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Biomedical subjects

A M Davison

Publications and source records attributed to A M Davison.

At least 55 records · Page 3Linked to original sources
PubMed1995

Alterations of glomerular basement membrane charge and structure in diabetic nephropathy.

We examined glomerular basement membrane anionic site distribution identified by cationic gold in seven patients with insulin-dependent and four patients with non-insulin-dependent diabetes mellitus, presenting a spectrum of clinical and glomerular changes. Anionic sites were investigated by pretreatment of tissue with glycosaminoglycan-degrading enzymes prior to cationic gold staining. The distribution of chondroitin sulphate proteoglycans--a previously unrecognized glomerular basement membrane component--and type IV collagen was examined by immunoelectron microscopy to identify structural changes in the basement membrane. Findings were compared with those of non-diabetic patients showing minor proteinuria and morphologically normal glomerular basement membranes. Two patients, originally diagnosed as having diabetic nephropathy were also examined at 19 weeks and 5 years after renal transplantation. Characteristic redistribution of type IV collagen and chondroitin sulphate proteoglycans was noted in thickened glomerular basement membrane segments (> 400 nm) of diabetic patients and those with renal transplants. Extension of anionic sites deep into the glomerular basement membrane at pH 2.5, together with loss of interna sites at pH 5.8 is unique to diabetic nephropathy. Reduced charge density was apparent in some patients due to thickening of the glomerular basement membrane, although the number of anionic sites per unit length of membrane was actually increased. Thus, charge aberration in diabetic nephropathy is due to displacement rather than loss of anionic sites. Removal of more than 90% of these sites by heparitinase, confirms their association with heparan sulphate proteoglycans. Similar derangement of anionic sites in all patients with diabetic nephropathy irrespective of the degree of proteinuria, suggests that a heparan sulphate proteoglycan-related charge barrier plays a minor role in controlling permeability of the diabetic glomerular basement membrane.

Adolescent↗
PubMed1995

Quantitative reticulocyte analysis may be of benefit in monitoring erythropoietin treatment in dialysis patients.

Reticulocyte responses to low-dose erythropoietin (EPO) were monitored using automated flow cytometric analysis. Sixteen adult dialysis patients were treated with 1,000 U of recombinant human EPO (rHuEPO), subcutaneously, thrice weekly (mean dose 15.7, SD 3.7 U/kg). The reticulocyte count (baseline 31.1, SD 19.1 x 10(9)/L) increased in 14 patients in the first week, with a peak response occurring at Week 2 (mean 57.3, SD 26.5 x 10(9)/L, p < 0.01). There was a wide spectrum of response, the maximal absolute increment ranging from 6.8-69.7 x 10(9)/L (maximal percentage increase 19-863%). Overall there was no relationship between the early increment in reticulocyte count and hemoglobin (Hb) response over the ensuing 4 months. Nine patients became transfusion independent (mean Hb increasing from 6.9, SD 0.8-9.2, SD 1.2 g/dl). Two patients had poor reticulocyte increments and no significant change in Hb. The remaining 5 patients responded partially with a brisk reticulocyte response and a marked reduction in transfusion dependency, but without a sustained increase in Hb. On investigation, all had gastrointestinal bleeding (melena in 1, commencing after initiation of treatment, positive fecal occult bloods in 4), whereas none of the other patients showed evidence of blood loss. It is notable that the erythron was sensitive to this modest dose of rHuEPO in the majority of patients as evidenced by the reticulocyte response. The results provide useful information in the management of patients on rHuEPO. A small or inapparent reticulocyte response suggests a confounding factor; a poor Hb response in the presence of active reticulocyte synthesis points to occult blood loss or hemolysis.

Adult↗
PubMed1995

Re-establishment of erythropoietin responsiveness in end-stage renal failure following renal transplantation.

