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Biomedical subjects

R Shields

Publications and source records attributed to R Shields.

At least 55 records · Page 3Linked to original sources
PubMed1987

SMS 201-995 and variceal haemorrhage.

Sandostatin (SMS 201-995) was evaluated in the treatment of variceal bleeding in 9 patients with liver cirrhosis and portal hypertension who were undergoing injection sclerotherapy following a variceal haemorrhage. SMS 201-995 reduced directly recorded intravariceal pressure by 38%, whereas reductions in the wedged hepatic venous pressure were around 17%. These observations suggest that SMS 201-995 may prove useful in treating bleeding oesophageal varices in the acute situation. Preliminary, promising data are shown in the results of a randomized controlled clinical trial in which SMS 201-995 plus injection sclerotherapy vs injection sclerotherapy are compared in patients with bleeding oesophageal varices. Furthermore, in experimental work associated stimulating effects of SMS 201-995 are shown on the function of the reticulo-endothelial system both in the liver and peripherally. These effects may prove useful by reducing the effects of endotoxaemia and possibly result in arresting further liver damage.

Animals↗
PubMed1986

A comparison of the effects of end-to-side portacaval shunting and side-to-side mesocaval shunting on hepatic haemodynamics in the dog.

Functional liver blood flow and hepatic artery flow were measured before and after either end-to-side portacaval or side-to-side mesocaval shunting in dogs. Functional liver blood fell by approximately 50% following both portacaval and mesocaval shunting. The hepatic artery response was variable after both portacaval and mesocaval shunts. It is concluded that side-to-side mesocaval shunts do not preserve hepatic blood flow or produce a greater compensatory increase in hepatic artery flow than conventional portacaval shunts.

Animals↗
PubMed1986

Effects of total and selective portasystemic shunting on hepatic haemodynamics and some aspects of liver function in the cirrhotic rat.

The effects of total and selective portasystemic shunting on hepatic haemodynamics and some aspects of liver function were studied in rats with dimethylnitrosamine-induced cirrhosis. Immediately following end-to-side portacaval shunting there were significant reductions in wedged hepatic venous pressure (WHVP) and liver blood flow. After side-to-side mesocaval shunting liver blood flow and wedged hepatic venous flow fell by approximately the same magnitude. Selective shunting (mesocaval 'H'-grafts and splenopancreaticocaval) preserved liver blood flow to a greater extent than total portasystemic shunting but had a less marked effect on WHVP. Furthermore, selective portasystemic shunting prevented liver atrophy and deterioration in liver function which was observed in rats following total portasystemic shunting. These results suggest that in the cirrhotic rat, selective portasystemic shunts which preserve functional liver blood flow and prevent liver atrophy and a deterioration in liver function do not produce such a marked decrease in WHVP as total shunts. Further studies in man are required to evaluate the relative advantages of total and selective portasystemic shunts.

Animals↗
PubMed1986

The effects of arterialisation of the portal stump on liver function and hepatic haemodynamics in cirrhotic rats with a portacaval shunt.

Liver blood flow (xenon-133 clearance method) and wedged hepatic venous pressure were studied in cirrhotic rats immediately after and 3 weeks following portacaval shunting (PCS), PCS and arterialisation of the portal stump with the left gastric artery (PCS-ART) or sham operation. Liver weight and function were compared 3 weeks after operation. Liver blood flow and wedged hepatic venous pressure were significantly reduced immediately after and 3 weeks following PCS. PCS-ART maintained liver blood flow and wedged hepatic venous pressure within the pre-operative range and prevented the liver atrophy and deterioration in liver function observed in rats with PCS. The results suggest that arterialisation of the portal vein with an artery which does not significantly increase sinusoidal pressure may be of benefit in preventing the early undersirable sequelae of PCS in man.

Animals↗
PubMed1986

Effects of somatostatin on hepatic haemodynamics in the cirrhotic rat.

Reports on the effects of somatostatin on hepatic haemodynamics in the cirrhotic patient have provided conflicting results. Therefore, we studied the effects of different modes and rates of somatostatin administration on hepatic haemodynamics in the cirrhotic rat. Portal pressure (PP), wedged hepatic venous pressure (WHVP), portal venous flow (PVF), liver blood flow (LBF) and systemic blood pressure were measured in rats with dimethylnitrosamine-induced cirrhosis. Somatostatin was administered as a rapid injection, a continuous infusion or as a bolus dose followed by a constant infusion. One group of rats with a previously constructed portacaval shunt received a bolus dose of somatostatin followed by a constant infusion. A rapid injection of somatostatin was attended by a rapid and significant fall in all the haemodynamic parameters measured (p less than 0.01). Continuous infusion of somatostatin [4 or 8 micrograms/kg body weight (BW) h] resulted in a gradual but significant reduction in PP, WHVP, PVF and LBF (p less than 0.05), but had no effect on systemic blood pressure. A bolus dose of somatostatin (2, 4 or 8 micrograms/kg BW over 2 min) resulted in a rapid decrease in PP, WHVP, PVF and LBF (p less than 0.01), the decreases being maintained by continuous infusion. In rats with a portacaval shunt a bolus dose of somatostatin (8 micrograms/kg BW) resulted in a rapid fall in WHVP and LBF, the decrease being maintained by a continuous infusion (8 micrograms/kg BW/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of alcohol on hepatic haemodynamics in the rat.

