-0.6 vs 4.9+/-0.4 micromol/l*** and 4.7+/-0.5 vs 1.1+/-0.2 mmol/l**, respectively. Perfusate concentrations of urea, bilirubin, and glucose were significantly higher in group 1 than group 2, 5.7+/-0.5 versus 1.4+/-0.2 micromol/l**; 2.4+/-0.5 versus 0.7+/-0.1 micromol/l** and 22.1+/-1.4 versus 17.8+/-0.9 micromol/l***. It is concluded that in vitro perfusion of the rat liver with Krebs'-Henseleit buffer (KHB) via the portal vein alone may be insufficient to maintain optimum liver function as assessed by the tests used. Inclusion of a perfusate oxygen carrier is optimal if livers are to be perfused at physiological pressures. *p < 0.05; **p < 0.01; ***p < 0.001; group 1 versus group 2, Student's unpaired t test.

Alkaline Phosphatase↗
PubMed1998

Differentiation between the effects of unprocessed portal blood and reduced liver function on brain indole amine metabolism in the portacaval shunted rat.

Changes in brain 5-HT turnover which have been associated with portal-systemic encephalopathy (PSE) in man were studied in rats with experimental PSE for intervals up to 15 weeks following the surgical construction of end-to-side portacaval shunts (PCS). These were compared to changes measured in portacaval transposed rats (PCT) which, show little hepatic dysfunction or cerebral abnormalities but, in common with the PCS rat, sustain total portal-systemic diversion. Thus any differences between these two groups were indicative of hepatic dysfunction and not the systemic diversion of portal blood. After 15 weeks, sustained increases were measured in brainstem and cerebral concentrations of the catabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), from 0.25+/-0.01 to 0.68+/-0.01*** microg g(-1) brain and from 0.18+/-0.01 to 0.31+/-0.03*** microg g(-1) brain respectively in PCS rats and were statistically greater to those measured in the brainstem and cerebrum of PCT and control rats. Sustained increases in cerebral concentrations alone of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, from 0.17+/-0.01 to 0.23+/-0.02 microg g(-1) brain were measured in PCS rats and were significantly*** greater than in PCT control rats after 15 weeks. Some early increases in 5-HTP were measured in PCS above control rats but these were not significant after 15 weeks. No sustained significant differences between the 3 groups were measured in 5-HT after 15 weeks. These data confirm previous evidence that the elevations in 5-HTP and 5-HIAA concentrations observed in experimental chronic liver failure and PSE are due to liver dysfunction and not portal-systemic diversion and may contribute additional information regarding the role of derangements in central 5-HT turnover as one of the causes of PSE. ***p<0.001, Newman-Keuls ANOVAR followed by Student's unpaired t-test for individual comparisons, (data shown are mean +/- SEM).

Animals↗
PubMed1998

The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver.

BACKGROUND: Portal hypertension is associated with gross haemodynamic disturbances characterised by high cardiac output, low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting. AIMS: To study the relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver. METHODS: Different sized microspheres were sequentially injected into the portal vein of male Wistar rats. RESULTS: Steady state portal venous pressure was increased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 microns diameter microspheres, respectively. Sequential injection of 15, 40, and 80 microns diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8 x 10(5) 80 microns microspheres consistently produced a steady state portal venous pressure of 19.0 (1.3) mm Hg but did not approach the much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observed during microsphere injections and further evidence for this was provided by the location of microspheres in the pulmonary vascular bed. The elevation in portal venous pressure achieved by microsphere injections was not significantly different to that produced in rats subjected to partial portal vein ligation (20.7 (0.5) mm Hg, p > 0.05). Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mm Hg following injection of 80 microns microspheres, suggesting a decrease in total hepatic blood flow. Conversely, injection of 15 microns microspheres induced an increase in wedged hepatic venous pressure from 7.0 (1.0) mm Hg to 12.4 (1.8) mm Hg, indicating a localised redistribution of blood flow at the presinusoidal level of the portal venous vascular network and increased intrahepatic shunt flow. CONCLUSION: It is suggested that there may be a protective pathophysiological role for these shunts when the liver is subjected to changes which induce acute portal hypertension.

