Search PubMed⌕ Search

Biomedical subjects

D M Nott

Publications and source records attributed to D M Nott.

At least 37 records · Page 2Linked to original sources

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↗

Upper limb venous gangrene, a lethal condition.

Venous gangrene of the upper extremity is rare. It was the mode of presentation in a 41-year-old woman who died 10 days later of heart failure due to acute myocardial infarction. There is evidence from this and previous publications that patients with this condition tend to have characteristics in common. Most have either advanced malignant disease or seriously impaired myocardial function and venous gangrene usually occurs as a pre-terminal event. Treatment should be directed primarily at the underlying illness but there may be a case for early amputation if permitted by the general condition of the patient.

Adult↗

ePTFE grafts for femoro-crural bypass--improved results with combined adjuvant venous cuff and arteriovenous fistula?

Patency rates for long prosthetic bypass grafts with standard anastomoses to single tibial or peroneal arteries are very poor. Adjuvant techniques employed with the aim of improving patency rates include arteriovenous fistula (AVF) at the distal anastomosis to accelerate blood flow above thrombotic threshold velocity (TTV) and a venous cuff (VC) or patch which may reduce or modify anastomotic myointimal hyperplasia within the recipient artery. In a consecutive series of 43 femoro-crural bypasses with ePTFE grafts, adjuvant AVF and VC procedures have been applied in combination. The results are compared with those of an antecedent series of 76 similar grafts with AVF alone and a contemporaneous series of 179 autologous vein grafts. All operations were undertaken for critical limb ischaemia with anastomosis to a single calf or pedal artery. The three groups were well matched for age, sex, diabetes, smoking history, previous surgery and the proportion with rest pain and tissue necrosis. The cumulative patency rate at 2 years for ePTFE grafts with combined AVF and VC was 62% compared to 28% for those with AVF alone and 68% for autologous vein grafts. The patency rate for prosthetic grafts with AVF and VC was significantly higher than AVF alone (p < 0.01) and did not differ significantly from vein grafts. Cumulative limb salvage rates for ePTFE grafts with AVF and VC were 68% at 1 year and 55% at 2 years compared to 38 and 35% for AVF alone and 78 and 69% for vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Intra-arterial injection of temazepam in drug abusers.

The effects of intra-arterial injection of Temazepam are described in 11 drug abusers admitted over a 6 month period. All patients suffered severe ischaemia, and injection into the radial artery invariably resulted in tissue loss leading to amputation. The pathogenesis and options for treatment are discussed.

Adult↗

Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia.

The lowest recurrence rates after inguinal hernia repair have been achieved by specialized hernia clinics. The Shouldice repair achieves success through application of a meticulous standardized operation carried out by specialist hernia surgeons. In a trial designed to rule out surgeon-dependent variables, 322 inguinal hernias were randomized prospectively to Shouldice repair or plication darn. Fifteen general surgeons operated on 322 patients. Fourteen surgeons in training not familiar with Shouldice repair received constant supervision for six repairs before independent operation. The mean (s.d.) patient age was 58.3(1.5) (range 20-84) years for Shouldice repair and 57.0(1.2) (range 18-85 years) for plication darn. The sex ratio (M:F) was 17:1 and right side to left side ratio 1.8:1. Six-week complication rates for wound infection (Shouldice repair, 5 per cent; plication darn, 4 per cent) and haematoma (Shouldice repair, 7 per cent; plication darn, 5 per cent) were similar in both groups. There were a similar number of sliding hernias in the Shouldice repair (14) and plication darn (20) groups. After a mean follow-up of 30 (range 24-48) months there were seven recurrences in the Shouldice group and four in the plication darn group (P > 0.05). The recurrences suggest that additional supervision of junior surgeons is required during the Shouldice repair learning period.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