Re-establishment of erythropoietin (EPO) secretion following renal transplantation is poorly understood. The development of sensitive EPO radioimmunoassay has enabled further study of this phenomenon. Forty-one adult patients were studied during the first 16 weeks following renal transplantation. Twenty six received cyclosporin monotherapy and 15 also received prednisolone and azathioprine. Serum creatinine, haemoglobin (Hb), ferritin and EPO were assayed pre-operatively, daily for 1 week, weekly for 1 month, and fortnightly to 16 weeks. An expected EPO value, for any Hb level, was derived by linear regression analysis in 144 patients with iron deficiency anemia. An observed to expected ratio (O/E) was calculated, a value of 1.0 implying appropriate responsiveness. Hb increased from 8.6 +/- 2.0 (SD) to 12.3 +/- 2.1 g/dl (p < 0.001) over 16 weeks, an increase unaffected by ferritin status. Mean EPO concentration increased during the first week with a peak at day 4 (22.1 +/- 13.3 to 44.6 +/- 40.0 mu/ml, p < 0.05), a change apparent only in patients with immediate graft function (24 cases). There was no correlation between EPO and Hb pre-operatively; however a significant inverse relationship was established by week 16 (r = -0.404, p < 0.02). The median O/E ratio (0.22) at baseline increased progressively to 1.0 at 16 weeks (p < 0.001); ratios were significantly greater in the immediate versus delayed function group throughout (p < 0.05). In the former group an O/E ratio of 1.0 was reached at 10 weeks when mean serum creatinine was 142 +/- 48 mumol/l. Patients with poor ongoing renal function (9 cases, serum creatinine > 250 mumol/l at 16 weeks) had impaired Hb recovery (10.1 +/- 1.6 vs 12.7 +/- 2.0 g/dl at 16 weeks, p < 0.05). EPO values were not different in those patients but median O/E ratios were significantly depressed (p < 0.05) throughout, the maximum O/E ratio being 0.75. Recovery of renal function is accompanied by a beneficial Hb response driven by EPO synthesis in the transplant. The O/E ratio provides a useful index to assess EPO responsiveness. Appropriate secretion was achieved during the first 4 months and optimized by immediate and satisfactory graft function.

Adult↗
PubMed1994

A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system.

We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes. We compared the clearances of substances with a range of molecular weights (MW) in each mode. Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order. All were receiving vancomycin for concurrent sepsis. The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min. Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow. There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05). Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01). For small solutes, the two modalities were equivalent. Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules.

Acute Kidney Injury↗
PubMed1994

Comparison of the use of standard heparin and prostacyclin anticoagulation in spontaneous and pump-driven extracorporeal circuits in patients with combined acute renal and hepatic failure.

Although prostacyclin has been reported to be an effective extracorporeal anticoagulant for intermittent haemofiltration and dialysis treatments, it has been suggested that it is inferior to heparin in preventing clotting in spontaneously driven continuous haemofiltration and/or dialysis circuits. We studied the effectiveness of both heparin and prostacyclin as anticoagulants in a variety of extracorporeal circuits in 17 patients with combined acute hepatic and renal failure who were at risk of haemorrhage. Although there were no differences in the pump-assisted extracorporeal circuits, prostacyclin was found superior to heparin during spontaneously driven continuous arteriovenous haemofiltration and/or dialysis. During some 2,600 h of prostacyclin therapy, there were only 3 episodes of haemorrhage that required blood transfusion compared to 8 major haemorrhages and 2 deaths from intracerebral haemorrhage during 600 h of anticoagulation with heparin. The median filter life was greater with prostacyclin, 60 h (42-72), compared to heparin, 8 h (4-16), p < 0.01. This study suggests that prostacyclin is superior to heparin in maintaining the integrity of a spontaneous arteriovenous extracorporeal circuit in patients at risk of major haemorrhage.

Acute Kidney Injury↗
PubMed1993

Cationic gold staining of glomerular anionic sites in archived tissue, reprocessed from paraffin wax into LR gold resin.

