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Biomedical subjects

S A Jenkins

Publications and source records attributed to S A Jenkins.

At least 73 records · Page 4Linked to original sources
PubMed1992

A prospective randomised controlled trial comparing the efficacy of somatostatin with injection sclerotherapy in the control of bleeding oesophageal varices.

Since previous reports have suggested that somatostatin may be of value in the control of acute variceal haemorrhage, we compared its efficacy with that of injection sclerotherapy in a randomised controlled clinical trial. Eighty consecutive patients with endoscopically-proven severe variceal bleeding were randomised to injection sclerotherapy (n = 41) or somatostatin (n = 39) given as a continuous infusion of 250 micrograms/h for 5 days plus daily bolus administration of 250 micrograms. The efficacy of injection sclerotherapy and somatostatin infusion in controlling haemorrhage and preventing rebleeding (censored at 5 days), mortality (censored at 28 days) and complications was compared. The aetiology of the portal hypertension and transfusion requirements was similar between the two groups, but there were more patients with severe liver disease (Child's C) in the somatostatin group. There was no significant difference between the two treatments in the initial (p = 1.0) or overall control of bleeding (p = 0.58). Furthermore, somatostatin was as effective as injection sclerotherapy in controlling bleeding in patients with severe liver disease or in those actively bleeding at the time of their endoscopy. The relative risk of rebleeding whilst receiving somatostatin compared to injection sclerotherapy was 1.39 [95% Confidence Interval (CI) 3.73; 0.52], but this was reduced to 0.98 (95% CI 0.37; 2.67) when readjusted for Child's grading, the only prognostic factor shown to be of significance. Mortality was not significantly different between the two groups of patients (p = 0.31). The relative risk of dying whilst receiving somatostatin compared to injection sclerotherapy was 1.6 (95% CI 3.93; 0.66) but was reduced to 1.03 (95% CI 0.47; 2.47) when adjusted for Child's grading, the only significant prognostic factor. Complications in the somatostatin group were minor and less frequent than after injection sclerotherapy. The results of this study indicate that somatostatin is a safe treatment, which is as effective an endoscopic injection sclerotherapy for acute variceal bleeding.

Adult↗
PubMed1992

The effects of sandostatin (Octreotide, SMS 201-995) infusion on splanchnic and hepatic blood flow in an experimental model of hepatic metastases.

Manipulation of hepatic blood flow may improve drug delivery to hepatic tumour. Somatostatin and its long acting analogues are known to elicit effects upon hepatic and splanchnic blood flow in experimental animals and patients with portal hypertension. This study investigates the effects of SMS 201-995 (sandostatin) infusion on hepatic, splanchnic and tumour blood flow in an experimental model of liver metastases. Hepatic tumour was induced by the intraportal inoculation of 10(6) HSN sarcoma cells and blood flow measured using the dual reference microsphere method before and after infusion of SMS 201-995. There was a significant decrease in hepatic arterial flow and a significant increase in the tumour:liver blood flow ratio associated with a marked reduction in blood flow to normal hepatic parenchyma. Portal venous inflow and tumour blood flow were not significantly affected. SMS 201-995 infusion may lead to preferential delivery of concomitantly injected cytotoxic drugs to hepatic tumour. In addition, the reduction in growth of hepatic tumour may be due to a reduction in nutritive, arterial blood flow to hepatic tumour.

Animals↗
PubMed1992

Management of massive upper gastrointestinal haemorrhage from multiple sites of peptic ulceration with somatostatin and octreotide--a report of five cases.

Surgical management of massive upper gastrointestinal bleeding after failed medical treatment may be hazardous because of diffuse bleeding from several sites, further complicated in some patients by intercurrent disease, age, or previous surgery. Experience with combined somatostatin and octreotide therapy in five such patients is described. All were treated initially with either intravenous somatostatin (250 micrograms/hour) or octreotide (Sandostatin) (50 micrograms/hour) for periods ranging from three to five days, after which they were given subcutaneous octreotide (50 or 100 micrograms three times daily). Bleeding was controlled by this regimen in all cases. The patients were all discharged from hospital on either ranitidine (n = 4) or omeprazole (n = 1). Repeat endoscopy at the end of the treatment period with somatostatin and octreotide (n = 1) or four weeks after discharge (n = 3) showed complete healing of the bleeding sites. Somatostatin and octreotide may be of value in controlling severe upper gastrointestinal bleeding in patients in whom surgery is hazardous because of bleeding from several peptic lesions further complicated in some by intercurrent disease or age.

