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Biomedical subjects

G H Neild

Publications and source records attributed to G H Neild.

At least 109 records · Page 6Linked to original sources
PubMed1988

Platelet function and the bleeding time in progressive renal failure.

Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe renal failure (greater than 600 mumol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p less than 0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.

Bleeding Time↗
PubMed1988

Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients.

Evidence for chronic in vivo platelet activation and hyperaggregability has been assessed in 21 renal allograft recipients. All patients received long term immunosuppression with cyclosporin (CS) and low dose prednisolone and were studied serially for 1 year post-transplantation. Spontaneous platelet aggregation in PRP was observed on 10 occasions in 5 patients. Platelet aggregation responses in PRP to low doses of ADP (0.5 and 1.0 microM) were significantly increased up to 1 year post-transplantation (p less than 0.02-less than 0.002). Total platelet nucleotide (ATP and ADP) content and release to 20 micrograms/ml of collagen were significantly decreased for 2 months post-transplantation, indicative of in vivo platelet activation (p less than 0.05-less than 0.002), and plasma PF4 levels were increased up to 1 year post-transplantation suggesting continued platelet activation of a lesser degree. Platelet sensitivity to the prostacyclin analogue Iloprost decreased after 1 month (p less than 0.05) and this persisted up to 1 year (p less than 0.01) compared with sensitivity at 1 week post-transplantation. These prothrombotic changes persisted when trough whole blood CS levels were within the therapeutic range and plasma creatinine levels were approaching or were in the normal range. These data indicate that CS-treated renal allograft recipients exhibit chronic platelet hyperactivity.

Adenine Nucleotides↗
PubMed1988

Failure of cyclosporine-treated renal allograft recipients to increase glomerular filtration rate following an amino acid infusion.

Renal allograft recipients treated with cyclosporine (CsA) have increased renal vascular resistance that falls when CsA is stopped. With the aim of identifying whether CsA-treated patients with excellent renal function also have an alteration in renal vascular tone and to investigate which vessels are affected, we have studied the response of GFR and effective renal plasma flow (ERPF) to an infusion of an amino acid solution in a group of 9 CsA-treated renal transplant recipients with a normal plasma creatinine concentration (104 +/- 3.8 mumol/L [mean +/- SEM]). A similar group of 9 azathioprine-treated patients with good renal function (91 +/- 3.6 mumol/L) were used as controls. The azathioprine group had significant increases in both GFR (22%, P less than 0.05) and ERPF (19%, P less than 0.05) following a protein load, whereas there was no increase in either function in the CsA group. Amino acid infusions increase GFR and ERPF in normal kidneys--at least in part by producing afferent glomerular arteriolar dilatation. The difference we found between the two groups indicates a direct effect of cyclosporine on intrarenal vascular tone, even when renal function is considered to be normal.

Adult↗
PubMed1988

Abnormal blood rheology in progressive renal failure: a factor in non-immune glomerular injury?

Chronic renal insufficiency progresses by a final common pathway of glomerular damage characterised by microvascular injury and glomerulosclerosis. In order to investigate the possible role of blood rheology in this process, rheological indices were compared between healthy controls and a group of patients with progressive renal failure due to renal diseases that were not considered to be immunologically mediated. Plasma viscosity was significantly increased in the renal insufficiency group (P less than 0.005), and correlated with raised plasma concentrations of fibrinogen (r = 0.63; P less than 0.005). Whole-blood viscosity corrected to a standard haematocrit of 0.45 was also raised. A weak but significant correlation was seen between plasma viscosity and 24-h urinary protein excretion (r = 0.50; P less than 0.005). Our data show that in chronic renal insufficiency, rheology is abnormal. Proteinuria correlates with plasma viscosity, which is consistent with the hypothesis that raised plasma viscosity leads to an increase in glomerular capillary pressure and thence glomerular permeability. Correction of rheological abnormalities might help to preserve kidney function and reduce proteinuria in these patients.

Adolescent↗
PubMed1987

Histopathological changes in cyclosporin-treated renal allografts biopsied at one and twelve months.

Forty-four renal allograft recipients were biopsied routinely one month and one year after transplantation. All patients received cyclosporin and prednisolone. Fifteen patients had at least one rejection episode, while 29 patients never underwent rejection. At one year there were no specific histological features that enabled these two groups to be distinguished. Between one month and one year, interstitial cellular infiltrate and vascular pathology regressed, and renal function steadily improved. Interstitial fibrosis, however, was either unchanged or mildly increased in all patients. There was no correlation between the amount of interstitial fibrosis at one year and either the total dose of cyclosporin or the mean concentration during the first 3 months. Our results suggest that trough, whole blood cyclosporin concentrations, at the upper level of the therapeutic range (800-200 ng/ml), may be safely tolerated during the first 3 months, with little evidence of chronic damage at one year. At one year maintenance doses of cyclosporin can be achieved that are associated with almost normal plasma creatinine concentrations and minimal tubular atrophy and interstitial fibrosis. We expect that such doses may be continued indefinitely.

