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Biomedical subjects

S A Jenkins

Publications and source records attributed to S A Jenkins.

At least 91 records · Page 5Linked to original sources

Effect of chronic ethanol ingestion on tissue RNA and blood flow in skeletal muscle with comparative reference to bone and tissues of the gastrointestinal tract of the rat.

1. The effects of feeding a diet containing ethanol as 36% of total calories for 4-5 weeks on muscle RNA content and blood flow was investigated in male rats weighing 150-250 g. Control animals were pair-fed the same diet in which ethanol was substituted by isocaloric glucose. 2. Chronic ethanol consumption reduced the capacity for type II (anaerobic, fast-twitch) fibre-rich skeletal muscles to synthesize protein as reflected by a decreased RNA/protein ratio. Type I (aerobic, slow-twitch) fibre-rich muscles were unaffected. 3. Ethanol feeding had no significant effect on cardiac output. Furthermore, the percentage of cardiac output to type I and type II fibre-rich muscles, bone and tissues of the gastrointestinal tract, i.e. stomach, small intestine and large intestine, was unaffected by ethanol consumption. Similarly, ethanol feeding had no effect on blood flow when it was calculated on the basis of tissue weight (ml min-1 g-1). 4. It was concluded that chronic ethanol feeding in the rat was associated with selective skeletal muscle dysfunction in the absence of changes in blood supply.

Alcoholism↗

Use of somatostatin in the management of pancreatic haemobilia.

An elderly man, not previously known to have chronic pancreatitis, presented with haematemesis and melaena which was endoscopically diagnosed as haemobilia. Retrograde cholangiopancreatography showed blood clot in both the common bile duct and the pancreatic duct and the computed tomographic scan appearances were those of gross calcific chronic pancreatitis. Despite active bleeding, it was not possible to demonstrate its source at angiography, thus precluding therapeutic embolization. Thirty six hours after commencing an infusion of somatostatin, repeat endoscopy showed no evidence of active or recent bleeding. The infusion was continued for 5 days during which time he had no further bleeding.

Aged↗

Preduodenal mechanisms in initiating gallbladder emptying in man.

The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.

Adolescent↗

The enterohepatic circulation of perhexiline metabolites in the male Wistar rat.

1. The biliary excretion of some perhexiline metabolites has been assessed in male Wistar rats with biliary cannulation. 2. After intragastric administration of perhexiline maleate (2 mg/kg body weight) multiple perhexiline metabolites were detected in bile. 3. When aliquots of this metabolite-laden bile were administered intraduoduodenally to further 'recipient' rats with biliary cannulation, similar metabolites were detected in the bile of these rats, but at reduced concentrations equivalent to 30-35% of those present in the bile of 'donor' rats. 4. These findings indicate that in the male Wistar rat, there may be substantial enterohepatic circulation of some perhexiline metabolites.

Animals↗

A model of the hepatic perfusion index in the rat.

The hepatic perfusion index (HPI) is an indicator of the relative hepatic arterial to total liver blood flow as measured by dynamic flow scintigraphy. Hitherto, accurate assessment of the HPI in small animals has not been possible because of methodological difficulties. A reproducible method for measuring the HPI by dynamic scintigraphy in rats is described using a rapid intraventricular bolus administration of 0.04 ml 99Tcm sulphur colloid. There was no significant difference between the HPI determined by dynamic scintigraphy and and that calculated from absolute measurements of hepatic arterial and total liver blood flow. These results indicate that the HPI derived by dynamic scintigraphy in the rat is a true estimate of the ratio of the hepatic arterial to total liver blood flow.

Animals↗

Changes in the hepatic perfusion index during the growth and development of experimental hepatic micrometastases.

Micrometastases were induced in Fisher rats using an intraportal inoculation of 0.2 ml of 8 x 10(7) Walker carcinosarcoma cells. A control group received normal saline. The hepatic perfusion index (HPI) was measured during the growth and development of micrometastases. The HPI at 4 days (0.51 +/- 0.008) and at 6 days (0.65 +/- 0.16) was significantly raised when compared to controls (0.31 +/- 0.07) and at 2 days after inoculation (0.31 +/- 0.06). Hepatic artery flow did not change throughout the study period. However, portal venous inflow was decreased significantly at 4 and 6 days (0.57 +/- 0.16 and 0.55 +/- 0.11) when compared to controls (0.96 +/- 0.34). These results indicate that the change in the hepatic perfusion index is related to a decrease in portal venous inflow. The decrease in portal venous inflow could be a mechanical effect of the micrometastases on intrahepatic blood flow or to increased arteriovenous shunting.

