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Edward Kingdon

Publications and source records attributed to Edward Kingdon.

10 recordsLinked to original sources
PubMed2005

The isoprostane 8-iso-PGF2alpha suppresses monocyte adhesion to human microvascular endothelial cells via two independent mechanisms.

Isoprostanes, produced in vivo by non-enzymatic free-radical-induced lipid peroxidation, are markers of oxidative stress. Elevated serum and urine levels of 8-iso-PGF2alpha have been reported in a variety of diseases, many of which are characterized by early perivascular inflammatory infiltrates. It has been suggested that, in addition to being markers of oxidative stress, isoprostanes may have pathogenic functions. In this study, we investigated the potential role of 8-iso-PGF2alpha in inflammation, focusing on its effects on adhesion of monocytes to microvascular endothelial cells, an early event in the inflammatory response. In monocyte adhesion assays, 8-iso-PGF2alpha (>10(-8) M) suppressed both basal and TNF-alpha-induced monocyte adhesion to quiescent or proliferating human dermal (HMEC) and rat renal microvascular endothelial cells. In contrast, 8-iso-PGF2alpha stimulated monocyte adhesion to human umbilical vein endothelial cells (HUVEC) as also reported by others. 8-Iso-PGF2alpha had no effect on the viability (Trypan Blue exclusion) of U937 monocytes or HMEC. 8-Iso-PGF2alpha also had no effect on HMEC surface expression of ICAM-1 or VCAM-1. Exposure of HMEC to 8-iso-PGF2alpha for 1-2 h was sufficient to reduce monocyte adhesion to the cell surface, and this effect was independent of de novo protein synthesis by HMEC. The effect of 8-iso-PGF2alpha was mimicked by a thromboxane receptor (TP) agonist (U46619) and blocked by a TP antagonist (SQ29548), indicating a TP-mediated process. Signal transduction pathway inhibitors (SB203580, curcumin, and PD98059) implicated p38 and JNK, but not ERK, in 8-iso-PGF2alpha-induced suppression of monocyte adhesion. In addition to a direct effect, conditioned medium (CM) transfer experiments suggest that 8-iso-PGF2alpha induces a secondary mediator, which also suppresses monocyte adhesion but via an alternative mechanism initiated between 3-4 h, which is TP-independent, requires new protein synthesis, and is primarily dependent on activation of p38. The data show that 8-iso-PGF2alpha can suppress the attachment of monocytes to HMECs via two independent pathways, indicating a potential anti-inflammatory effect of 8-iso-PGF2alpha in the microvasculature.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2004

Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids.

BACKGROUND: Treatment of adults with idiopathic membranoproliferative glomerulonephritis (IMPGN) is often unrewarding with approximately 60% of patients progressing to end-stage renal failure within 10 years. Although children with IMPGN may respond to steroid therapy, there is no significant benefit to treating adult IMPGN patients with immunosuppression. METHODS: Outcome measures in five patients with IMPGN who were treated with oral prednisolone and mycophenolate mofetil (MMF) (treatment group) were compared with six patients with IMPGN who did not receive immunosuppression (control group). RESULTS: There was no significant difference between either group in baseline clinical characteristics or systolic and diastolic blood pressure during observation. In the treatment group, there was a significant reduction in proteinuria from a baseline of 5.09 to 1.97 g/24 h (P = 0.003) at 6 months, 1.96 g/24 h (P = 0.003) at 12 months and 2.59 g/24 h (P = 0.015) at 18 months. There was no significant change in proteinuria over 18 months in the control group. Serum creatinine concentration and creatinine clearance did not change significantly over 18 months in the treatment group. In the control group, there were significant changes in serum creatinine and creatinine clearance over 18 months [baseline 103 to 159 micromol/l (P = 0.004) and baseline 108 to 67 ml/min (P > 0.001), respectively] when compared to baseline, although the differences were not significant when the two groups were compared directly. CONCLUSIONS: This preliminary study suggests that in the short term, the combination of MMF and prednisolone can significantly reduce proteinuria and may preserve renal function in patients with IMPGN.

