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Biomedical subjects

D M Nott

Publications and source records attributed to D M Nott.

At least 19 recordsLinked to original sources

Increasing hepatic arterial flow to hypovascular hepatic tumours using degradable starch microspheres.

The effect of degradable starch microspheres (DSM) on the intrahepatic distribution of a low molecular weight marker, 99Tcm-labelled methylene diphosphonate (MDP), was studied in rats with hypovascular HSN liver tumours. MDP was injected regionally, via the hepatic artery, alone or co-administered with DSM, with or without subsequent occlusion of either the hepatic artery or the portal vein. Tumour vascularity was measured with 57Co-labelled microspheres. Co-injection with DSM immediately significantly increased hepatic retention of marker in both tumour (T) (median 22.40 (range 16.82-39.58)% injected dose) and normal liver (N) (9.08 (4.85-12.59) %ID) the greater effect seen in T (P < 0.01). After DSM degradation, very little MDP remained in N (0.61 (0.28-1.40) %ID) but there was significant retention in T (10.01 (6.73-20.28) %ID, P < 0.01). Clamping the hepatic artery had minimal effect on the retention of MDP when administered alone. Regional injection of 16.5 microM 57Co microspheres resulted in a N:T ratio of 2.25:1. Concomitant injection of the 40 microM DSM was 57Co microspheres reversed this ratio to 1:2. The results indicate that DSM selectively enhances the retention of MDP to a hypovascular hepatic tumour, not by causing intra-tumour stasis, but by directing a greater arterial flow to hypovascular areas in the liver.

Animals

Smoking, hypertension, and colonic anastomotic healing; a combined clinical and histopathological study.

BACKGROUND: Large bowel anastomotic breakdown occurs as a result of perianastomotic ischaemia. Preservation of the macroscopic arterial supply to the perianastomotic tissues is vital, but little is known about the influence of microvascular disease on anastomotic healing. AIMS: To study the associations between risk factors for macrovascular disease, the presence of colonic microvascular disease, and the incidence of anastomotic dehiscence. PATIENTS: 147 consecutive colonic surgery patients. METHODS: The prevalence of smoking, hypertension, diabetes, and ischaemic heart disease were established retrospectively from patient notes. These risk factors were correlated with histopathological assessment of resection margin vasculature and clinical follow up. RESULTS: Smoking and hypertension were significantly associated with an increased incidence of anastomotic dehiscence and microvascular disease. Microvascular disease was positively correlated with an increased incidence of anastomotic dehiscence. CONCLUSIONS: Microvascular disease predisposes to anastomotic breakdown. This effect may in part be due to vasospasm in the diseased vessels, which are hypersensitive to serotonin, a vasoactive amine known to be present in increased quantities in the serum of smokers, hypertensives, and after surgery. Treatment with serotonin antagonists in the perioperative period may be beneficial to anastomotic healing, helping to maintain microvascular flow.

Aged

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

Assessment of feasibility for endovascular prosthetic tube correction of aortic aneurysm.

Abdominal aortic aneurysm (AAA) can now be corrected by perfemoral introduction of a prosthetic tube graft with fixation using expandable metal stents. This technique requires a satisfactory iliac system, through which the graft can reach its destination, and suitable lengths of non-aneurysmal aorta below the renal arteries and above the aortic bifurcation for stent attachment. The feasibility for placement of endovascular grafts was assessed in 44 consecutive patients admitted for transabdominal AAA repair. The proximal and distal aneurysmal necks and the iliac arteries were assessed before operation by colour flow Doppler ultrasonography (duplex scanning), computed tomography and intravenous digital subtraction angiography, using intraoperative measurements as the 'gold standard'. At operation 32 of 44 patients had a suitable proximal neck and five of 44 a suitable distal neck for endovascular grafting. Duplex scanning was the most accurate modality for preoperative assessment of the aneurysm necks. According to this technique 32 of 44 patients had a satisfactory iliac system for introduction of an endovascular graft. Overall only four of 44 patients were considered suitable for endovascular correction of AAA using a tube graft-stent combination.