Adult↗
PubMed1992

The management of persistent or recurrent variceal bleeding after injection sclerotherapy by somatostatin.

Sixteen patients with persistent (n = 11) or recurrent (n = 5) variceal bleeding after injection sclerotherapy and balloon tamponade were treated with an intravenous infusion of somatostatin 250 micrograms/h. Somatostatin infusion successfully controlled the bleeding in 15 of the 16 patients but one rebled after 72 h of treatment. In one patient with poor liver function (Child's C) bleeding was not controlled by somatostatin, further injection sclerotherapy or balloon tamponade of the oesophagus. The results of this study, although uncontrolled and with a small number of patients, suggest that somatostatin is a very effective treatment for the control of post-injection sclerotherapy variceal bleeding.

Adult↗
PubMed1992

Somatostatin in acute bleeding oesophageal varices. Clinical evidence.

Following the demonstration that somatostatin lowered portal pressure in cirrhotic patients with portal hypertension, 2 uncontrolled reports suggested that the hormone might be useful in the control of acute variceal haemorrhage. Subsequently, a number of randomised controlled trials have indicated that somatostatin may have an efficacy as good as or better than either vasopressin or combined vasopressin and nitroglycerin therapy and is associated with fewer side effects. Somatostatin has an efficacy comparable to balloon tamponade, histamine-2-receptor antagonists and injection sclerotherapy. One double-blind randomised controlled trial demonstrated a significant benefit of somatostatin over placebo in the control of variceal bleeding whereas a second did not show any significant difference between treatments. In all the controlled trials, the average control rate achieved with somatostatin administration was 69% and it was not associated with any major side effects. Somatostatin administration has also been shown in uncontrolled series to be very effective in controlling postinjection sclerotherapy bleeding from the varices per se, and from oesophageal ulcers and oesophagitis. Few data are available on the long acting analogue of somatostatin, octreotide, but preliminary data suggest that it may be as effective and safe as the native hormone in controlling the acute variceal bleeding and postinjection sclerotherapy haemorrhage. It is concluded that there may be a case for instituting somatostatin therapy as soon as the patient enters hospital to facilitate sclerotherapy, and for continuing treatment for 5 days after sclerotherapy when the risk of recurrent bleeding is highest.

Acute Disease↗
PubMed1992

The effect of portal venous flow on the washout of a regionally injected marker substance 99mTc-methylene diphosphonate after hepatic arterial blockade with degradable starch microspheres.

Patients with hepatic metastases derived from colorectal carcinoma have a poor prognosis. Regional chemotherapy, either alone, or combined with agents such as degradable starch microspheres (DSM) that reduce or abolish intrahepatic arterial flow and potentiate the delivery of cytotoxics to hepatic metastases, have not significantly improved survival. We have investigated one positive mechanism, namely the effect of portal venous washout of cytotoxics, for the poor efficacy of drugs administered either alone or in combination with DSM via the hepatic artery in the rat. Using a radiolabelled marker, 99mTc-methylene diphosphonate (MDP), to represent a cytotoxic drug, the initial studies indicated that with the hepatic artery and portal vein clamped, a volume of 0.05 ml of the marker administered via the hepatic artery resulted in the most uniform intrahepatic distribution with minimal washout into the systemic circulation (21 +/- 3.7%). When the hepatic artery was clamped, the washout of MDP was reduced from 100% (with clamps on the portal vein and hepatic artery) to 84.2 +/- 7.7%. DSM administered concomitantly with MDP, resulted in a greater reduction of the portal venous washout of the marker (63 +/- 2.4%). Administration of DSM and MDP via the hepatic artery and with the portal vein clamped further reduced the washout of the marker to (21 +/- 2.26), results similar to those observed with inflow vessel clamps. Following restoration of portal venous flow, there was a rapid washout of 53.7 +/- 7.6% of the marker into the systemic circulation. The results of this study suggest that portal venous washout of regionally delivered cytotoxics, either alone or in combination with DSM, offer an explanation for the poor efficacy of regional chemotherapy in improving the prognosis of patients with hepatic metastases.

