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T Horsburgh

Publications and source records attributed to T Horsburgh.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular cells.

The adverse effects of acute renal ischemia are partly mediated through an infiltration of inflammatory cells into the tubulointerstitium. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by resident renal cells (endothelial cells and tubular cells) may facilitate this process. We investigated whether hypoxia stimulates the expression of ICAM-1 by cultured human proximal tubular cells (HPTC). Hypoxic culture conditions (PO2 < 4 kPa) stimulated the expression of ICAM-1 by HPTC in a time-dependent manner (P < 0.0001) as demonstrated by quantitative flow cytometry analysis. Quantitative PCR demonstrated an increase in ICAM-1 transcription. Re-oxygenation of tubular cells did not increase ICAM-1 expression further. TNF alpha concentration in culture supernatants increased with hypoxia, but blocking experiments demonstrated that TNF alpha was not implicated in hypoxia-induced expression of ICAM-1. Furthermore, the cytokines IL-6 and IL-1 beta were not involved, but the effect of hypoxia was blocked by PDTC, an antioxidant that may inhibit the activation of the transcription factor NF-kappa B. These data demonstrate that hypoxia is a stimulus that induces the synthesis and expression of the adhesion molecule ICAM-1, presumably via the activation of NF-kappa B.

Antioxidants↗
PubMed1997

Urological complications in renal transplantation: impact of a change of technique.

OBJECTIVE: To determine whether the change from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis in renal transplantation has altered the incidence of urological complications. PATIENTS AND METHODS: Data were retrieved from a prospective computerized database and by case-note review on 248 consecutive renal transplants performed between January 1990 and June 1996. The characteristics of the donor. recipient and organ were noted, together with the technique used for the vesicoureteric anastomosis and the occurrence of major and minor urological complications. RESULTS: The Leadbetter-Politano technique was used in 140 transplants and the stented extravesical technique in 108. There were no significant differences in the donor, recipient or organ characteristics between the groups. The stented extravesical technique was associated with a significantly lower rate of major complications (< 2%) and clinically significant haematuria than with the Leadbetter-Politano technique. CONCLUSION: Changing from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis has been a major factor in reducing the incidence of urological complications in our transplant practice.

Adolescent↗
PubMed1996

Evaluation of the flow cytometric crossmatch. Preliminary results of a multicenter study.

The flow cytometric crossmatch is a technique that is increasingly being used by clinical transplant laboratories. In this multicenter study by the British Society for Histocompatibility and Immunogenetics Flow Cytometry Group, a series of crossmatches were carried out to determine whether different centers obtained same results when performing the same crossmatch. There was greater than 80% agreement among participating laboratories on the results of 35/54 tests. There was no clear agreement in the remaining 20 cases. Quantitative analysis, estimating the number of cell-bound fluorescein molecules, demonstrated that differences in the criteria used by each center to define a positive crossmatch were responsible for some discordant results. When applied, definition of positivity based on the molecules of fluorescein increased concordance from 57.5% to 81.4%.l. These results suggest that a criterion for the interpretation of results based on quantitative analysis of bound antibody may be more reliable than methods in current routine use.

Flow Cytometry↗
PubMed1996

The relative influence of delayed graft function and acute rejection on renal transplant survival.

Three hundred and eight cadaveric renal transplants were analysed to establish the effects of acute rejection in the first 90 days and delayed graft function (DGF) on graft outcome. There were 120 patients (39%) with no DGF and no rejection (group 1), 101 patients (33%) with rejection but no DGF (group 2), 41 patients (13%) with DGF but no rejection (group 3) and 46 patients (15%) with both rejection and DGF (group 4). The actuarial 4-year graft survival rates for groups 1,2,3 and 4 were 78.3%, 65.4%, 60.1% and 40.4%, respectively. The acute rejection rate was 101/221 (46%) in patients with initial graft function compared with 46/87 (53%) for those with DGF (chi 2 = 1.02, P = 0.31). Cox stepwise logistic regression analysis demonstrated that DGF was a more powerful predictive factor for poor graft survival (P = 0.001) than acute rejection occurring in the first 90 days post-transplant (P = 0.034). Further efforts at improving graft outcome should concentrate on reducing the incidence of DGF.

Acute Disease↗
PubMed1996

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.

Administration, Oral↗
PubMed1995

Lack of correlation of soluble E-selectin level with renal transplant rejection.

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.

Biomarkers↗
PubMed1995

UK studies on suramin therapy in hormone resistant prostate cancer.