Aged

Microvascular disease and anastomotic dehiscence in the colon.

Platelet-derived serotonin released in response to tissue manipulation during surgery may contribute to mesenteric arterial vasospasm leading to postoperative anastomotic leakage after colorectal resection. Organ bath experiments were used to demonstrate the efficacy of naftidrofuryl fumarate (NFT) to oppose serotonin-induced vasoconstriction of human mesenteric arteries. Cumulative dose-response curves were derived with and without NFT at 10(-9) and 10(-6) mol/l concentrations. The difference in maximal contractility between the three sets of curves (n = 8 for each) was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured by calculating the concentration for half-maximal response; differences were again significant (P < 0.0001). NFT reduced serotonin-induced contractility in a dose-dependent fashion in rings of human mesenteric arteries in vitro. This suggests a possible role for NFT in reducing mesenteric vasospasm in colorectal surgery.

Anastomosis, Surgical

In vitro evaluation of endovascular stents to assess suitability for endovascular graft fixation.

OBJECTIVE: To compare and ascertain the suitability for endovascular aortic graft fixation of the Palmaz stent, the Strecker stent, the modified Gianturco-Z stent, the Wallstent and a new stent made of the shape memory alloy nitinol. DESIGN, SETTING AND MATERIALS: In vitro studies using a simple tensiometer to assess the forces required to distract each stent from porcine aorta; and using a high-pressure, pulsatile-flow pump to measure flow rates required to dislodge stents holding grafts within porcine aortas, with assessment using endovascular ultrasound. RESULTS: The Palmaz, the modified Gianturco-Z and the nitinol stents resisted significantly greater distraction forces than the Wallstent, but endovascular ultrasound examination revealed that the modified Gianturco-Z stent was seen to move away from the aortic wall at high flow rates precluding adequate fixation. The Strecker stent could not be assessed using these techniques. CONCLUSIONS: A nitinol stent may be suitable for aortic graft fixation, has characteristics similar to the Palmaz stent and has shape memory effect which may overcome the difficulties of introduction of wider diameter stents through narrow arteries.

Alloys

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

Fluctuations in the secretion of pancreatic enzymes between consecutive doses of octreotide: implications for the management of fistulae.

OBJECTIVE: To determine whether variations in pancreatic enzyme secretion between consecutive subcutaneous administrations of octreotide explain why octreotide takes longer than somatostatin to facilitate the closure of gastrointestinal fistulae. METHODS: Pancreatic enzyme secretion was studied over a 3-day period in a patient with a catheter left in the pancreatic duct postoperatively. On days 1 and 3 the patient did not receive octreotide (control days) but on day 2 he received subcutaneous octreotide 100 micrograms every 8 h. Pancreatic juice was collected at 2-h intervals over the 3-day period. RESULTS: On the day of octreotide treatment, the patient's pancreatic secretory volume and protein output were significantly reduced (P < 0.001, Mann-Whitney U-test) compared with the 2 control days. The pancreatic secretory volume decreased markedly after the first injection of octreotide and remained low for the duration of the treatment period. The enzyme concentration of the pancreatic juice was also markedly reduced after the first injection of octreotide. However, approximately 4h after each octreotide injection the protein concentration of the pancreatic juice began to rise progressively, peaking approximately 6h after each administration of the analogue. CONCLUSION: Subcutaneous administration of octreotide produces a sustained decrease in the volume of pancreatic juice secreted, but enzyme secretion rises progressively between consecutive administrations of the analogue. The net effect is therefore the production of low volumes of pancreatic juice with a high enzyme concentration between consecutive injections of octreotide, which may delay the healing of the fistula tract. This may explain why longer treatment periods are required to achieve fistula closure with octreotide than with somatostatin, particularly in the case of pancreatic fistulae.

Humans

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