The effects of varying rates of alcohol infusion (0.015-0.12 mg/g body weight/min) on hepatic haemodynamics were studied in male Wistar rats. An infusion of 0.015 mg/g body weight/min alcohol had no significant effect on portal pressure (PP) or wedged hepatic venous pressure (WHVP). However, increasing rates of infusion of alcohol (0.03-0.12 mg/g body weight/min) progressively increased PP and WHVP, the maximum increase in PP occurring following an infusion of 0.12 mg/g body weight/min (6.5 +/- 0.5 - 10.3 +/- 0.6 mm Hg). The effect of varying rates of alcohol infusion on portal venous flow and liver blood flow was biphasic. Thus following an infusion of 0.03 mg/g body weight/min alcohol, liver blood flow (40.6 +/- 4.9 - 54.3 +/- 5.8 ml/100 g/min) and portal venous flow (28.6 +/- 2.9 - 41.3 +/- 4.1 ml/min) were increased. However, following infusions of 0.06 and 0.12 mg/g body weight/min alcohol, liver blood flow and portal venous flow were decreased. The results suggest that previous conflicting reports on the effects of alcohol on hepatic haemodynamics may be related to the dose of alcohol administered.

Animals↗
PubMed1986

Limits to parathyroid imaging with thallium-201 confirmed by tissue uptake and phantom studies.

Correct location by 201TI imaging of 48 parathyroids in 35 patients was related to size; 25 out of 26 parathyroids of mass greater than 1.0 g were correctly located, none of ten parathyroids less than 0.3 g was correctly located. In seven patients previously imaged, 108 microCi (4.0 MBq) of 201TI was injected when the thyroid was first exposed surgically. Subsequently weighed and histologically confirmed samples of parathyroid, thyroid, and skeletal muscle were counted against a standard in a well counter. Thallium-201 uptake, as %/g, did not differ between hyperplastic and adenomatous parathyroids. Mean parathyroid uptake was 0.018%/g, thyroid 0.01%/g, muscle 0.0026%/g of administered dose. Lower limits for correct location lay between 0.006-0.0149% of administered dose and between 0.25-0.8 g. Studies using a 201TI phantom containing small aliquots of 201TI at higher concentrations suggested approximately 0.0075% of the usual patient imaging dose as a lower limit for correct location.

Adenoma↗
PubMed1985

A prospective randomised controlled clinical trial comparing somatostatin and vasopressin in controlling acute variceal haemorrhage.

Twenty two patients were entered into a randomised controlled clinical trial comparing the efficacy of somatostatin and vasopressin in controlling acute variceal haemorrhage. Somatostatin was significantly more successful in controlling acute variceal haemorrhage than vasopressin (p = 0.003). Furthermore, no complications were observed during treatment with somatostatin.

Adult↗
PubMed1985

Effects of propranolol on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat.

The effects of systemic and intraportal administration of propranolol on hepatic haemodynamics were studied in cirrhotic and non-cirrhotic rats. In the non-cirrhotic rat systemic infusion of 4 micrograms (kg body wt)-1 min-1 propranolol significantly decreased portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow without affecting heart rate. Similar changes were observed in the cirrhotic rat following an infusion of 2 micrograms (kg body wt)-1 min-1 propranolol. Higher rates of propranolol infusion produced greater reductions in portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow in cirrhotic and non-cirrhotic rats but these changes were accompanied by a bradycardia. The reduction in portal pressure effected by propranolol was accompanied by an increased splanchnic vascular resistance. Intraportal injection of propranolol resulted in a rapid but transient fall in portal pressure. The decrease in portal pressure was sustained if propranolol was infused intraportally. The results indicate that propranolol effects a reduction in portal pressure via a combination of increased splanchnic vascular resistance, increased hepatic arterial resistance and reduced cardiac output. The observation that propranolol can significantly reduce portal pressure without affecting heart rate may be clinically important in the long-term management of portal hypertension. Furthermore, the rapid reduction in portal pressure following intravenous administration suggests that propranolol may be of value in the acute control of variceal haemorrhage.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Cell growth, cell division and cell size homeostasis in Swiss 3T3 cells.

By separating large and small 3T3 cells we show here that cell growth (in volume) after stimulation from quiescence is not 'autocatalytic'. Rather, large cells grow significantly more slowly, in relative terms, than small cells. It follows that 3T3 cells do not require a size control mechanism operating at the level of division timing in order to achieve cell size homeostasis.

Animals↗
PubMed1985

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↗