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Irving S Benjamin

Publications and source records attributed to Irving S Benjamin.

12 recordsLinked to original sources
PubMed2005

Risk-adjustment in hepatobiliary pancreatic surgery.

AIM: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients. METHODS: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality. RESULTS: The operative mortality in the series was 3.95%. This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Post-operative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117) or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery. CONCLUSION: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.

Adult↗
PubMed2005

Expression of Ras GTPase isoforms in normal and diseased pancreas.

BACKGROUND: Ki-Ras is well studied in its oncogenic form in relation to pancreatic pathologies. However, the individual contribution of each of the wild-type Ras isoforms (Ha-, Ki-, and N-) in pancreatic cells in health and disease is unknown. METHODS: Archival formalin-fixed, paraffin-embedded specimens of normal (n = 6) and malignant pancreas (n = 35) were used for immuno-histochemical detection of Ras isoforms using a modified polymer system. In addition, immunogold labelling for Ras isoforms was done for subcellular localisation under electron microscopy. RESULTS: Pancreatic ductal cells expressed Ha-Ras in the cytoplasm, with Ki-Ras in the apical region and N-Ras (50% of cases) in a supranuclear distribution. Pancreatic acinar cells express all three isoforms with some nuclear expression of Ki-Ras and supranuclear expression of N-Ras. Islets show Ki- and Ha-Ras mainly with differential expression of Ha-Ras (beta cells showing less Ha-Ras and more Ki-Ras than alpha cells). Electron microscopy shows that Ha-Ras is mainly localised in the endoplasmic reticulum and Golgi apparatus of the acinar cells with some plasma membrane localisation of Ki-Ras in the ductal cells. There was no change in any of the Ras isoform expression in the ductal or acinar cells in various malignancies studied (Mann-Whitney U test, p > 0.1). CONCLUSIONS: Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state. Understanding this distinct functional distribution patterns in detail is an essential step if mutant Ki-Ras is to be targeted in the pancreas by genetic or molecular therapeutic tools.

Genes, ras↗
PubMed2005

Hepato-cardiovascular response and its regulation.

AIM: To determine the possible existence of a hepato-cardiovascular response and its regulatory mechanism in normal rats. METHODS: Systemic hemodynamic changes following intraportal injection of latex microspheres were studied in two modified rat models of hepatic circulation, in which the extrahepatic splanchnic circulation was excluded by evisceration and the liver was perfused by systemic blood via either the portal vein (model 1) or hepatic artery (model 2) in vivo. RESULTS: In model 1, intraportal injection of two sized microspheres (15-mum and 80-mum) induced a similar decrease in mean arterial pressure, while extrahepatic portal venous occlusion induced an immediate increase in mean arterial pressure. In model 2, microsphere injection again induced a significant reduction in mean arterial pressure, aortic blood flow and aortic resistance. There were no significant differences in these parameters between liver-innervated rats and liver-denervated rats. The degrees of microsphere-induced reduction in mean arterial pressure (-38.1+/-1.9% in liver-innervated rats and -35.4+/-2.1% in liver-denervated rats, respectively) were similar to those obtained by withdrawal of 2.0 mL of blood via the jugular vein (-33.3+/-2.1%) (P>0.05). Injection of 2.0 mL Haemaccel in microsphere-treated rats, to compensate for the reduced effective circulating blood volume, led to a hyperdynamic state which, as compared with basal values and unlike control rats, was characterised by increased aortic blood flow (+21.6+/-3.3%), decreased aortic resistance (-38.1+/-3.5%) and reduced mean arterial pressure (-9.7+/-2.8%). CONCLUSION: A hepato-cardiovascular response exists in normal rats. It acts through a humoral mechanism leading to systemic vasodilatation, and may be involved in the hemodynamic disturbances associated with acute and chronic liver diseases.

Animals↗
PubMed2003

The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo.

BACKGROUND: The role of adenosine and ATP in the regulation of hepatic arterial blood flow in the "buffer response" was studied in vitro and in a new in vivo model in the rabbit. The model achieves portal-systemic diversion by insertion of a silicone rubber prosthesis between the portal vein and inferior vena cava and avoids alterations in systemic haemodynamics. RESULTS: Hepatic arterial (HA) blood flow increased in response to reduced portal venous (PV) blood flow, the "buffer response", from 19.4 (3.3) ml min-1 100 g-1 to 25.6 (4.3) ml min-1 100 g-1 (mean (SE), p < 0.05, Student's paired t-test). This represented a buffering capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1 micrograms kg-1-0.5 mg kg-1) elicited immediate increases in HA blood flow to give -log ED50 values of 2.0 and 1.7 mg kg-1 for ATP and adenosine respectively. Injection of ATP and adenosine had no measurable effect on PV flow. In vitro, using an isolated dual-perfused rabbit liver preparation, the addition of 8-phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly inhibited the HA response to intra-arterial adenosine and to mid-range doses of intra-portal or intra-arterial ATP (p < 0.001). CONCLUSIONS: It is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P1-purinoceptors following catabolism of ATP to adenosine.