Animals↗

Induced hepatic arterial blockade by degradable starch microspheres in the rat.

Degradable starch microspheres (DSM, Spherex) have been shown to cause intermittent blockage of hepatic arterial flow and to increase the concentration of regionally injected cytotoxics. The Spherex monitoring system has been developed by Pharmacia, Sweden to establish the correct dose of DSM to optimize hepatic arterial blockade. Groups of normal rats received varying dosages of DSM and co-injected methylene diphosphonate (MDP) in order to reproduce the effect of reduction of passing fraction and marker flow rate as determined by the Spherex monitoring system. A flow reduction and significant decrease in passing fraction was achieved on injection of 4 mg of DSM via the hepatic artery.

Animals↗

Relationship between gastric emptying of a solid meal and emptying of the gall bladder before and after vagotomy.

Little is known of the temporal and quantitative relationships between emptying of the stomach and of the gall bladder in patients with duodenal ulcer before and after vagotomy. A non-invasive double isotope technique was used to investigate these relationships in 27 patients with a duodenal ulcer, before and after operation-truncal vagotomy and pyloroplasty (TV + P; n = 15) and highly selective vagotomy (HSV; n = 12). A further 25 patients were studied after operation (TV + P, n = 20: HSV, n = 5). 99Tcm-EHIDA was used as the biliary tracer and 113Inm bran as the gastric content tracer. In patients with a duodenal ulcer before surgery and in 16 of the 17 patients studied after HSV, the patterns of gall bladder emptying were similar to those previously found in normal subjects. In 60% of patients after TV + P, patterns of gall bladder emptying were altered and the onset of gall bladder emptying was significantly delayed (p less than 0.001) compared with unoperated patients and patients with a HSV. The rate of gall bladder emptying did not correlate with the rate of gastric emptying in any of the patients studied. These observations suggest that TV + P, but not HSV, causes considerable alteration in coordination of gall bladder and gastric emptying.

Duodenal Ulcer↗

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↗

Altered monocyte function in patients with benign breast disease.

Monocyte migration, lysozyme production and phagocytosis was studied in 34 patients with fibroadenosis, 28 patients with fibroadenoma and 48 healthy female controls. In patients with fibroadenosis and fibroadenoma, monocyte migration and phagocytic activity were significantly reduced when compared to controls (P less than 0.001). Conversely, lysozyme production by monocytes from patients with benign breast disease was significantly higher than in controls (P less than 0.001). In 20 patients with benign breast disease, there was no significant difference in monocyte function before and 3 months after operation. The observed impairment of monocyte function in fibroadenosis and fibroadenoma would not appear to be the result of abnormal blood biochemistry or due to a direct serum inhibitor, but is probably related to an intrinsic cellular defect. Further studies are required to evaluate the significance of impaired monocyte function in the pathophysiology of benign breast disease.

Adenofibroma↗

Alteration in monocyte function in patients with breast cancer.

Migration, phagocytosis and lysozyme production of peripheral monocytes from 36 patients with breast carcinoma was compared with a group of 36 healthy controls. A significant reduction in monocyte random migration and migration towards a chemotactic agent (P less than 0.001) was observed in patients with breast cancer. Furthermore monocyte phagocytic activity was also significantly decreased (P less than 0.001) in breast cancer patients compared to the controls. In contrast lysozyme production by peripheral monocytes was significantly increased in patients with breast cancer compared to controls (P less than 0.001). The changes in monocyte function in patients with breast carcinoma were not due to abnormal blood biochemistry or to direct continuous serum inhibitors, suggesting that the defect may be intrinsic. This defect in monocyte function may play an important role in the control of malignancies by cellular immune processes.

Adult↗

Transformation of blood monocytes to giant cells in vitro from patients with breast cancer.

Monocytes from patients with breast cancer and from control subjects were cultured under agarose for 6 days. Giant cell formation occurred in 32 out of the 36 patients with breast cancer (89 per cent). In contrast giant cell formation was only observed in two of the control subjects (6 per cent). Menstruation and menopause had no effect on giant cell formation. Furthermore, under the experimental conditions of this study, it seems unlikely that serum factors, lymphokines or phagocytic stimulators induced giant cell formation. The results therefore, suggest that giant cell formation may be initiated by viruses already present in the monocytes from patients with breast cancer. Further studies are required to confirm this hypothesis and to elucidate the significance of giant cell formation in the pathogenesis of breast cancer.

Breast Neoplasms↗

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↗

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↗