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Biomedical subjects

J N Baxter

Publications and source records attributed to J N Baxter.

At least 109 records · Page 6Linked to original sources

Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in the rat.

The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man.

Acute Disease↗

Effects of a selective beta 2-blocker (ICI 118,551) on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat.

The effects of a selective beta 2-blocker (ICI 118,551) on hepatic haemodynamics were studied in cirrhotic and non-cirrhotic rats. Infusions of 10 and 20 microgram (kg body wt)-1 min-1 beta 2-blocker (in cirrhotic and non-cirrhotic rats) significantly reduced portal pressure, portal venous flow and liver blood flow without altering heart rate. Splanchnic vascular resistance was significantly increased following infusions of 10 and 20 micrograms (kg body wt)-1 min-1 beta 2-blocker. An intraportal injection of beta 2-blocker (10 micrograms body wt)-1 or hepatic artery ligation lowered portal pressure by approximately the same magnitude. Intraportal injection of beta 2-blocker after hepatic artery ligation did not further reduce portal pressure. The results indicate that a selective beta 2-blocker reduces portal pressure by a combination of increased splanchnic vascular resistance and hepatic arterial resistance. It is concluded that a selective beta 2-blocker may be of clinical value in the long-term managements of portal hypertension.

Adrenergic beta-Antagonists↗

The effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the cirrhotic rat.

The effects of a somatostatin analogue, SMS 201-995 on hepatic haemodynamics were studied in rats with dimethylnitrosamine-induced cirrhosis. An intravenous infusion of 1, 2 or 4 micrograms kg-1 body wt h-1 SMS 201-995 produced a rapid and sustained decrease in portal pressure, portal venous flow and liver blood flow without significantly altering arterial blood pressure or pulse. The reductions in portal pressure, portal venous flow and liver blood were accompanied by an increase in splanchnic vascular resistance. Portal venous resistance was not affected. Subcutaneous injection of 2 micrograms kg-1 body wt SMS 201-995 produced a gradual decrease in portal pressure, the maximum reduction occurring 18 min after administration. This reduction in portal pressure was sustained for a further 20 min. The results suggest that SMS 201-995 may be of value in the control of bleeding oesophageal varices. Furthermore, the prolonged duration of action of SMS 201-995 following its subcutaneous administration suggests that the analogue may be useful in the long-term management of portal hypertension in patients with cirrhosis.

Animals↗

Effects of a somatostatin analogue (SMS 201-995) on hepatic and splenic reticulo-endothelial function in the rat.

The effects of a long acting somatostatin analogue, SMS 201-995, on reticulo-endothelial system (RES) activity were studied in rats. Administration of 2 micrograms SMS 201-995 subcutaneously twice a day for 7 days significantly increased the splenic and hepatic uptake of 99mTc-sulphur colloid and damaged 51mCr-red blood cells. Furthermore, SMS 201-995 administration significantly increased the plasma clearance of colloidal carbon as indicated by a lower area under the curve and an increased elimination constant. SMS 201-995 administration also significantly improved survival after intraperitoneal injection of Escherichia coli endotoxin. These results suggest that SMS 201-995 stimulates RES activity in rats. It is suggested that SMS 201-995 may be of value in stimulating RES activity in patients with cirrhosis and portal hypertension.

Animals↗

Effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the pig and on intravariceal pressure in man.

The effects of a somatostatin analogue, SMS 201-995, on hepatic haemodynamics in the pig and on intravariceal pressure in man were studied. An infusion of 250 micrograms/h SMS 201-995 significantly reduced portal pressure, portal venous flow and hepatic artery flow in the pig. These changes in hepatic haemodynamics were accompanied by a reduction in cardiac output, a reflex slowing of the heart and an increase in arterial blood pressure. Splanchnic vascular resistance was increased following SMS 201-995 administration but hepatic vascular resistance remained unchanged. Administration of 50 micrograms SMS 201-995 reduced the intravariceal pressure from 27.4 +/- 2.5 to 15.8 +/- 2.1 mmHg in 9 patients with cirrhosis and portal hypertension. Administration of 50 micrograms SMS 201-995 also reduced portal pressure from 29 to 22 mmHg in a patient undergoing an elective portacaval shunt. These results suggest that SMS 201-995 may be of value in the control of bleeding oesophageal varices. Furthermore, because of its prolonged duration of action SMS 201-995 may be useful in the long term management of portal hypertension in patients with cirrhosis.

Animals↗

The effects of vasopressin on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat.

