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Biomedical subjects

G H Neild

Publications and source records attributed to G H Neild.

At least 73 records · Page 4Linked to original sources
PubMed1994

Endothelin plasma levels in hypertensive patients with vascular disease.

UNLABELLED: Physiology of endothelin: Circulating levels of immunoreactive endothelin-1 are very low, and below the level required for vaso-activity. It has a long duration of action but only 1-2 min of half-life. It is metabolized in the lungs, liver and kidney and is a profound constrictor of the pulmonary, renal, coronary and peripheral circulation. The prepro-endothelin-1 promoter contains an insulin-responsive element. Inhibitory regulators include nitric oxide and prostacyclin. Endothelin in hypertension and cardiovascular disease: In both experimental animal and human hypertension, endothelin levels are not consistently reported to be elevated. They are, however, elevated in atherosclerosis, congestive cardiac failure and renal insufficiency. Since endothelin is a sensitive marker of endothelial injury, these elevated levels may simply reflect diffuse endothelial injury. The endothelium is a crucial factor in cardiovascular disease. Three important risk factors, ageing, hypertension and hypercholesterolaemia, are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. The release of endothelin-1 appears to increase with age while sensitivity to this peptide decreases. CONCLUSIONS: Endothelin may be a useful marker of end-organ damage, for example in atherosclerosis, but its pathogenic effects in hypertension remain unclear.

Endothelins↗
PubMed1993

Inhibition of nitric oxide limits infarct size in the in situ rabbit heart.

Recent data has suggested a dual role for nitric oxide (NO) so that it can both attenuate myocardial injury during ischaemia and reperfusion as well as mediate reperfusion injury. In this study in the in situ rabbit heart, we have shown that pretreatment with intravenous NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthesis) significantly reduced infarct size following sustained coronary artery occlusion and reperfusion. L-NAME was also noted to increase myocardial lactate concentration. This study provides further evidence that protection against ischaemia-reperfusion injury can be derived from manipulation of the microcirculation.

Analysis of Variance↗
PubMed1993

The effect of recombinant human erythropoietin on cardiovascular responses to postural stress in dialysis patients.

The normal response to 45 degrees head-up tilt (decreased stroke volume and cardiac output and increased heart rate and peripheral resistance) is not seen in the majority of haemodialysis patients. This is due to both an abnormal baroreceptor reflex and increased venous tone which may be explained by a number of factors including hypoxia, acidosis and sodium retention. We have studied this response by impedance cardiography in eight chronic haemodialysis patients, both before and after 3 months of treatment with human recombinant erythropoietin. Before treatment the cardiovascular parameters were abnormal both at rest and on tilting in each patient. The change in each measurement following tilting was: stroke volume, 0.5 +/- 6%; cardiac output, 6 +/- 5%; peripheral resistance, -8 +/- 4%; and heart rate, 10 +/- 4%. After 3 months of erythropoietin (150 U/kg/week intravenously) the mean haematocrit had risen from 19.5 +/- 3% to 32.9 +/- 4% and all patients felt physically fitter. Impedance showed no change in the supine-indices but after tilting there was a dramatic fall in stroke volume (-26 +/- 7%) and cardiac output (-17 +/- 7%) and an increase in heart rate (15 +/- 4%) and peripheral resistance (28 +/- 10%) each moving towards the normal response. These results indicate that human recombinant erythropoietin normalizes the response to postural stress in these patients and suggest that anaemia is the principal cause of the abnormal venoconstriction seen in haemodialysis patients. The mechanisms involved warrant further investigation.

Adult↗
PubMed1993

Ureteric peristalsis studies in loin pain and haematuria syndrome: another diagnostic disappointment.

Although not a cause of progressive renal damage, loin pain and haematuria syndrome is nevertheless associated with significant morbidity. The management of pain often presents a formidable problem to urologists, physicians and general practitioners. An earlier study noted hold-up of urine in the renal pelvis and implicated this in the pathogenesis of pain. In this study we have failed to demonstrate an excess incidence of disordered urinary peristalsis in loin pain and haematuria syndrome.

Back Pain↗
PubMed1993

Endothelin-1 in the rabbit: interactions with cyclo-oxygenase and NO-synthase products.