New insights regarding the biology of hormone resistant CaP have shown that major growth factors other than testosterone are responsible for cellular proliferation of androgen resistant prostate cancer cells. In vitro studies have confirmed the efficacy of growth factor inhibitors such as suramin in reducing cellular proliferation of androgen dependent LNCaP and independent PC-3 CaP cell lines as well as CaP cells obtained by primary culture. Initial clinical trials using high dose suramin (peak serum concentration 250-300 micrograms/ml) as monotherapy in patients with hormone resistant CaP have shown some promise, but the duration of response to therapy has been short lived and suramin toxicity is a problem. To minimize toxicity without reducing anti-tumour activity, studies evaluating its use in combination with other cytotoxic drugs are attractive in CaP. Suramin and doxorubicin, tumour necrosis factor and EMP have shown synergy in vitro. However, in a phase II clinical trial using combination therapy with low dose suramin (140 micrograms/ml) and mitomycin C in 32 patients, there was one complete response and six partial responses, and in 15 patients, the disease had stabilized. The median time to treatment failure was 103 days, and the median survival was 209 days. This regimen caused significant toxicities. The present study has shown that the combination of EMP 280 mg twice a day and suramin 1 g weekly infusions for 6 weeks, compared to EMP 280 mg alone, showed a statistically significant difference in the rate of depression of PSA levels after 3 and 6 months of treatment (p < 0.01) and a statistically significant reduction in bone pain and requirement for analgesics in patients on combination therapy-100% compared to 0% for patients on EMP alone.

Aged↗
PubMed1994

The importance of E-selectin as a marker for renal transplant rejection.

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.

Biomarkers↗
PubMed1993

The relevance of anti-A549 antibody in adult renal transplantation.

Sera from 228 individuals were examined for cytotoxic antibodies against the cultured lung epithelial cell line A549. All samples were screened by the conventional complement mediated cytotoxicity assay. The pattern of the anti-A549 reactivity in normal volunteers (n = 12) was 42% negative, 30% weak positive and 25% strong positive. The overall incidence of anti-A549 antibody in chronic renal failure patients (n = 84) was 7% weak positive and 7% strong positive. In 132 patients with a functioning renal allograft the frequency of anti-A549 reactivity increased (19% weak positive, 27% strong positive) and was comparable to that found in normal controls. The presence of anti-A549 antibody did not correlate with panel antibody allosensitization, cytomegalovirus status, age, mode of dialysis, rejection episodes, or with subsequent graft survival. We conclude that in adult renal transplantation the presence of anti-A549 antibody is not a contra-indication to transplantation.

Adolescent↗
PubMed1993

Glomerular perfusion in renal allograft biopsies.

In the commonest causes of impaired renal transplant function there is reduced renal and glomerular perfusion. We investigated the possibility of identifying this phenomenon in renal transplant biopsies, by the crude but simple method of counting the mean numbers of glomerular capillary loops which contained erythrocytes. In cyclosporin toxicity, acute tubular necrosis and in acute cellular rejection there was a considerable reduction in the numbers of erythrocyte-containing glomerular capillaries. The separation of the acute tubular necrosis group from normal was almost complete. This feature is therefore not specific but appears to correlate well with states of impaired glomerular perfusion. We suggest that a simple assessment of glomerular erythrocyte 'load' forms a useful part of the histological examination of renal transplant biopsies.

Biopsy↗
PubMed1992

Nifedipine improves immediate, and 6- and 12-month graft function in cyclosporin A (CyA) treated renal allograft recipients.

To investigate the effect of oral nifedipine, a calcium channel blocker known not to modify cyclosporin A (CyA) pharmacokinetics, on immediate transplant function and CyA nephrotoxicity, 68 adult renal transplant recipients were pre-operatively randomized to one of three regimes: A (high-dose CyA, initial dose 17 mg/kg per day, maintenance dose 7 mg/kg per day); B (regime A plus oral nifedipine); C low-dose CyA, initial dose 10 mg/kg per day, maintenance 4 mg/kg per day plus azathioprine 1 mg/kg per day). All three groups received identical steroid regimes. Calcium channel blockers of all types were avoided in groups A and C. Delayed graft function (dialysis dependence by day 4) was seen least frequently in group B (P < 0.02). Group B had improved graft function at 6 months compared with group A, identified by differences in serum creatinine (P < 0.05), GFR (P < 0.01) and ERPF (P < 0.05). Similar differences in serum creatinine (P < 0.05) and GFR (P < 0.05) were also identified at 12 months. Group C also had better 6- and 12-month GFR values than group A (P < 0.05 each). The three groups did not differ in donor or recipient age, HLA matching, ischaemic or anastomosis times, frequency of early rejection or whole-blood CyA levels. These results indicate that nifedipine significantly improves immediate and medium-term graft function.

Adult↗