Animals↗
PubMed1992

Numerical taxonomy of Bacteroides and other genera of Gram-negative anaerobic rods.

A numerical taxonomy was performed on 157 cultures (141 different strains) of species of Bacteroides, Polyphyromonas, Prevotella [not Prevotella (Labroue, 1976)] and Fusobacterium. Isolates were each tested for 111 phenotypic characters which included possession of constitutive enzymes, fermentation of specific carbohydrates, gas chromatographic analysis of metabolic end-products and of cellular carboxylic acid composition. Computation of similarity coefficients was followed by a single-linkage cluster analysis. At the 94% similarity level, the following groupings at genus level were apparent: (1) Bacteroides ureolyticus; (2) Fusobacterium mortiferum, F. necrogenes, F. necrophorum, F. nucleatum and F. varium; (3) B. caccae, B. distasonis, B. eggerthii, B. fragilis, B. merdae, B. ovatus, B stercoris, B. thetaiotaomicron, B. uniformus and B. vulgatus; (4) B. splanchnicus; (5) Porphyromonas asaccharolytica; (6) B. bivius (Prevotella bivia); (7) B. disiens (P. disiens); (8) B. intermedius (P. intermedia);and (9) B. melaninogenicus (P. melaninogenica). Single isolates of B. ruminicola (P. ruminicola), B. denticola (P. denticola) and B. capillosus did not cluster with other strains.

Bacterial Typing Techniques↗
PubMed1991

Changes in hepatic haemodynamics and hepatic perfusion index during the growth and development of hypovascular HSN sarcoma in rats.

Experimental liver tumours were induced in the Hooded Lister rat by the intraportal inoculation of 10(6) HSN sarcoma cells. The hepatic perfusion index was raised 10 days after the inoculation of cells (at the micrometastatic stage) and when overt tumour was present 20 days after inoculation. Overt tumours were hypovascular compared with normal liver. Portal venous flow and portal venous inflow fell significantly when the hepatic perfusion index was increased, but hepatic arterial flow did not alter. Portal vascular resistance and splanchnic vascular resistance were both increased in tumour-bearing animals but portal pressure, arteriosystemic shunting and portosystemic shunting did not increase significantly at any stage during the growth of hepatic tumour. These findings confirm that the hepatic perfusion index can be elevated in the presence of both micrometastic and overt hepatic tumour and that the changes are not due to either arteriosystemic shunting or mechanical portal venous obstruction.

Animals↗
PubMed1991

Treatment of severe postvagotomy/postgastrectomy symptoms with the somatostatin analogue octreotide.

Fourteen patients with severe and persistent postvagotomy/postgastrectomy symptoms were entered into a trial of treatment with the somatostatin analogue octreotide, 50 micrograms twice daily 30 min before meals being self-administered by subcutaneous injection. Six of the seven patients completing the 3-month trial showed sustained overall improvement of symptoms. The remaining patients were unhelped by treatment or developed unwanted effects. Six of eight patients with dumping syndrome showed sustained improvement of dumping symptoms during treatment. Bile vomiting was relieved in three of four patients with this complaint. Diarrhoea accompanying dumping showed a variable response to treatment, with improvement in three patients and no change or worsening of this symptom in five. Two patients with severe postvagotomy diarrhoea alone showed no improvement. Four patients with unwanted effects and three patients who found no benefit stopped the trial medication early. Four further patients reported mild or transient side-effects. For patients with severe postvagotomy/postgastrectomy symptoms, a trial of octreotide seems justified when significant dumping symptoms are present and other treatment options have been exhausted.

