Search PubMed⌕ Search

Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

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

Thrombolysis in high risk patients.

The advent of intra-arterially administered thrombolytic agents of minimal antigenicity, together with small gauge good torque control catheters, enables thrombolysis to be used in patients that may previously have been deemed unsuitable for thrombolytic therapy. Thrombolysis may be used even in the presence of factors formerly and empirically considered to be contra-indications. The continued use of thrombolytic agent may also be warranted despite iatrogenic complications such as vessel wall perforation, particularly if the alternative is major amputation. We report on a series of eight patients in whom intra-arterial tissue plasminogen activator was used despite either recent vascular surgery, or iatrogenic vessel perforation. Suggestions for the use of thrombolysis in high risk patients and following iatrogenic complications are discussed.

Aged↗
PubMed1992

Evidence that sensitivity to cyclosporine is influenced by the HLA-DR phenotype of kidney graft recipients.

Clinical as well as experimental studies have shown a great interindividual variability in the immunosuppressive efficacy of CsA. Evaluating previous in vitro findings of a correlation between sensitivity of alloresponsiveness to CsA and the HLA-DR phenotype CsA levels were compared in kidney transplant recipients with and without rejections during the early posttransplant period and tested for a possible relationship to the HLA-DR phenotype of the recipient. In patients treated with CsA and prednisolone only, rejection frequency was significantly higher in HLA-DRw6 positive than in DRw6 negative graft recipients (77% vs. 53%, P = 0.045). In the DRw6 positive group incidence of rejection was independent of CsA blood levels, whereas in DRw6 negative patients frequency of rejection episodes decreased as a function of increasing CsA levels. Therefore the relative risk in developing graft rejection continuously increased in HLA-DRw6 positive patients. In HLA-DR2 positive graft recipients, however, a decrease in the relative risk could be observed with increasing CsA levels. Within patients with bioptically verified rejection episodes HLA-DR2 positive recipients had significantly lower CsA levels than DR2 negative patients (P = 0.01). In other HLA-DR phenotypes no association with CsA blood levels could be assessed. Also no statistically significant difference could be found in nonrejecting patients. These clinical findings demonstrate an association of sensitivity to immunosuppressive treatment and the HLA-DR phenotype of the graft recipient. Our results would indicate a very low CsA sensitivity of HLA-DRw6 positive graft recipients and thus might offer an explanation for previous findings about an increase in the incidence of rejection reported on those patients.

Adult↗
PubMed1992

The effect of cold storage of rat thoracic aortic rings in organ preservation solutions--a study of receptor-linked vascular prostacyclin synthesis.

An important aspect of organ preservation is the maintenance of intrinsic dilator and antithrombotic mechanisms of blood vessels. Blood vessels synthesize prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet adhesion and aggregation. PGI2 synthesis is controlled by complex mechanisms including adrenoceptor-linked calcium influx and protein kinase C. Since organ preservation solutions may influence these mechanisms, we investigated the effect on in vitro PGI2 synthesis of cold storage of rat aortic rings in lactobionate-raffinose solution (LRS) and hypertonic citrate kidney preservation solution (KPS) on in vitro PGI2 synthesis. Acute incubation of aortic tissue in both preservation solutions at 37 degrees C (compared with minimal essential medium) completely inhibited PGI2 synthesis when stimulated with noradrenaline (NA), phorbol ester (a protein kinase C activator), NaF (a G protein activator), or A23187. Following storage of aortic rings at 4 degrees C (for up to 72 hr) in LRS and KPS, subsequent washing and incubation in MEM, PGI2 synthesis was initially markedly enhanced in response to NA when compared with tissues stored in MEM. These enhanced responses disappeared, and PGI2 synthesis returned to normal following 1 hr incubation of tissues in MEM at 37 degrees C. These data demonstrate that cold storage in preservation fluids exerts minimal deleterious effects, not only on PGI2 synthesis, but possibly on other key processes (calcium homeostasis, protein kinase C activity) in blood vessels.

Adenosine↗
PubMed1992

Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis.

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