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Biomedical subjects

H Kynaston

Publications and source records attributed to H Kynaston.

6 recordsLinked to original sources

Octreotide inhibits the growth and development of three types of experimental liver metastases.

A study was performed to assess the effects of octreotide on the growth and development of liver metastases in rats. Tumour was induced by intraportal injection of three tumorigenic cell lines (the fibrosarcoma HSN and colonic adenocarcinomas K12/Tr and WB2054M) in syngeneic rats. Octreotide treatment (2 micrograms subcutaneously for 3 or 4 weeks) was started 18 h and 1 week after tumour induction; a delay in treatment of 1 week allowed micrometastases to develop. Treatment with octreotide significantly (P < 0.001) reduced the median hepatic replacement of liver by tumour compared with that of control rats given saline (controls: HSN 76.4 per cent, K12/Tr 17.5 per cent, WB2054M 43.9 per cent; octreotide treatment delayed 18 h: HSN 2.7 per cent, K12/Tr 0.6 per cent, WB2054M 1.3 per cent; octreotide treatment delayed 1 week: HSN 9.3 per cent, K12/Tr 2.5 per cent, WB2054M 2.3 per cent). These results clearly indicate that octreotide significantly inhibits the growth and development of experimental liver metastases. Further studies are required both to delineate the mechanism of action and to investigate these effects in a clinical setting.

Animals

Effect of octreotide infusion on hepatic and tumour blood flow in two experimental models of liver metastases.

OBJECTIVE: To investigate the effects of octreotide infusion on hepatic and tumour blood flow in rats with experimentally induced liver tumours. DESIGN: Blood flow was determined in tumour-bearing rats using a dual reference microsphere technique before and after intravenous infusion of octreotide. METHODS: Tumours were induced in syngeneic rats by intraportal injection of K12-Tr and WB2054-M adenocarcinoma cells. Hepatic arterial and portal venous inflow, tumour blood flow and systemic arterial pressure were determined before and after octreotide infusion (0.05 microgram/min). RESULTS: In rats with K12-Tr tumours there was no change in tumour blood flow, hepatic arterial flow or portal venous inflow after octreotide infusion. In contrast, in rats with WB2054-M tumours, octreotide infusion resulted in a significant reduction in the blood flow to the hepatic tumour (from 0.37 to 0.135 ml/min/g) but had no effect on hepatic artery or portal venous inflow. CONCLUSION: The reduction in blood flow to tumours derived from WB2054-M cells could, at least in part, explain the inhibitory effect of octreotide on the growth and development of these tumours. However, octreotide had no effect on blood flow to tumours derived from K12-Tr cells, suggesting that the analogue must inhibit tumour growth by other mechanisms.

Adenocarcinoma

Octreotide, the reticuloendothelial system, and experimental liver tumour.

The inhibitory effect of octreotide on the growth of liver tumour is probably mediated (at least in part) by stimulation of the hepatic reticuloendothelial system (RES) activity. This study therefore investigated the effect of octreotide on the hepatic and splenic RES (assessed by the uptake of technetium 99m labelled albumin colloid, 99mTc-AC) in normal and tumour bearing rats and in animals treated with gadolinium chloride. The effects of gadolinium chloride and octreotide alone or in combination on the growth of liver tumour were also studied. Octreotide significantly stimulates both hepatic and splenic uptake of 99mTc-AC in normal rats and tumour bearing rats. In controls, the uptake of 99mTc-AC was significantly reduced by gadolinium chloride and was not changed by octreotide. RES blockade with gadolinium chloride significantly increased (p < 0.001) tumour growth compared with controls (hepatic replacement 42%; 95% confidence intervals (CI), 27.6 to 56.4 v 16.7%, 95% CI, 11.1 to 21.3%) whereas octreotide significantly inhibited (p < 0.001) the percentage hepatic replacement by tumour (0.7%; 95% CI, 0 to 2.3 v 16.7%; 95% CI, 11.1 to 21.3). This study highlights the importance of the RES in the development of liver tumour. Furthermore, octreotide inhibited the growth of liver tumour in rats with RES blockade, albeit to a lesser degree than in normal animals. These findings suggest that octreotide inhibits the growth of hepatic tumour by mechanisms other than stimulation of RES activity.

Animals

A prospective randomized trial comparing a modified needle suspension procedure with the vagina/obturator shelf procedure for genuine stress incontinence.

OBJECTIVE: To compare two procedures for the treatment of genuine stress incontinence in patients selected randomly. PATIENTS AND METHODS: Fifty patients with proven genuine stress incontinence were randomized prospectively over a 3 year period to be treated either by a modified needle suspension (MNS) (n = 26) or by a vagina/obturator shelf (VOS) (n = 24) procedure. RESULTS: In patients who had not undergone previous surgery for incontinence, the VOS procedure was superior with 12 of 14 patients achieving continence compared with eight of 15 patients in the MNS group (P < 0.05). In women who had undergone previous surgery seven of 11 were continent following MNS compared with five of 10 after a VOS procedure. Both techniques had a much lower continence rate when compared with a classical colposuspension operation which was reported in a previous series. CONCLUSION: As a primary procedure VOS was more successful than MNS. In patients who had undergone previous surgery for incontinence neither procedure gave acceptable results.

Female

Reticuloendothelial stimulation: levamisole compared.

PURPOSE: Levamisole in combination with 5-fluorouracil is an effective adjuvant for the treatment of resected Dukes stage C colon cancer. Since the mechanism of action of levamisole is not known, we have investigated its effects on hepatic and splenic reticuloendothelial system (RES) activity in the rat and compared the effect of levamisole with other known RES stimulators. METHODS: The hepatic and splenic uptake of an intravenous dose of technetium-99m-sulfur colloid has been used to measure RES activity in rats treated with levamisole, glucan, zymosan, chlormethiazole, octreotide, and saline. RESULTS: Levamisole significantly increased the hepatic uptake of technetium-99m-sulfur colloid and is comparable in its effect to the other RES stimulators. In contrast, levamisole has no effect on splenic RES activity. CONCLUSION: RES function is considered to be a potentially important factor in the development of liver metastases, and the stimulatory effect of levamisole on the hepatic RES may partly explain its efficacy as an adjuvant treatment in colon cancer.

Animals

Amyloid tumour of the urethra presenting as non-specific urethritis.

Amyloid tumour involving the urethra is a well recognised but rare occurrence. Chronic inflammation secondary to gonococcal urethritis is thought to be a possible predisposing factor. We report the case of a young man who presented with non-gonococcal urethritis and haematuria and was subsequently found to have primary amyloid of the urethra.

Adult