Acute Disease↗
PubMed1997

The action of ATP on the hepatic arterial and portal venous vascular networks of the rabbit liver: the role of adenosine.

ATP is released from blood vessels during periods of hypoxia and may be responsible for hepatic arterial vasodilatation during instances of reduced hepatic portal venous flow. The role of adenosine in ATP-induced vasodilator and vasoconstrictor responses of the hepatic arterial and portal venous vascular networks respectively was studied in the isolated dual-perfused rabbit liver in vitro to ascertain whether ATP could be catabolised to adenosine during transit through the hepatic parenchyma. Intra-arterial and intra-portal injections of ATP (-10 to -4 log mol/100 g liver) resulted in dose-dependent vasodilatation in the hepatic artery and vasoconstriction in the portal vein. Addition of 8-phenyltheophylline (10 microM), a non-selective P1-purinoceptor antagonist, to the hepatic arterial and portal venous perfusate significantly inhibited the hepatic arterial ED50 for responses to intra-arterial injected ATP from -8.70 +/- 0.22 to -7.63 +/- 0.28 log mol/100 g liver (P < 0.001); it also inhibited hepatic arterial responses to, mid-range, portal venous injections of ATP. The data suggest that the hepatic arterial vasodliatation to ATP is partly mediated via catabolism to adenosine and may be an important mechanism during periods of relative hepatic hypoxia associated with portal flow reduction.

Adenosine↗
PubMed1997

Pharmacokinetics of valsartan in patients with liver disease.

OBJECTIVES: Valsartan (CGP 48933), an orally active angiotensin II antagonist, is eliminated mainly by hepatic clearance. To characterize the compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsartan. In addition, to determine the exposure to valsartan when liver function is impaired, a pharmacokinetic study (open, single dose) was performed in patients with mild and moderate impairment of liver function. PATIENTS: Biliary excretion of valsartan (after intravenous administration of 20 mg valsartan) was assessed in a patient who underwent a hepaticojejunostomy with subsequent bile drainage. Exposure to valsartan in patients with mild (n = 6) or moderate (n = 6) impaired liver function (Child's-Pugh classification) and matching (sex, age, and weight) healthy volunteers (n = 12) was studied after oral administration of a single dose of 160 mg valsartan. RESULTS: After intravenous administration, valsartan was eliminated mainly as unchanged drug in the bile. Mean exposure (measured as area under the plasma valsartan concentration-time curve) to valsartan was increased about twofold in both the mild and the moderate groups compared with matched (age, sex, and weight) healthy volunteers. CONCLUSION: These data are consistent with the pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.

Adult↗
PubMed1997

Biliary malignancies.

Biliary malignancies, including cancers of the intrahepatic and extrahepatic bile ducts, gallbladder and ampulla, should be considered in the differential diagnosis of patients with obstructive jaundice. Cancers of the intrahepatic bile ducts and ampulla are managed as liver and peri-ampullary tumours respectively. Extrahepatic bile duct cancers are diagnosed by cholangiography and evaluated for resectability by imaging and angiography. Vascular infiltration is the main contra-indication for resection, which may also involve the liver. Every attempt must be made to achieve curative resection, but local resection may be justified even if non-curative. Gallbladder cancers are usually advanced at the time of diagnosis and are unresectable--surgical palliation improves the quality of life by relieving biliary and gastric outlet obstruction. Long-term survival is possible after curative resection in early lesions that are usually diagnosed as an incidental finding after cholecystectomy for presumed gallstone disease. The role of adjuvant therapy in biliary malignancies needs further evaluation.

Bile Duct Neoplasms↗
PubMed1997

Cold-storage of rabbit thoracic aorta in University of Wisconsin solution reduces endothelium-independent vasodilation.