1. Endothelin-1 infusion (5-40 pmol kg-1 min-1) in the normal anaesthetized rabbit, produced a dose-dependent increase in mean arterial blood pressure (MAP) and reduced renal blood flow (RBF) and glomerular filtration rate (GFR), when compared with an equivalent infusion of physiological saline. 2. Endothelin, 20 pmol kg-1 min-1, was also assessed in animals pretreated with either indomethacin (2 mg kg-1), methylene blue (1.6 mg kg-1 h-1) or NG-monomethyl L-arginine (L-NMMA, 10 mg kg-1 h-1). 3. The effect of endothelin on MAP and RBF was enhanced (P = 0.05 and < 0.01 respectively) by the cyclo-oxygenase inhibitor, indomethacin, without any significant change in the effect on GFR. 4. Methylene blue and L-NMMA, inhibitors of endothelium-derived relaxant factor (EDRF), enhanced the effect of endothelin on each of the parameters measured (P < 0.01). 5. Our results are consistent with endothelin having a predominant effect on pre-glomerular vascular resistance to reduce GFR. Endothelin appears to stimulate the release of vasodilator prostanoids and EDRF which oppose its effects. Thus endothelin may have an important role in the complex control of GFR in the rabbit.

Amino Acid Oxidoreductases↗
PubMed1993

Renal scintigraphy in acute scleroderma: report of three cases.

Scintigraphic findings in acute renal failure secondary to scleroderma are reported. In three patients, we have demonstrated severe reduction of renal perfusion with little or no parenchymal uptake of tracer and absent excretion. These findings are compatible with the known histological process of occlusive vasculopathy, and such scintigraphic findings at presentation may reflect a poor prognosis for renal recovery.

Acute Kidney Injury↗
PubMed1992

High resolution proton magnetic resonance spectroscopy of cyst fluids from patients with polycystic kidney disease.

High field 1H-NMR spectra of fluid collected from the cysts of six renal transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) have been measured and the major metabolite signals assigned. Quantitative NMR measurements have revealed a combination of unusual biochemical features of the cystic fluids that shows them to be distinct from both blood plasma and urine. Isoleucine, lysine, threonine and valine were present at mM concentrations, in cyst fluid and in some cases levels up to 2 orders of magnitude higher than normal plasma or urine were recorded. Mean glucose concentrations in the cyst fluids ranged from 3.4-9.6 mM and a number of organic acids and bases, including acetate, lactate, succinate, creatinine and dimethylamine were also present at high concentration and in different ratios to those found in either plasma or urine. The majority of cyst fluids examined also contained significant quantities of glycoproteins with characteristic 1H-NMR signals from N-acetyl groups of amino-sugar and sialic acid side chains which had a high degree of molecular mobility (as indicated by their relatively long T2 relaxation times, greater than 120 ms). High levels of ethanol (0.5-12.6 mM/l) were found in all fluid samples from the six transplanted patients (confirmed by conventional analysis). In general there was little variation in the 1H-NMR spectral patterns of either the intra- or interpatient cyst fluids, although the contribution of the protein macromolecules to individual spectra was lower in a few cysts. This constancy of biochemical composition probably reflects the chronic nature of the accumulation of cyst fluid and a long turnover of the cystic fluid components which has the effect of averaging composition. These findings suggest that the dynamic composition of cyst fluid from ADPKD patients is unique among the other body fluids and that the unusual composition may be related to epithelial polarity reversal of the cystic epithelium which could also contribute to the growth of the cysts.

Amino Acids↗
PubMed1992

IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells.

The elicitation of neutrophils and monocytes from the circulation into the inflamed glomerulus is a key process in the pathogenesis of proliferative glomerulonephritis. The aim of this study was to determine the factors which regulate the expression and synthesis of the monocyte specific chemotaxin, monocyte chemotactic peptide 1 (MCP-1). Mesangial cells in culture did not constitutively express MCP-1, but could be induced to express both MCP-1 mRNA and antigenic MCP-1 by either stimulation with IL-1 alpha or TNF alpha, which are also stimuli for interleukin 8 (IL-8/NAP-1) expression and release. Pre-treatment of mesangial cells with the IL-1 receptor antagonist (IL-1ra) induced dose-dependent inhibition of both the expression of MCP-1 and IL-8 mRNA as well as the release of both chemotactic peptides in response to IL-1 alpha, while the receptor antagonist had no significant effect on TNF alpha induced MCP-1 and IL-8 generation. This study demonstrates that the IL-1 receptor antagonist was four times more effective at inhibiting the IL-1 induced expression and release of IL-8 compared to that of MCP-1. These results suggest that mesangial cell-derived MCP-1 may play an important role in the recruitment of monocytes in glomerular inflammation and that an IL-1 receptor antagonist may have therapeutic potential for the treatment of glomerulonephritis.

