PubMed HealthSearch

Biomedical subjects

A M Davison

Publications and source records attributed to A M Davison.

At least 19 recordsLinked to original sources

Risk of neoplasia in renal transplant patients.

Renal allograft recipients are at an increased risk of neoplasia, although the extent of the problem has not been established in a typical European transplant population. To assess this risk we did a comprehensive, retrospective study of 918 patients transplanted at one centre over 24 years. The centre (Leeds) serves Yorkshire and Humberside, a region in northern England with a population of 3.6 million. The search, which made use of six sources of information, revealed 70 patients (7.6%) who had developed a neoplastic lesion, 10 patients having more than one type. More than half (42) were cutaneous lesions (mostly squamous cell carcinomas). The risk of developing neoplasia in the first 10 years after transplantation was calculated to be 14%. By 20 years this had risen to 40% compared with a 6% cumulative risk of neoplasia in an age-matched control population (p < 0.005). The full extent of this problem in the European transplant population has been underestimated and, now that recipients are surviving longer, there is a clear need for both lifelong surveillance and closer investigation of these patients.

Adult

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

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

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

Preparation and use of the poly-L-lysine-gold probe: a differential marker of glomerular anionic sites.

The conditions required for the production of a polylysine-coated gold (PL-G) complex, which shows optimal sensitivity for the demonstration of tissue anionic sites, expressed under different conditions of pH have been investigated. Problems encountered with this complex have been compared with those found with other methods of conjugation of polylysine to colloidal gold. The performance of a bovine serum albumin (BSA)-stabilized PL-G complex was examined against other PL-G conjugates, including complexes that are commercially available, for the detection of heterogeneous glomerular anionic site populations, expressed at pH 2.5 and pH 7.0.

Anions

Childhood lymphoma in Yorkshire.

AIMS: A histopathological review of 43 cases of childhood non-Hodgkin's lymphoma (NHL) in an attempt to identify histological variables of prognostic importance. METHOD: Each case was reclassified according to the Working Formulation and an attempt made to allocate an immunophenotype using a panel of monoclonal antibodies. Results were correlated with clinical data on site and survival. RESULTS: Of the 43 cases, 30 were males and 13 females. There were 17 cases of lymphoblastic lymphoma, 15 cases of small non-cleaved cell lymphoma (SNCC), and four cases of large cell lymphoma. The SNCC group was subdivided into 10 cases of Burkitt's lymphoma and five cases of non-Burkitt's lymphoma. An immunophenotype was allocated in 65.1% of cases (23 B, 5 T). The SNCC cases were spread throughout the 0-16 year age range while the lymphoblastic lymphoma cases tended to occur in older children. Most mediastinal tumours were lymphoblastic lymphoma and most abdominal tumours were SNCC. Statistical analysis failed to show a significant difference in survival among histological subgroups or immunophenotypes. CONCLUSION: No histological variables of prognostic importance were identified partly due to the great variation in treatment regimens, standard of supportive care, and prognosis over the period of the study (1972 to 1988).

Adolescent

Blood lactate is reduced following successful treatment of anaemia in haemodialysis patients with recombinant human erythropoietin both at rest and after maximal exertion.

The effect of increasing haemoglobin by erythropoietin therapy on exercise capacity was investigated in 11 regular haemodialysis patients, previously transfusion dependent. Exercise work load increased from a median of 100 W (95% confidence limit, 25-135) to 120 (45-180; p < 0.05) following erythropoietin, and the duration of the exercise test from 13 (3.5-20) to 15.5 min (4-22; p < 0.05). Resting blood lactate concentration decreased from 0.8 (0.6-1.6) to 0.3 mmol/l (0.3-0.4), p < 0.05, following treatment with erythropoietin, as did blood lactate concentration at maximal exertion from 2.0 (1.0-4.1) to 1.8 mmol/l (0.5-2.8; p < 0.05). In association with the increase in haemoglobin from a median of 6 (5.1-6.8) to 11.1 g/dl (11-11.9) following erythropoietin therapy, patients were able to achieve greater exercise capacity both in terms of maximum work load and duration of exercise in association with a reduced resting arterial lactate and a similar exercise-induced lactate production. This suggests that treatment had improved muscle function in terms of lactate production and/or utilisation. This was probably due to the increase in tissue oxygen delivery, as there was an increase in the median arterial oxygen content from 79 (65-85) to 150 ml O2 (144-157) following erythropoietin treatment.