Optimum preservation conditions for storage of donor livers and blood vessels are essential for successful transplantation. The blood vessels are used as vascular conduits to facilitate anastomosis of the liver to the recipient's systemic vasculature. Failure of some transplants has been ascribed to thrombosis of these vascular conduits possibly because of alterations in vascular reactivity owing to inadequate storage techniques. To restrict data variability previously associated with studies using a heterogeneous sample of vessels from man, this study investigated changes in vascular reactivity in segments of rabbit thoracic aorta from male, age-matched, New Zealand White rabbits stored at 4 degrees C in either University of Wisconsin solution (UW; Du Pont Pharmaceuticals, UK) or Krebs-Bülbring buffer (KB). Percent vasodilation to acetylcholine remained significantly greater in UW than in KB at -log (M) concentrations of 7.0 (UW = 47.05 +/- 4.26 compared with KB = 13.20 +/- 7.20%; P < 0.001), 6.5 (UW = 66.82 +/- 4.83 compared with KB = 26.60 +/- 9.48%; P < 0.01), and 6.0 (UW = 83.68 +/- 5.26 compared with KB = 31.20 +/- 9.83%; P < 0.001). This was not significantly different to relaxation in unstored arteries and suggested improved endothelial function and structure, confirmed by electron microscopy. Percent vasodilation to sodium nitroprusside was significantly lower in UW than in unstored (D0) arteries at -log (M) concentrations of 7.5 (D0 = 28.27 +/- 4.02 compared with UW = 15.21 +/- 1.82%; P < 0.01), 7.3 (D0 = 52.58 +/- 5.05 compared with UW = 29.23 +/- 1.94%; P < 0.01), 7.0 (D0 = 69.70 +/- 4.85 compared with UW = 49.72 +/- 2.49%; P < 0.05), and 6.4 (D0 = 93.16 +/- 2.93 compared with UW = 71.29 +/- 5.20%; P < 0.05). Percent vasodilation was also lower in UW- compared with KB-stored arteries at -log (M) sodium nitroprusside concentrations of 7.0 (UW = 49.72 +/- 2.49 compared with KB = 64.11 +/- 5.03%; P < 0.05) and 6.4 (UW = 71.29 +/- 5.20 compared with KB = 96.91 +/- 5.96; P < 0.05). Electron microscopy confirmed that this was not a result of degradation of smooth muscle structure. The nitric oxide synthase inhibitor L-NG-nitro-L-arginine methyl ester (100 microM) did not significantly modulate sodium nitroprusside-induced vasodilation in unstored arteries, when endothelial function was maximum, or in UW-stored arteries, suggesting that the reduced responses in UW-stored arteries were not because of increased synthesis of nitric oxide. This reduced relaxation to sodium nitroprusside was therefore nitric oxide-independent and not a result of competition between sodium nitroprusside and endothelial 'nitric oxide donation' for cGMP. In summary, cold-storage preservation with UW reduced endothelium-independent vascular relaxation by mechanisms other than competition with NO; this requires further evaluation.

Acetylcholine↗
PubMed1996

External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability.