Adrenal Cortex Hormones↗
PubMed2004

Transjugular kidney biopsy.

BACKGROUND: Most previous studies demonstrating the feasibility of transjugular kidney biopsy have used a modified Colapinto aspiration biopsy needle. We present 25 high-risk patients, with contraindications to percutaneous renal biopsy, who underwent transjugular kidney biopsy using a transvenous side-cut needle. This technique is easier to learn and can be performed by an interventional radiologist with transjugular liver biopsy experience and equipment. The needle is designed for optimal cortical sampling but has a high incidence of capsular perforation. Elective coil embolization was used in selected patients to reduce the risk of bleeding. METHODS: We retrospectively reviewed the indications for obtaining renal histology, based on clinical presentation, and the specific indications for transjugular biopsy. Transjugular kidney biopsy was assessed for sampling effectiveness and adequacy, the impact of histology on patient management, and technique complication rates. RESULTS: Renal tissue was obtained in 23 cases, with diagnostic biopsies in 21 of 23 (91.3%). A mean of 3.5 cores were obtained with 9.9 glomeruli per procedure for light microscopy (range, 0 to 32), 2.2 (range, 1 to 7) for electron microscopy, and adequate tissue for immunoflorescence available in 11 of 23 biopsies. Histology influenced patient management in all 23 cases. Capsular perforation was recorded in 73.9% (17 of 23) of cases with 6 undergoing elective coil embolization. Two major complications occurred, both in patients with multiple risk factors for bleeding. One required coil embolization of an arterio-calyseal system fistula. A further patient developed renal vein thrombosis 6 days after a failed transjugular kidney biopsy. CONCLUSION: Transjugular kidney biopsy provides a histological diagnosis in high-risk patients, making an important contribution to patient management.

Adult↗
PubMed2004

Acute transplant rejection induced by blood transfusion reaction to the Kidd blood group system.

Many renal transplant centres now try to avoid blood transfusion prior to renal transplantation, to avoid alloimmunization due to antibody production against donor antigens usually present on contaminating white cells. Post- or peri-operative transfusions are usually not considered to present problems, since the patient is heavily immunosuppressed. We present a patient who suffered a rare transfusion reaction, that we believe may have initiated a severe vascular rejection of a kidney transplant, probably mediated by Kidd blood group antigens.

Acute Disease↗
PubMed2003

Peroxynitrite-induced oxidation of plasma lipids is enhanced in stable hemodialysis patients.

BACKGROUND: The relationship between end-stage renal disease (ESRD), hemodialysis, and oxidative stress is controversial. To determine whether ESRD causes oxidative stress, we measured basal levels of plasma F2-isoprostanes as a marker of lipid peroxidation in vivo, and peroxynitrite-stimulated formation of F2-isoprostanes, as a marker of the oxidizibility of plasma lipids in vitro, before and after routine hemodialysis. METHODS: Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls. Plasma vitamin E concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: There was no difference in basal plasma concentrations of F2-isoprostanes in the ESRD group prior to hemodialysis, 246 +/- 20 pg/mL, compared to controls, 252 +/- 28 pg/mL, or immediately on completion of hemodialysis, 236 +/- 14 pg/mL. Incubation of control plasma with SIN-1 caused the formation of F2-isoprostanes with plasma concentrations increasing to 987 +/- 54 pg/mL at 6 hours. The formation of F2-isoprostanes stimulated by SIN-1 was markedly enhanced in the plasma obtained from patients undergoing hemodialysis at 1861 +/- 174 pg/mL, P < 0.001, and SIN-1-induced formation of F2-isoprostanes was further increased in plasma obtained immediately after hemodialysis at 2437 +/- 168 pg/mL, P < 0.001. Incubation of plasma with SIN-1 resulted in the net consumption of vitamin E. CONCLUSION: Although basal plasma F2-isoprostanes were similar in patients with ESRD compared with controls, the presence of oxidative stress in patients with ESRD was unmasked when the plasma was stressed by peroxynitrite generated from SIN-1, and this was enhanced further by hemodialysis.

Adult↗