Adult

Use of the urinary protein creatinine index to assess proteinuria in renal transplant patients.

The use of 24-h urine protein collections for the assessment of proteinuria in renal transplant patients has been compared with the protein creatinine index (PCI) obtained from spot urine samples. Paired data from 148 patients showed a correlation of 0.77 (P less than 0.001) between 24-h protein excretion and the PCI. A PCI of 750 identified proteinuria of greater than 1.0 g/24 h with a sensitivity of 89% and a specificity of 93%. The predictive value of a positive test was 81% and that of a negative test 96%. Similar performance was observed for the detection of proteinuria of differing severities ranging from 0.5 g/24 h to 2.0 g/24 h. The use of spot testing was popular with both patients and staff, and reduced the sample handling cost to 15% of that of 24-h urine collection. We recommend that PCI be adopted as the standard outpatient test for the assessment of proteinuria following renal transplantation.

Adolescent

Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry.

The Medical Research Council's Glomerulonephritis Registry was used to study clinicopathological correlations and renal survival in patients with IgA nephropathy reported between 1978 and 1985. IgA nephropathy was the histological diagnosis in 9.3 per cent of all renal biopsies reported to the registry during this period, and in 18.1 per cent of those with a primary glomerulonephritis. The 10-year cumulative renal survival rate accounting for censored data (Kaplan-Meier) was 83.3 per cent. Univariate analysis of survival curves (log-rank test) found the following parameters to be significantly correlated with poor renal survival: serum creatinine > 120 mumol/l (p < 0.001), hypertension (p < 0.001), serum albumin < 40 g/l (p < 0.005), proteinuria > 1 g (p < 0.025), age > 30 years (p < 0.025), and focal mesangial proliferation (p < 0.05). There was no significant difference in renal survival between males and females. Multivariate analysis (Cox's proportional hazards model) revealed that only a serum creatinine of > 120 mumol/l and a serum albumin of < 40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experience of IgA nephropathy and the published European experience. IgA nephropathy is not a benign condition in the UK and patients with impaired renal function and/or those with a reduced serum albumin are significantly more likely to progress to end-stage renal failure within 10 years.

Adult

Cationic colloidal gold--a novel marker for the demonstration of glomerular polyanion status in routine renal biopsies.

Investigations of glomerular anionic charge status in human renal biopsies have previously been restricted, by the techniques and markers used, to staining of sites in pre-embedded tissue. The introduction of a novel marker, cationic colloidal gold, which demonstrates fixed anionic sites in hydrophilic resin (LR Gold)-embedded, ultrathin tissue sections, has now enabled glomerular charge to be evaluated in routine biopsy material. The cationic gold marker detects components which express anionic charge under different pH conditions. The patterns of staining in tissue showing minor glomerular pathology and low proteinuria, together with enzyme-digestion studies indicate that anionic sites are normally associated with heparan sulphate proteoglycans, glycocalyx sialoproteins, hyaluronic acid, and other GBM components which have not yet been characterised. Several charge aberrations involving different pathological mechanisms have been identified using cationic gold. These aberrations may be categorised according to the pathological basis of the charge pattern defect, rather than glomerular disease classification, as a prelude to the precise identification of the anionic sites and their functional importance in relation to the glomerular charge selectivity barrier. The categories which have been defined are: (1) 'Normal', (2) interrupted, (3) neutralised, (4) structurally disorganised, and (5) depleted. As sites are further characterised sub-categorisation is likely. We anticipate that this approach will help to elucidate both the participation of charged components in disease pathogenesis and their role in relation to glomerular proteinuria.

Adolescent