Adolescent↗
PubMed1986

Increased factor VIII as an index of vascular injury in cyclosporine nephrotoxicity.

Very high plasma concentrations of factor-VIII-related antigen (RAG) (VIII-RAG) were found in renal allograft recipients during periods of nephrotoxicity induced by cyclosporine. In eight recipients, who were investigated at weekly intervals, levels of factor-VIII-RAG fell toward normal as the dose of cyclosporine was reduced. Plasma levels of C-reactive protein, an acute phase reactant protein, were never raised in these recipients. These findings are further evidence that toxic doses of cyclosporine are associated with vascular injury.

Antigens↗
PubMed1986

Morphological differentiation between rejection and cyclosporin nephrotoxicity in renal allografts.

In a prospective study of renal dysfunction in 60 consecutive allograft recipients treated with cyclosporin and prednisolone routine renal biopsies at one week and one month after transplantation, as well as for all episodes of renal dysfunction, were performed. The one year graft survival of this group was 88%. In a retrospective clinical analysis of these patients 35 episodes of dysfunction due to rejection, defined by a response to antirejection treatment alone, and 30 episodes due to cyclosporin nephrotoxicity, defined by a response to reduction in cyclosporin dose alone, were identified. The morphological findings from these biopsies were compared with 20 samples from routine biopsies taken from patients with stable renal function. All patients diagnosed as having rejection had a diffuse, interstitial mononuclear cell infiltrate (32 of 35) or arteritis (19 of 35), or both. In contrast, focal mononuclear cell infiltrates were common in both patients with nephrotoxicity and those with stable function (17 of 30 and 14 of 20, respectively). There were no important differences between biopsies from those with nephrotoxicity and those with stable function, except that arteriolar hyalinosis was considerably more common in the nephrotoxic patients than in those with stable function. Many patients with stable function were, in retrospect, in a state of stable mild nephrotoxicity. In our experience rejection should only be diagnosed when there is at least a diffuse interstitial infiltrate or an arteritis. Focal mononuclear cell infiltrates do not denote rejection. The development of arteriolar lesions in the absence of rejection is indicative of nephrotoxicity.

Adolescent↗
PubMed1986

Effect of cyclosporine on proteinuria in chronic serum sickness in rats.

A model of chronic serum sickness (CSS) was established in Wistar rats. Rats were given 2 mg of bovine serum albumin (BSA) i.p. five days/week. A group of six male rats were bred which developed albuminuria after three weeks. Rat albumin was measured by radial immuno-diffusion. Albuminuria increased gradually over the first 80 days. On days 87 and 88 rats were given 25 mg/kg methylprednisolone (MP) i.p. Albuminuria increased from 1.1 mg/ml to 1.7 mg/ml. After proteinuria had returned to pre-treatment values, MP was given again with the same result. From day 115 rats were given 25 mg/kg of CYA i.p. for three consecutive days. Albuminuria fell from 0.85 mg/ml to 0.28 mg/ml, and for the first time rats developed microscopic haematuria. After five days proteinuria returned to former levels but then rose to higher levels. On day 146 rats were given CYA and albuminuria fell from 1.7 to 0.45 mg/ml. On day 150 the renal histology was examined by light microscopy and the glomeruli showed no significant abnormalities.

Animals↗
PubMed1985

Differentiation between allograft rejection and cyclosporin nephrotoxicity in renal-transplant recipients.

In a retrospective study of 60 renal-transplant patients immunosuppressed with cyclosporin no specific clinical features differentiated allograft dysfunction responsive to anti-rejection therapy from dysfunction responsive to reduction in cyclosporin dosage. Histologically, allograft dysfunction responsive to anti-rejection therapy was strongly associated with diffuse interstitial infiltration by mononuclear cells, oedema, and haemorrhage, vascular endothelial-cell proliferation, and infiltration of arterial walls by mononuclear cells. Arteriolar medial hypertrophy and hyalinosis were more commonly found in biopsy specimens from allografts with dysfunction responsive to reduction in cyclosporin dose than in those with dysfunction responsive to anti-rejection therapy and those with stable or improving function. Whole-blood cyclosporin concentrations were significantly lower in patients with dysfunction reversed by anti-rejection therapy than in those with dysfunction reversed by reduction in cyclosporin dose or in those with stable function. There was, however, considerable overlap between these groups, so that individual cyclosporin measurements were of little diagnostic value.

Adolescent↗