Journal Article↗
PubMed2003

The role of nitric oxide in systemic and hepatic haemodynamics in the rat in vivo.

The physiological role of nitric oxide (NO) in portal venous and hepatic arterial haemodynamics in the rat in vivo during healthy and diseased conditions remains unclear. The present study determined the physiological role of nitric oxide in hepatic haemodynamics in the rat in vivo during healthy conditions as a basis for future pharmacological work. Male Wistar rats (300-350 g) were anaesthetised with fentany/fluanisone (0.3 mg/kg s.c.) and midazolam (0.3 mg/kg s.c.) and heparinised (30 U/100 g i.v.) via a cannulated left carotid artery for measurement of heart rate, mean arterial pressure, and the difference between systolic and diastolic blood pressures (P(S-D)). Following laparotomy, two distal ileocolic veins were cannulated, one catheter introduced to a distance of 1 cm and used for intraportal drug injections and the other to the main trunk of the portal vein for continuous measurement of portal venous pressure. The portal venous trunk and hepatic artery were carefully isolated and electromagnetic probes placed around each of them for measurement of portal venous flow and hepatic arterial flow. Augmentation of NO production was achieved by intraportal injection of 0.2, 0.4, 0.6 and 0.8 g/kg L-arginine and the NO donor, 3-morpholinosydnonimine (SIN-1), was injected intraportally at 0.2, 0.4, 0.6 and 0.8 mg/kg. L-NAME, the non-selective NOS inhibitor, was injected intraportally in increasing doses of 5, 10, 15 and 20 mg/kg in the absence or presence of L-arginine in doses of 0.2 and 0.5 g/kg. L-arginine increased portal blood flow by 25% without significant changes in systemic haemodynamics. SIN-1 decreased mean arterial pressure by 33% with no effect on portal blood flow. Both L-arginine and SIN-1 reduced portal venous pressure by 25% in a dose-dependent manner. L-NAME had no effect on portal haemodynamics despite a significant increase in systemic arterial pressure of 60% that was reduced dose-dependently by L-arginine. Hepatic arterial flow increased by 88% and 49% at the second and third doses of L-arginine and by 68% and 27% at the first two doses of L-NAME. No significant changes in hepatic arterial flow were found when L-NAME and L-arginine were given together. It is concluded that augmented endogenous NO production increased portal flow. Inhibition of endogenous NO had no effect on portal haemodynamics. Endogenous NO may not play a major role in regulation of portal haemodynamics in the rat in vivo.

Animals↗
PubMed2003

Mortality control charts for comparing performance of surgical units: validation study using hospital mortality data.

OBJECTIVE: To design and validate a statistical method for evaluating the performance of surgical units that adjusts for case volume and case mix. DESIGN: Validation study using routinely collected data on in-hospital mortality. DATA SOURCES: Two UK databases, the ASCOT prospective database and the risk scoring collaborative (RISC) database, covering 1042 patients undergoing surgery in 29 hospitals for gastro-oesophageal cancer between 1995 and 2000. STATISTICAL ANALYSIS: A two level hierarchical logistic regression model was used to adjust each unit's operative mortality for case mix. Crude or adjusted operative mortality was plotted on mortality control charts (a graphical representation of surgical performance) as a function of number of operations. Control limits defined as 90%, 95%, and 99% confidence intervals identified units whose performance diverged significantly from the mean. RESULTS: The mean in-hospital mortality was 12% (range 0% to 50%). The case volume of the units ranged from one to 55 cases a year. When crude figures were plotted on the mortality control chart, four units lay outside the 90% control limit, including two outside the 95% limit. When operative mortality was adjusted for risk, three units lay outside the 90% limit and one outside the 95% limit. The model fitted the data well and had adequate discrimination (area under the receiver operating characteristics curve 0.78). CONCLUSIONS: The mortality control chart is an accurate, risk adjusted means of identifying units whose surgical performance, in terms of operative mortality, diverges significantly from the population mean. It gives an early warning of divergent performance. It could be adapted to monitor performance across various specialties.

Hospital Mortality↗
PubMed2003

The action of nitric oxide on hepatic haemodynamics during secondary biliary cirrhosis in the rat.