Adult↗
PubMed1991

The management of gastrointestinal haemorrhage by somatostatin after apparently successful endoscopic injection sclerotherapy for bleeding oesophageal varices.

Twenty-two patients who experienced a severe haemorrhage from either oesophagitis (n = 8) or ulcers (n = 14) following injection sclerotherapy of their oesophageal varices were treated with intravenous administration of somatostatin (250 micrograms/h). Somatostatin was effective in controlling haemorrhage and preventing rebleeding in all eight patients bleeding from oesophagitis and in 12 of the 14 patients bleeding from oesophageal ulcers. In two patients with ulcers, haemorrhage persisted despite two periods of concominant balloon tamponade and somatostatin infusion and bleeding was eventually controlled by repeated hourly bolus injections of the hormone for 24 h superimposed on the continuous infusion. The results of this study suggest that somatostatin is an effective and safe treatment for the control of bleeding from either oesophagitis or ulcers following injection sclerotherapy of oesophageal varices.

Combined Modality Therapy↗
PubMed1991

The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour.

Regional chemotherapy for colorectal liver metastases has not demonstrated a convincing survival benefit over systemic chemotherapy. This may be due to poor delivery of chemotherapeutic drugs to hypovascular liver tumour. Since vasoactive agents may influence hepatic blood flow this study investigated the effects of systemic and regional vasoconstrictors on the delivery of a regionally delivered marker in an experimental model of liver tumour. Systemic administration of angiotensin II caused a significant retention of marker in normal liver, but not in tumour compared to controls. Regional delivery of angiotensin II and phenylephrine caused significantly greater retention of marker in tumour than liver with an overall 4-fold increased retention of marker one minute after its injection. Ninety minutes after injection there was still significant retention of marker compared to control animals. Regional delivery of hepatic artery vasoconstrictors increase delivery of marker and may increase delivery of chemotherapeutic drug to liver tumour.

Angiotensin II↗
PubMed1991

The effects of vasopressin infusion on hepatic haemodynamics in an experimental model of liver metastases.

Vasoactive drugs have a variety of effects upon splanchnic and hepatic haemodynamics which may alter tumour blood flow and potentiate the delivery of a chemotherapeutic drug to hepatic tumour. We have investigated the effects of vasopressin infusion on hepatic tumour blood flow in an experimental model of liver tumour. Hepatic tumour was induced by the intraportal inoculation of HSN sarcoma cells. Hepatic and splanchnic blood flow was determined using a dual reference microsphere technique before and after an intravenous infusion of vasopressin at a dose of 0.1 mU kg-1 min-1 for 10 min. There was a significant increase in systemic arterial blood pressure associated with a rise in portal venous inflow (P less than 0.01, Wilcoxen Signed rank Test) and a significant fall in hepatic arterial flow (P less than 0.05). The tumour: liver blood flow ratio was significantly increased by vasopressin infusion (P less than 0.02). Vasopressin infusion decreases hepatic arterial flow and increases tumour blood flow which may potentiate the delivery of a regionally delivered chemotherapeutic drug to hepatic tumour.

Animals↗
PubMed1991

Changes in hepatic haemodynamics in rats with overt liver tumour.

Overt liver tumour was induced in Fisher rats by intraportal administration of 1.6 x 10(7) Walker carcinosarcoma cells. Control groups of rats received similar volumes of dead cells or saline intraportally. All animals were studied at 3 weeks when overt tumour was present. The Hepatic Perfusion Index (HPI) was significantly raised in rats with overt tumour compared to both groups of control animals. Portal flow and portal venous inflow were significantly reduced in the presence of overt tumour but hepatic arterial flow did not alter. These observations suggest that the alteration in the HPI in the presence of overt tumour results from an alteration in portal venous flow and inflow even though the blood supply to the tumour is principally derived from the hepatic artery. The changes in hepatic haemodynamics in the presence of tumour were accompanied by a reduction in portal pressure, an increase in splanchnic vascular resistance and an increase in the degree of arteriovenous shunting through the liver. Portal vascular resistance was unchanged. These findings indicate that the presence of overt hepatic tumour results in gross derangements of hepatic blood flow. These changes must be taken into consideration when attempting to potentiate the delivery of cytotoxic drugs to hepatic tumour by manipulation of hepatic haemodynamics.