Glomerular capillary wall anionic sites have been demonstrated by cationic gold staining of archived renal biopsy tissue (up to 10 years old), obtained from six patients, originally embedded in paraffin wax, and subsequently reprocessed into LR gold resin. The staining patterns at pH 2.5 and pH 7.0, demonstrating different glomerular basement membrane (GBM) anionic constituents, were compared in three patients from whom tissue directly processed into LR gold and reprocessed tissue was available. Ultrastructural preservation was poorer and shrinkage artefact greater in paraformaldehyde-lysine periodate (PLP) as opposed to formol saline-fixed reprocessed tissue. However, GBM anionic site expression was well preserved, or even enhanced (lamina rara externa, pH 7.0) in reprocessed tissue, using either fixative. Although it may not be possible to compare subtle changes in anionic site distribution in variously fixed and processed tissues, due to these artefacts, the technique enables retrospective study of charge status in archived material from disease groups in which there are distinct anionic site aberrations.

Acrylic Resins↗
PubMed1993

Effect of aluminum mobilization on hemoglobin during the first six months after transplantation.

We prospectively monitored 38 patients for the first six months following successful renal cadaver allograft transplantation. Hemoglobin increased from a mean of 8.2 +/- 0.3 g/dl to 13.4 +/- 0.3 g/dl (SEM), P < 0.001, plasma aluminum decreased from 1.3 +/- 0.2 mumol/liter to 0.46 +/- 0.04 mumol/liter, P < 0.001, and urinary aluminum excretion which peaked at one week post-transplant, 5.5 +/- 1.3 mumol/24 hr decreased to 1.8 +/- 0.3 mumol/24 hr, P < 0.001. Prior to transplantation 22 patients had been prescribed aluminum-containing phosphate binders. Following transplantation this group had persistently greater plasma aluminum and urinary aluminum concentrations which were sustained throughout the study period, compared with those not given aluminum containing medicaments. Hemoglobin and iron status were similar in the two groups prior to transplantation, although red blood cell volume was smaller in those given aluminum-containing phosphate binders, 89 +/- 0.9 fl (fentoliters) versus 95 +/- 1.6 fl, P < 0.05. However, the percentage increase in hemoglobin following transplantation was greater in the group not given aluminum preparations, 34 +/- 4% versus 7 +/- 5% at one month, 69 +/- 7% versus 37 +/- 7% at three months, and 80 +/- 8% versus 56 +/- 8% at six months respectively, all P < 0.05. This study suggests that aluminum mobilization following successful renal transplantation may reduce the rate of hemopoiesis.

Adult↗
PubMed1993

Hypertension in adults with idiopathic glomerulonephritis and normal serum creatinine. A report from the MRC Glomerulonephritis Registry.

The Medical Research Council's Glomerulonephritis Registry was used to determine the prevalence and clinical characteristics of hypertension occurring in patients with idiopathic glomerulonephritis (GN) and normal serum creatinine (males < 120 mumol/l, females < 100 mumol/l). The hypertension prevalence rate was 23.0% in 1221 such patients, increased significantly with age, and within each age group was greater in males than in females. These patterns closely mirror those seen for hypertension in the United Kingdom general population. However, the hypertension prevalence rates in the GN patients significantly exceeded those seen in the corresponding age/sex bands in the general UK population and varied considerably between GN subtypes; thus hypertension in patients with GN and 'near normal' renal function is not solely due to essential hypertension. Logistic regression analysis demonstrated that in addition to increasing age, the presence of hypertension was significantly associated with increased serum creatinine, even in these patients with serum creatinines within the normal range. One possible explanation for these findings may be that people with an inherited tendency to essential hypertension may also be more prone to hypertension if they develop GN. Our data suggests that this early hypertension is closely associated with mild impairment of GFR, occurring within the accepted normal range for serum creatinine.

Adult↗