Base Sequence↗
PubMed1992

Platelets from patients on haemodialysis show impaired responses to nitric oxide.

1. Platelets from patients on haemodialysis showed a loss of sensitivity to nitric oxide, reflected by a reduction in the ability of nitric oxide both to inhibit thrombin-induced aggregation and to increase intraplatelet cyclic GMP levels. Responses of platelets from patients on continuous ambulatory peritoneal dialysis were slightly, but not significantly, impaired. Platelets from both groups of uraemic patients showed normal sensitivity to the cyclic AMP-dependent inhibitor prostacyclin. 2. Reduced levels of cyclic GMP in response to nitric oxide in platelets from patients on haemodialysis were due to a defect in its generation, rather than to accelerated breakdown. 3. Basal levels of intra-platelet cyclic GMP were significantly increased in both patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis. 4. The activity of nitric oxide was more stable in plasma than in buffer; its survival in plasma from patients on haemodialysis was similar to that in plasma from healthy control subjects.

Adult↗
PubMed1992

Idiopathic pulmonary haemosiderosis: a form of microscopic polyarteritis?

Idiopathic pulmonary haemosiderosis remains a diagnosis of exclusion in patients who present with pulmonary alveolar haemorrhage. Systemic vasculitis developed in a patient with an eight year history of idiopathic pulmonary haemosiderosis. The diagnosis was confirmed by a rising titre of antineutrophil cytoplasmic antibodies directed against myeloperoxidase. Treatment with immunosuppressive agents resulted in complete resolution of symptoms and suppression of the antibodies. Measurement of antineutrophil cytoplasmic antibodies is recommended for all patients with pulmonary alveolar haemorrhage syndromes.

Adult↗
PubMed1991

Renal transplantation into abnormal lower urinary tract.

Because doubts remain about the safety and efficacy of renal transplantation for patients with primary urological abnormalities, we have studied the outcome of transplantation in a large group of such patients. Between 1977 and 1989, 69 renal transplants were completed in 62 patients with abnormal lower urinary tracts (29 primary vesicoureteric reflux, 13 posterior urethral valves or bladder outflow obstruction, 6 vesicoureteric tuberculosis, 5 neuropathic bladders, and 9 miscellaneous causes). Graft survival in this urological group was similar to that in 150 allograft recipients (157 grafts) with end-stage renal failure of a non-urological cause. No aetiological subgroup had poorer graft survival than the others, although patients with recurrent urinary-tract infections and a history of outflow obstruction tended to have worse graft function. 9 patients (10 transplants) had renal transplantation into a urinary diversion (8 ileal conduits, 1 rectal bladder). These patients had graft survival and renal function comparable with those of the whole urological group. We found no effect of immunosuppressive treatment (cyclosporin or azathioprine), type of kidney donor (living or cadaveric), or donor or recipient age on graft survival time or renal function. Thus, renal transplantation in patients with abnormal lower urinary tracts is safe and effective; patients with ileal conduits do well and have few substantial difficulties. Preoperative assessment of bladder emptying and urodynamics are important in these patients.

Actuarial Analysis↗
PubMed1991

Endothelium and glomerular growth.

The role of glomerular endothelium has been barely considered, let alone investigated, but this is in large part due to the extreme difficulty in isolating and growing it in culture. The glomerular capillary is part of the arterial system and is better perceived as a "hemiarteriole." The mesangium and its response to hemodynamic events in the glomerular capillary is equivalent to the smooth muscle cell wall of an arteriole. The capability of cytokines, derived from the endothelium, to act in an autocrine and paracrine manner is clearly demonstrated by angiogenesis. The glomerular endothelial cell is likely to play a crucial role in the glomerulus in health and disease.

Animals↗
PubMed1991

Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8.

Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibition of the release of extracellular IL-8, while cell-associated IL-8 and IL-8 mRNA were not significantly altered. We propose that the mesangial cell has a direct role in the initiation and propagation of inflammatory events within the glomerulus via the generation of the chemotactic cytokine IL-8.

Cells, Cultured↗