Animals↗
PubMed1991

Evaluation of the RAPID ID 32A system for the identification of Bacteroides fragilis and related organisms.

This study evaluated the ability of a rapid identification system for anaerobic bacteria, ATB 32A, now renamed RAPID ID 32A (API-bioMérieux UK Ltd., Basingstoke), to identify accurately 74 strains of the 'B. fragilis group'. ATB 32A identified correctly 78.4% of strains to species level, without supplemental tests. The percentage of strains identified to species level rose to 94.6% when a supplementary test (advised by bioMérieux) for catalase production was used to differentiate between Bacteroides ovatus and Bacteroides uniformis. RAPID ID 32A is a rapid, accurate method for the identification of members of the 'B. fragilis group' isolated within a routine clinical laboratory.

Bacteroides↗
PubMed1989

Variceal haemorrhage after failed injection sclerotherapy: the role of emergency oesophageal transection.

In a planned sequential policy for the emergency control of continued bleeding from oesophageal varices, oesophageal transection was performed after failure of conservative treatment, including injection sclerotherapy. In 15 patients who underwent emergency oesophageal transection, bleeding was controlled by operation in the majority (87 per cent), but 11 of the 15 patients died in hospital. Mortality in patients with poor liver function (Child's C) was 100 per cent, the majority of deaths resulting from hepatic and renal failure. The results of this study suggest that emergency oesophageal transection to control acute variceal haemorrhage is associated with a poor prognosis in patients with poor liver function and questions its role in a sequential emergency treatment policy.

Adult↗
PubMed1989

Changes in the hepatic perfusion index during the development of experimental hepatic tumours.

A model of microscopic liver tumour has been developed in the Fisher rat by intraportal injection of 1.6 x 10(7) Walker 256 carcinosarcoma cells. Rats were studied at 2, 4 and 6 days after the inoculation of live Walker cells. A control group received dead Walker cells. No tumour was visible in control groups at 2, 4 and 6 days after inoculation. Similarly in rats injected with live cells no tumour was visible at 2 days after inoculation but at 4 and 6 days the percentage hepatic replacement was (mean +/- s.d.) 7.0 +/- 2.3 and 27.9 +/- 6.80 respectively. The hepatic perfusion index was significantly raised at 4 and 6 days after inoculation of live cells compared with control animals and those receiving viable cells after 2 days inoculation. Portal flow and portal venous inflow were significantly reduced when the hepatic perfusion index increased but hepatic arterial flow did not alter. Changes in the hepatic haemodynamics were accompanied by increases in the portal and splanchnic vascular resistance and an increase in the amount of arteriovenous shunting through the liver. These findings confirm studies that the hepatic perfusion index is useful in the detection of occult liver metastases but that the change is not a consequence of an increase in the hepatic arterial flow.

Animals↗
PubMed1989

Effects of a somatostatin analogue (SMS 201-995) on the growth and development of hepatic tumour derived by intraportal injection of Walker cells in the rat.

Administration of a long active analogue of somatostatin, SMS 201-995 (2 micrograms subcutaneously twice a day) for 3 weeks after intraportal administration of Walker cells significantly inhibited their growth and development in the liver. This was not due to a direct cytotoxic effect of the analogue on Walker cells whose growth was stimulated in vitro. Furthermore, SMS 201-995 had no effect on the growth of Walker cells implanted into the thigh of rats suggesting that the inhibitory action of the analogue could be confined to tumour cells growing in the liver. Further studies suggested that the inhibitory effect of SMS 201-995 on the growth of Walker cells in the liver could be related to a marked stimulation of the hepatic reticuloendothelial system, by a reduction in portal venous flow in the early stages of treatment or by a combination of these effects. Further studies are required to delineate more precisely the mechanism whereby SMS 201-995 inhibits the growth of hepatic tumour derived from intraportal administration of Walker cells.

Animals↗