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Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 37 records · Page 2Linked to original sources

Use of the hepatic arterial circulation for renal revascularisation.

Renal artery stenosis is increasingly being diagnosed as a cause of hypertension and renal impairment. Surgical intervention can restore function and improve hypertension in selected cases. Over a 42 month period, 12 patients with atherosclerotic renovascular disease underwent surgical revascularisation using the hepatic arterial circulation. All had disease of both renal arteries and 11 had some degree of renal impairment, with five requiring dialysis before operation. There were two deaths within 30 days of operation, eight patients had improved renal function after operation and three of the patients previously on dialysis became dialysis free. The hepatorenal method of renal revascularisation is described and its advantages discussed.

Aged

Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia.

Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase.

Acute Disease

Seeding of human microvascular endothelial cells onto polytetrafluoroethylene graft material.

Microvascular endothelial cells from human omental samples were isolated and grown. Adhesion to polytetrafluoroethylene vascular graft material was then studied using scanning electron microscopy and adhesion of cells labelled with indium-111. Grafts coated with fibronectin and type I collagen were found to promote the best adhesion of cells at times up to 90 min. A coating of blood clot matrix was less effective but still resulted in a threefold increase in cell adhesion compared with controls.

Blood Vessel Prosthesis

Intraoperative course and prognostic significance of endotoxin, tumor necrosis factor-alpha and interleukin-6 in liver transplant recipients.

Early events in reaction of the host immune system to an allograft were studied by intraoperative measurements of endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in human liver transplantation. Blood samples were collected prior to operation, before clamping of the liver vessels, at the beginning and end of the anhepatic phase, and 5 and 30 min after recirculation. Diagnosis of rejection and infection in the graft recipients was established by assessment of spontaneous blastogenesis and T-lymphocyte subpopulations in addition to clinical symptoms and results from biopsies and blood chemistry. Of the 27 unmatched liver transplantations included in this study, 8 patients had infections in the first two postoperative weeks and 6 patients showed rejection of their grafts under antithymocyte globulin immunoprophylaxis. Endotoxin was transiently elevated in plasma in the anhepatic phase (2-fold in comparison to normal values) as expected for an accumulation of intestine-derived endotoxin during clamping of liver vessels, but no correlation was found with TNF-alpha levels and specific post-transplant complications. All patients with rejections had high plasma levels of TNF-alpha immediately after recirculation (mean value 240 pg TNF-alpha/ml), in contrast to low TNF-alpha levels in graft recipients without complications or infections. These results indicate that the initiation of rejection in liver transplantation is associated with increased plasma concentrations of TNF-alpha. The measured TNF-alpha concentrations are adequate to promote the binding of lymphocytes to allograft endothelial tissue and/or to induce expression of MHC antigens in the graft. Subsequent viral or bacterial infections were preceded by high intraoperative plasma concentrations of interleukin-6 (mean value 1400 pg IL-6/ml). The correlations of rejection with high intraoperative TNF-alpha levels and of infection with those of IL-6 are statistically significant in Wilcoxon tests for the direct measurements and in Fisher's exact tests for positive test values, with limits of 90 pg/ml for TNF-alpha and 800 pg/ml for IL-6.

Adult

Comparison of prostanoid synthesis in cultured human vascular endothelial cells derived from omentum and umbilical vein.

Endothelial seeding of vascular grafts may reduce thrombogenicity and significantly improve graft patency. For clinical studies endothelial cells derived from human omentum may be the ideal source of cells as they are obtainable in large numbers. This study was designed to assess their ability to produce the antithrombogenic substance prostacyclin (PGI2). Human omental microvascular endothelial cells (HOTMECs) were grown and their ability to produce prostacyclin (PGI2), PGE2, PGF2 alpha and thromboxane A2 (TXA2) in response to a range of agonists was measured by radioimmunoassay. Control experiments were performed using human umbilical vein endothelial cells (HUVECs). Both HUVECs and HOTMECs synthesised similar quantities of PGI2 basally and both increased production after adding A23187 (calcium ionophore), arachidonic acid, sodium fluoride and phorbol ester. In contrast, both thrombin and histamine were potent stimulators of PGI2 release in HUVECs but were without effect on HOTMECs. In both cell types serotonin, carbachol and noradrenaline were without effect. The pattern of release of PGE2, PGF2 alpha and TXA2 were identical to those of PGI2 in both cell types but the quantities released were lower. These results show that HOTMECs can produce the antithrombogenic agent PGI2 in significant quantities and that they do so by mechanisms similar to those of large vessel endothelium. This supports the proposal that they would be a suitable cell source for vascular graft seeding.

Cells, Cultured

Cryptosporidiosis in the Isle of Thanet; an outbreak associated with local drinking water.

An outbreak of cryptosporidiosis occurred in the Isle of Thanet during December 1990 and January 1991. A total of 47 cases ranging in age from 2 months to 85 years were identified in residents from the Margate, Broadstairs and Ramsgate areas, with dates of onset of illness from 3 December to 14 January. A case-control study demonstrated a strong statistical association between illness and the consumption of unboiled tap water from a particular source, with evidence of a dose-response relationship. Although no cryptosporidial oocysts were identified in samples of untreated or treated water taken during the investigation, the results were consistent with the view that the source of infection was treated river water which was used to supplement borehole water.

Adolescent

The use of captopril-DTPA scanning in the diagnosis of atherosclerotic renal artery stenosis in patients with impaired renal function.

We have analyzed our use of captopril-diethylene-triaminepentaacetic acid (DTPA) scanning in patients presenting to the Royal Free Hospital predominantly with renal impairment. The sensitivity was found to be as good in patients with bilateral disease or disease of a single kidney as in patients with unilateral disease. On a number of occasions, though, the scan suggested unilateral disease when bilateral disease existed. There were, however, a large number of patients for whom captopril-DTPA scanning was not performed because of severe renal impairment or the possibility of renal artery stenosis in a single functioning kidney.

Aged

Intraoperative estimation of endotoxin, TNF alpha, and IL-6 in orthotopic liver transplantation and their relation to rejection and postoperative infection.

The course of endotoxemia, TNF alpha, and IL-6 during orthotopic liver transplantation was studied in 28 transplantations performed in 27 patients to evaluate their impact on early postoperative rejection and infection. The preoperative levels of endotoxin, TNF alpha, and IL-6 were not different in patients who did or did not develop postoperative rejection and/or infection within the first 10 postoperative days. At the end of surgery, TNF alpha levels increased in patients who developed rejection (median 100 pg/ml vs. 11.5 pg/ml, P = 0.004). A TNF alpha level of greater than 100 pg/ml at the end of transplantation predicted rejection in 82% of the patients. During surgery, IL-6 levels increased significantly in patients with subsequent postoperative infection, reaching significance after revascularization of the graft (median 975 pg/ml vs. 185 pg/ml, P = 0.006). An IL-6 cutoff level of 800 pg/ml predicted postoperative infection in 75% of the patients. Endotoxins were elevated intraoperatively in patients with postoperative infection, but the difference did not reach significance. There was no prognostic relevance with respect to the intraoperative values of TNF alpha and infection or IL-6 values and rejection. An intraoperative elevation of TNF alpha seems to precede early postoperative rejection, and highly increased IL-6 may be a predictor of subsequent infection in human liver transplantation.

Adult