BACKGROUND AND PURPOSE: Cholangiocarcinoma is rare but carries a poor prognosis. Radiotherapy has been used either as an adjuvant treatment following surgical resection of tumour or for palliation. The purpose of this study was to assess the feasibility and morbidity of accelerated external beam radiotherapy with or without intraluminal radiotherapy in the treatment of locally advanced bile duct cancer. MATERIALS AND METHODS: Thirty eight patients were treated. Surgical procedures performed prior to radiotherapy were extended hepatectomy (3), hepaticojejunostomy with tumour resection (6), palliative biliary-enteric bypass (6), biopsy (4), Whipple's procedure (1), gastrojejunostomy (1) and cholecystectomy (1). Twenty patients received external beam radiotherapy (ERT). Six patients received one Phase of ERT and 12 received two Phases, separated by a 2-week gap. Dose per Phase was 22.5 Gy in 10 twice daily fractions. After 1989, dose per Phase was increased to 27.5 Gy. One patient received Phase I ERT (30.0 Gy) using conventional fractionation and one patient received an uninterrupted, conventionally fractionate course of treatment (50.0 Gy). Fourteen patients received both ERT and intraluminal radiotherapy (IRT) using iridium-192 (192Ir) wire passed through a percutaneous, transhepatic catheter (median dose, ERT 23.8 Gy + IRT 40.0 Gy). In addition, four patients received IRT alone (median dose 45.0 Gy at 1 cm radius). Patients were followed for at least 42 months. RESULTS: Median overall survival was 15 months. Overall survival for the whole group at 1,2 and 3 years was 59.6%, 32.5% and 16.2%. Thirty four patients died of disease. Radiotherapy caused acute toxicity in seven patients. According to RTOG/EORTC criteria toxicity was Grade 1 in four cases, Grade 2 in two cases and Grade 3 in one case. Two patients developed gastrointestinal bleeding as a late complication of radiotherapy. CONCLUSIONS: Accelerated external beam radiotherapy with or without intraluminal radiotherapy is feasible and associated with acceptable toxicity when used in the management of advance cholangiocarcinoma.

Bile Duct Neoplasms↗
PubMed1995

Postcholecystectomy bile duct strictures. Management and outcome in 130 patients.

OBJECTIVE: To evaluate management strategies for the treatment of patients with postcholecystectomy bile duct strictures. DESIGN: Retrospective study. SETTING: The Hepatobiliary Unit of Hammersmith Hospital, London, England. PATIENTS: One hundred thirty consecutive patients referred for treatment of postcholecystectomy bile duct strictures. The majority (80 patients [61.5%]) had undergone multiple operative procedures before referral, and 81 (62.3%) had undergone at least one previous stricture repair. At referral, more than half of the patients had a stricture involving the confluence of the bile ducts (n = 78 [60%]), and 23 (17.7%) had evidence of portal hypertension. MAIN OUTCOME MEASURES: Perioperative mortality, stricture recurrence, and long-term outcome. RESULTS: One hundred twenty-two patients (94%) underwent operative treatment: 110, stricture repair alone; four, portosystemic shunt and stricture repair; and eight, miscellaneous operative procedures. Among the 110 patients treated by stricture repair alone, there was an operative mortality rate of 1.8% (n = 2), and 79 patients (76%) had a good result, with no biliary symptoms and no need for intervention during mean follow-up of 7.2 years (range, 1 to 13 years). Twenty-two patients (21%) required either radiological intervention or operative revision of the biliary-enteric anastomosis, but 11 (50%) of these patients subsequently did well and had no biliary symptoms. Thus, 90 patients (87%) had a good or excellent long-term result after initial or follow-up treatment. There were no deaths among the 108 patients who underwent stricture repair alone by direct suture techniques. Factors influencing mortality included hypoalbuminemia, an elevated serum bilirubin level, and the presence of liver disease and portal hypertension. Preoperative factors influencing failure of the stricture repair in long-term follow-up included discontinuity of the right and left ducts at the time of stricture repair (Bismuth grade 4) and three or more previous attempts at operative repair before referral to our center. CONCLUSIONS: Operative repair of bile duct strictures using direct sutured techniques remains the procedure with which alternative methods will need to be compared, with close attention to long-term outcome.

Adult↗
PubMed1995

Changes in E-cadherin immunoreactivity in the adenoma-carcinoma sequence of the large bowel.