The role of nitric oxide (NO) in portal hypertension is poorly understood. The role of NO upon hepatic arterial and portal venous vasoconstrictor responses to noradrenaline and ATP in rats with secondary biliary cirrhosis was evaluated. Cirrhosis was induced by bile duct ligation after which livers were excised and dual-perfused in vitro. Concentration-dependent dose-response curves were then constructed to hepatic arterial and portal venous noradrenaline and ATP. Hepatic arterial responses to noradrenaline and ATP were significantly attenuated in cirrhotic rats. 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME) restored attenuated hepatic arterial responses to noradrenaline and ATP in cirrhotic rats. Portal venous responses to noradrenaline in cirrhotic rats were significantly increased compared to controls and were not affected by L-NAME. However, portal venous responses to ATP were significantly attenuated in cirrhotic rats and were also not restored by L-NAME. Hepatic arterial or portal venous responses to noradrenaline did not change after infusion of L-NAME. Hepatic arterial responses to noradrenaline and ATP were significantly attenuated in cirrhotic rats, possibly due to increased production of NO. However, portal venous responses in cirrhotic rats were increased to noradrenaline and attenuated to ATP, and were not related to increased NO production.

Adenosine Triphosphate↗
PubMed2003

Biliary cystic disease: the risk of cancer.

Congenital choledochal cysts carry a risk of cancer, probably as a result of a sequence of pancreatobiliary reflux, inflammation, dysplasia with or without intestinal metaplasia, and invasive carcinoma. A combination of biliary stasis due to poor drainage of a stagnant pool of bile and increased mutagenicity of the bile acids may be ultimately responsible. There is very frequently an anomalous pancreato-biliary ductal junction, and the reflux of pancreatic juice into the bile duct is thought to play a central role in the process of carcinogenesis. The risk of cancer is low in childhood (under 1% in the first decade), but shows a clear increase with age (over 10% in the third decade). The implication for management is that total excision of the extrahepatic biliary tree at risk remains the gold standard for management of these cysts, and simple bypass in infancy or childhood leaves the risk of cancer, though possibly diminished, still significant.

Adenocarcinoma↗
PubMed2002

Cold storage of rabbit thoracic aorta in University of Wisconsin solution attenuates P2Y(2) purine receptors.

Post-transplantation thrombosis may occur in donor segments of iliac arteries and livers following surgical removal and storage in University of Wisconsin (UW) solution for transplantation. We have previously suggested that purine receptors are vulnerable to denaturation after UW storage. The aims of the present study were to determine what particular subtypes of purine P2Y receptors in rabbit thoracic aorta deteriorate after 8 days of UW storage by studying vascular reactivity to acetylcholine, ATP, 2MeSATP and UTP. Ring segments of aortae from male New Zealand White rabbits were mounted upon fine-wire myographs and vasodilatation to the above agents tested on fresh tissue, and after 8 days of UW storage. Vasodilatation to ATP was attenuated by 100 microM L-NAME in fresh tissue suggesting that the relaxant response was, in part, due to nitric oxide (NO). P2Y-mediated relaxation to ATP was significantly attenuated by UW storage and cholinergic responses were not. This attenuated relaxation to ATP was not further attenuated by L-NAME, suggesting a loss of the NO-dependent mechanism. De-endothelialisation indicated that UTP-mediated vasorelaxation, via P2Y(2) receptors, was endothelium-dependent. Any residual endothelium-independent relaxation to UTP was abolished by UW storage and endothelium-dependent UTP relaxation was reduced to the same level as that seen in fresh, de-endothelialised tissue. In contrast responses to 2MeSATP, via P2Y(1) receptors, were predominantly endothelium-independent and were only partially attenuated by UW storage. Responses to pyridoxalphosphate-6-azophenyl-2('),4(')-disulphonic acid (PPADS) and L-NAME suggested that vasorelaxation to 2MeSATP and UTP was mediated by P2Y(1) and P2Y(2) receptors, respectively. It is therefore concluded that UW storage predominantly decreases P2Y(2) receptor-mediated vascular reactivity.

Acetylcholine↗
PubMed2002

Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality.

BACKGROUND/AIMS: Hepatotoxin-induced rat models of liver cirrhosis are limited by the wide heterogeneity of cirrhosis produced. The present study developed a modified, reliable, and reproducible technique by which hepatic and systemic responses to thioacetamide during induction of cirrhosis were monitored by weekly weight changes. METHODS: Male Wistar rats (200-230 g) were divided into three groups. Group 1 (n=20) received continuous administration of 0.03% (w/v) thioacetamide in the drinking water for 12 weeks. Group 2 (n=20) received the same concentration of 0.03% thioacetamide as an initial concentration that was modified according to weekly weight changes in response to thioacetamide during the induction of cirrhosis. Group 3 (n=6) received normal water and served as controls. RESULTS: Mortality of Group 1 was 30% and the production of cirrhosis was only 45%. In contrast, there were no deaths in Group 2 and well-developed macronodular cirrhosis was found in 90% of the rats which was associated with significant portal hypertension, as indicated by increased portal venous pressure (13.6+/-0.4 vs. 9.1+/-0.3 mmHg, cirrhotic vs. control, respectively, P<0.01, Student's unpaired t-test). CONCLUSIONS: Variations in responses to thioacetamide can be easily monitored by weekly weight changes to reduce mortality to zero and simultaneously increase the production and quality of cirrhosis induced in rats.

Animals↗