Liver blood flow (xenon-133 clearance method) and portal venous flow were measured in cirrhotic and non cirrhotic rats following the infusion of vasopressin at varying rates. At low rates of infusion, vasopressin had no significant effect on portal venous flow or liver blood flow in cirrhotic or non-cirrhotic rats. Infusion of vasopressin at a rate of 0.08 microU/g body wt/min in non-cirrhotic rats and 0.04 and 0.08 microU/g body wt/min in cirrhotic rats decreased portal venous flow and increased liver blood flow. At higher rates of infusion (0.2 microU/g body wt/min in non-cirrhotic rats and 0.16 microU/g body wt/min in cirrhotic rats) these effects were reversed. Furthermore, an infusion of 0.08 microU/g body wt/min vasopressin significantly reduced portal pressure in the cirrhotic rat. However, portal pressure was not significantly altered following an infusion of 0.16 microU/g body wt vasopressin. The implications of these findings in relation to the possible deleterious effects of high rates of vasopressin infusion in the management of portal hypertension and bleeding oesophageal varices is discussed.

Animals↗

A dimethylnitrosamine-induced model of cirrhosis and portal hypertension in the rat.

A method of producing cirrhosis consistently in rats by the administration of dimethylnitrosamine (DMNA) is described. Two weeks following the cessation of DMNA treatment there was distortion of the lobular architecture of the liver and some focal nodule formation. This 'pre-cirrhotic' state was accompanied by portal hypertension, biochemical abnormalities and the development of ascites. The mortality 2 weeks after cessation of DMNA was 42%. Twenty-four weeks after DMNA treatment cirrhosis had developed with diffuse nodularity and fibrosis, marked portal hypertension, and accumulation of ascites. There was also a deterioration in liver function, with hypoproteinaemia and jaundice. The overall mortality 24 weeks after the cessation of DMNA treatment had risen to 52%. This model of cirrhosis in the rat may be useful in evaluating the efficacy of drugs in the long-term management of portal hypertension in man.

Animals↗

The clearance of Xenon-133 following its parenchymal injection: a rapid method for estimating functional liver blood-flow.

Portal venous flow, total hepatic blood-flow and hepatic artery flow were measured in healthy dogs by electromagnetic flowmetry and a double indicator dilution technique. Functional liver blood-flow was measured by the double indicator dilution technique. Functional hepatic blood-flow did not correlate with portal venous flow, total hepatic blood-flow or hepatic artery flow, measured by either electromagnetic flowmetry or a double indicator dilution technique. There was a good correlation (r = 0.83, P less than 0.001) between functional hepatic blood-flow and liver blood-flow, measured by the clearance of Xenon-133 injected directly into the liver parenchyma. It is concluded that the clearance of Xenon-133, injected directly into the liver parenchyma, is a rapid and simple method for measuring functional hepatic blood-flow.

Animals↗

Relationship between gastric emptying of solids and gall bladder emptying in normal subjects.

Very little is known about the normal temporal and quantitative relationships between gastric emptying and gall bladder emptying. Using a non-invasive double isotope technique these relationships were investigated in 22 normal healthy adults. 99Tcm EHIDA was used as the biliary tracer and 113Inm labelled bran as the gastric content tracer. Gastric emptying was monoexponential with a t1/2 of 45 +/- 3 minutes (mean +/- SEM). In 15 subjects the gall bladder emptied in relation to eating according to a double exponential function. In these subjects 15.0 +/- 1.6% of gall bladder contents emptied before gastric emptying began. They could be further divided into two clear cut types (p less than 0.001), according to the ejection fraction at 10 minutes and the t1/2 of the first exponential. Emptying of the gall bladder was faster and more of its contents were ejected in subjects with a type I response (n = 9) than in subjects with a type II response (n = 6). In the remaining seven subjects the gall bladder began to empty spontaneously, unrelated to eating. These observations suggest that gall bladder emptying: (a) may have a cephalic phase, (b) can be expressed as a double exponential function, (c) may occur unrelated to eating, (d) which occurs only in relation to eating would appear to be either fast (type I) or slow (type II).

Adult↗

Isolated liver perfusion: the choice of anaesthetic.

Perfused livers isolated from rats under halothane anaesthesia produced greater amounts of bile, released smaller amounts of aspartate aminotransferase, and had a much greater ability to maintain a constant concentration of glucose in perfusates than those obtained with ether or pentobarbitone. Little or no effect was shown on the ability of the liver to synthesize urea and to retain potassium within the organ. It appears, therefore,that halothane is the anaesthetic of choice when removing the liver from the laboratory rat.

Anesthesia↗

Circulating levels of arginine vasopressin before and during the infusion of the hormone in patients presenting with bleeding oesophageal varices.

Circulating levels of antidiuretic hormone (ADH) were measured in patients presenting with bleeding oesophageal varices before and during treatment with arginine vasopressin. There was no significant difference in the circulating levels of ADH before and during treatment with arginine vasopressin in patients in which the hormone successfully controlled haemorrhage and those in which it did not. It is concluded that the failure of vasopressin to control variceal haemorrhage in approximately 40% of patients presenting for treatment cannot be attributed to higher circulating levels of the hormone in these subjects.

Arginine Vasopressin↗

Gall-bladder emptying.

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Biliary Dyskinesia↗