We have used an avidin-biotin immunoperoxidase technique to localise epithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, in 107 paraffin-embedded sections from 93 patients consisting of 24 with colorectal adenoma, 55 with rectal carcinoma and 14 with liver metastases. The corresponding primary colorectal tumours were also studied in these cases. E-cadherin was expressed by normal colorectal epithelial cells with typical membranous staining at the intercellular junctions. Loss of normal membranous E-cadherin expression and presence of cytoplasmic staining were found frequently in adenomas larger than 1 cm (P < 0.01), with high grade dysplasia and villous histology (P < 0.01). In primary rectal cancers, loss of membranous expression correlated with high tumour grade. No correlation was seen with Dukes and Jass stage, local extramural spread and 5-year recurrence rate. Complete loss of membranous E-cadherin immunoreactivity was seen in 7/14 (50%) liver metastases in which 6/7 (86%) showed intense membranous E-cadherin immunoreactivity in the corresponding primary tumour. Our data indicate that changes in E-cadherin immunoreactivity and cellular localisation correlate with size, severe dysplasia in adenomas and tumour grade in carcinomas. However, there seems to be no correlation between loss of membranous E-cadherin immunoreactivity and the invasive and metastatic potential of the carcinomas.

Adenoma↗
PubMed1995

Hepatic function during prolonged isolated rat liver perfusion using a new miniaturized perfusion circuit.

Previous designs of isolated rat liver perfusion circuits used for toxicological investigations are often expensive, cumbersome, or traumatic in relation to hepatic biocompatibility following extended perfusion times. A new, miniaturized circuit that incorporates a novel design of organ bath, to maintain a buoyant preparation, and a high-efficiency miniaturized membrane tubing oxygenator is described. Livers from male Sprague-Dawley rats were perfused continuously for 6 hr in vitro using rat blood diluted to a perfusate hematocrit of 9.75 +/- 0.35% with Krebs-Henseleit buffer (KHB). Hepatic function was evaluated by measurement of perfusion pressure, flow rate, bile volume production, bile bilirubin content, hepatic oxygen uptake (HOU), bromosulphthalein (BSP) removal, hepatic enzyme activities, and electrolyte concentrations, and finally by histological examination. Perfusion pressure and flow rate remained stable at 8.7 +/- 1.7 mmHg and 1.92 +/- 0.06 mL min-1 g-1 liver, respectively. Bile volume production and HOU were maximal at 784 +/- 84 microL h-1 and 0.99 micromol/L min-1 g-1 respectively. Erythrocyte damage in the perfusate was evaluated by measurement of reduction in perfusate hematocrit from 9.75 +/- 0.35% to 9.27 +/- 0.24%, and increases in plasma free hemoglobin, which rose from 85.8 +/- 12.3 mg% to 650.1 +/- 53.3 mg% over the 6-hr perfusion period studied. Using bile volume production, hepatic oxygen uptake, and the liberation of plasma free hemoglobin as the most sensitive indices of adverse conditions, the new circuit was capable of supporting an isolated perfused rat liver for periods of up to 6 hr under close-to-physiological conditions.

Animals↗
PubMed1995

Pancreatic carcinoma.

The management of patients with pancreatic carcinoma poses many problems. The diagnosis is usually made late, generally because the patients present late, but it is not unusual to find patients who have had many negative investigations for vague upper abdominal symptoms only to be diagnosed as having pancreatic carcinoma many months later. Staging the disease is equally difficult and often inaccurate. The results of treatment are to date discouraging even in those patients diagnosed early. But the outlook is not totally dismal; in recent years the results for surgical resection of pancreatic lesions have improved; adjuvant treatment may finally be having an effect, although small, on this relentless disease. The most notable inroad made in the management of pancreatic cancer in the last 10 years is the improvement in palliation due to the use of the endoprosthesis. In spite of the poor results we must continue to search actively for more accurate methods of diagnosis and better methods of treatment.

Antigens, Neoplasm↗
PubMed1995

The transhepatic response to noradrenaline in the rabbit liver: the influence of arterioportal pressure gradient.

The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10(-10)-10(-4) mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline. At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68.5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged. These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance.

Animals↗